Research ArticleAntihyperlipidemic Activity of Aloe succotrina in RatsPossibly Mediated by Inhibition of HMG-CoA Reductase

Dinesh Dhingra1 Deepak Lamba1 Ramesh Kumar2

Pashupati Nath2 and Satyaprakash Gauttam3

1 Department of Pharmaceutical Sciences Guru Jambheshwar University of Science and Technology Hisar Haryana 125001 India2 Padmnabham Ayurveda Hospital and Research Center 75 Jawahar Nagar Colony Tonk Road Jaipur Rajasthan India3MSM Institute of Ayurveda BPS Mahila Vishwavidyalaya Khanpur Kalan Sonipat Haryana India

Correspondence should be addressed to Dinesh Dhingra din dhingrarediffmailcom

Received 2 October 2013 Accepted 7 November 2013 Published 17 February 2014

Academic Editors G Edwards R Fantozzi T W Stone and S-N Wu

Copyright copy 2014 Dinesh Dhingra et alThis is an open access article distributed under theCreative CommonsAttribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

The present study was designed to investigate antihyperlipidemic activity of dried pulp of Aloe succotrina leaves in Wistar albinorats Hyperlipidemia was induced in rats by feeding them high fat diet (HFD) or D-fructose (25wv) for 4 successive weeksFrom 15th to 28th day dried pulp (100 and 200mgkg po) and atorvastatin (10mgkg po) per se were administered 2 h priorto feeding rats with HFD or fructose Aloe succotrina did not significantly decrease the body weight of rats The dried pulp andatorvastatin per se significantly decreased relative liver weight but did not significantly affect relative heart weight HFD or fructosesignificantly increased serum total cholesterol triglycerides LDL-c and VLDL and decreased HDL-c significantly increased liverMDA and decreased GSH levelsThe dried pulp (200mgkg po) significantly reversed high fat diet-induced and fructose-inducedhyperlipidemia and atherogenic index Aloe succotrina significantly decreased HMG Co-A reductase activity Antihyperlipidemiceffect of the dried pulp was comparable to atorvastatin Thus Aloe succotrina produced significant antihyperlipidemic activity inboth HFD and fructose-induced hyperlipidemic rats possibly through normalization of serum lipid profile HMG-CoA reductaseinhibitory activity and amelioration of oxidative stress in liver

1 Introduction

Hyperlipidemia is a heterogeneous disorder commonly char-acterized by elevated serum total cholesterol low densityand very low-density lipoprotein cholesterol triglyceridesand decreased high-density lipoprotein levels [1] Hyperlipi-demia is one of the greatest risk factors contributing to theprevalence and severity of atherosclerosis and subsequentcoronary heart disease [2] Liver synthesizes two-third of thetotal cholesterol made in the body The rate limiting enzymeis 3-hydroxy-3-methylglutaryl (HMG)-Co A reductase andprovides feedback regulation by controlling the cholesterolconcentrations in cells Treatment of hyperlipidemia involvesdiet control exercise and the use of lipid-lowering diets anddrugs [3]Themost commonly employed drugs for treatmentof hyperlipidemia include hydroxymethylglutarate coenzymeA (HMG-CoA) reductase inhibitors also called as statins

Other drugs employed for treatment of hyperlipidemiainclude bile acid sequestrants (anion-exchange resins) suchas cholestyramine and colestipol fibrates such as clofibrategemfibrozil fenofibrate ciprofibrate and bezafibrate niacincholesterol absorption inhibitors such as ezetimibe andomega-3-fatty acids [4]

In spite of the availability of a number of drugs fortreatment of hyperlipidemia antihyperlipidemic therapy isstill deprived of the efficiency safety and finally ldquocostrdquo Forexample there is a risk of sever muscle damage with statinswhich are particularly well suited for lowering LDL [5]Niacin a good drug for lowering triglycerides may causehyperglycemia and may also cause liver damage [6] Adversereactions of Achilles tendon xanthomas have been reportedafter the addition of niacin and bile acid sequestrants toongoing statin therapy in patients of hypercholesterolemia[7] Adverse effects due to the use of fibrates often relate

Hindawi Publishing CorporationISRN PharmacologyVolume 2014 Article ID 243575 9 pageshttpdxdoiorg1011552014243575

2 ISRN Pharmacology

to the skeletal muscle kidneys or liver Fenofibrate inducedrhabdomyolysis which was complicated with acute renalfailure [8] Thus there is still need for development of betterantihyperlipidemic agents Plant products are frequentlyconsidered to be less toxic and free from side effects thansynthetic ones There are a number of plants reported topossess antihyperlipidemic activity in clinical studies such asAllium sativum [9] Commiphora mukul [10] soy or Glycinemax [11] Nigella sativa [12] and Plantago ovata [13]

Leaves of Aloe succotrina have been reported to possessantimalarial [14] and antidiabetic [15] activities But effectof Aloe succotrina on hyperlipidemia has not been exploredSo the aim of our study was to explore dried pulp of Aloesuccotrina leaves on high fat diet- and fructose-inducedhyperlipidemia in rats

2 Materials and Methods

21 Experimental Animals Wistar albino rats of either sexweighing 60ndash100 g were procured from Disease Free SmallAnimal House Lala Lajpat Rai University of Veterinary andAnimal Sciences Hisar Haryana The animals were housedseparately in groups of 6 per cage (43 times 27 times 15 cm) underlaboratory conditions with alternating light and dark cycleof 12 h each The animals had free access to food and waterThe animals were acclimatized for at least five days beforethe start of experiments The experimental protocol wasapproved by Institutional Animals Ethics Committee andanimal care was taken as per the guidelines of Committee forthe Purpose of Control and Supervision of Experiments onAnimals (CPCSEA) Government of India (Registration no0436)

22 Drugs and Chemicals Atorvastatin (Ranbaxy Labora-tories Ltd Gurgaon) D-fructose cholesterol pure cholicacid egg yolk powder EDTA n-butanol acetic acid trisbuffer hydrochloride sodium lauryl sulphate thiobarbituricacid trichloroacetic acid ethanol carboxy methyl cellulosepotassium chloride Ellmanrsquos reagent (551015840-dithiobis-(2-nitro-benzoic acid) DTNB) pyridine sodium hydroxide sodiumarsenate perchloric acid ferric chloride and hydroxyl aminehydrochloride (HiMedia Laboratories Pvt Ltd Mumbai)were used in the present study

23 Plant Material Dried pulp of Aloe succotrina leaveswas procured from Padmnabham Ayurveda Hospital andResearch Centre Jawahar Nagar Colony Tonk Road Jaipur(Rajasthan India)

24 Vehicle Dried pulp ofAloe succotrina leaves and atorvas-tatin were separately suspended in 1 wv CMC just beforeadministration to the animals

25 Induction of Hyperlipidemia

251 High Fat Diet-Induced Hyperlipidemia High fat dietwas administered for 28 successive days to induce hyperlipi-demia in rats [16] High fat diet consisted of normal feed

(788) cholesterol pure (1) cholic acid (02) lard (10)and egg yolk powder (10) Normal feed contained onlyfreshly cooked dalia (coarsely grounded wheat) Normal andhigh fat diets were freshly prepared each day

252 Fructose-Induced Hyperlipidemia D-fructose (25wv) in drinking water was administered for 28 successivedays to induce hyperlipidemia in rats [24]

26 Experimental Protocol Animals were divided into thefollowing groups and each group comprised of 3ndash6 rats

261 Groups for High Fat Diet Induced-HyperlipidemiaModel

119866119903119900119906119901 1 (119899 = 6) Rats were fed with normal diet for 14successive days From the 15th day to the 28th day vehicleCMC (1wv) was administered orally 2 h before feeding theanimals with normal diet

119866119903119900119906119901 2 (119899 = 6) High fat diet was administered for 14consecutive days From the 15th day to the 28th day vehicleCMC (1wv) was administered orally 2 h before feeding theanimals with high fat diet

119866119903119900119906119901 3 (119899 = 3) High fat diet was administered for 14 con-secutive days From the 15th day to the 28th day atorvastatin(10mgkg po) was administered orally 2 h before feeding theanimals with high fat diet

119866119903119900119906119901119904 4 119886119899119889 5 (119899 = 5 119890119886119888ℎ) High fat diet was admin-istered for 14 consecutive days From the 15th day to the28th day dried pulp of Aloe succotrina leaves (100mgkgand 200mgkg po resp) was administered orally 2 h beforefeeding the animals with high fat diet

262 Groups for Fructose-Induced Hyperlipidemia Model

119866119903119900119906119901 6 (119899 = 5) Rats were fed with normal diet for 14successive days From the 15th day to the 28th day vehicleCMC (1wv) was administered orally 2 h before feeding theanimals with normal diet

119866119903119900119906119901 7 (119899 = 5) Fructose (25wv) was administered for 14consecutive days From the 15th day to the 28th day vehicleCMC (1wv) was administered orally 2 h before feeding theanimals with fructose (25 wv)

119866119903119900119906119901 8 (119899 = 5) Fructose (25 wv) was administeredfor 14 consecutive days From the 15th day to the 28thday atorvastatin (10mgkg po) was administered orally 2 hbefore feeding the animals with fructose solution

119866119903119900119906119901119904 9 119886119899119889 10 (119899 = 5 119890119886119888ℎ) Fructose (25 wv) wasadministered for 14 consecutive days From the 15th day tothe 28th day dried pulp of Aloe succotrina leaves (100mgkgand 200mgkg po resp) was administered orally 2 h beforefeeding the animals with fructose solution

ISRN Pharmacology 3

27 Measurement of Body Weight Relative Liver and HeartWeight of Rats Body weights of animals of all groups weremeasured every week But relative liver and heart weight ofthe animals were measured on the 29th day after sacrificingthe animals Relative liver and heart weight were calculatedby applying the following formula [17]

Relative weight = (Organ weightBody weight

) times 100 (1)

28 Biochemical Estimations in Serum On day 29 animalswere sacrificed by carotid artery bleeding under light anesthe-sia with diethyl ether and blood samples (about 05mL fromeach animal) were collected Blood was kept for 30min forcoagulation and then serum was separated by centrifugationat 3000 rpm using centrifuge (Remi Mumbai) Total choles-terol [18] HDL-cholesterol [19] and triglycerides [20] weremeasured in serum samples using commercially biochemicalkits (Erba Diagnostics Mannheim Germany) The sampleswere analyzed by using semiautomatic autoanalyzer (Chem 5plus-V

2autoanalyzer Erba Mannheim Germany)

29 Biochemical Estimations in Liver Homogenate

291 Estimation of Reduced Glutathione (GSH) LevelsReduced glutathione levels were measured in liverhomogenate by using the procedure as reported earlier[21] The tissue sample (200mg of liver) was homogenizedin 80mL of 002M EDTA in an ice bath The homogenateswere kept in the ice bath until used Aliquots of 50mL ofthe homogenates were mixed in 150mL test tubes with40mL distilled water and 10mL of 50 trichloroaceticacid (TCA) The tubes were centrifuged for 15min at3000 rpm The supernatant (20mL) was mixed with 40mLof 04M Tris buffer (pH 89) followed by addition of01mL Ellmanrsquos reagent [55-dithiobis-(2-nitrobenzoicacid)]and the sample was shaken The absorbance was readwithin 5min of the addition of DTNB at 412 nm against areagent blank with no homogenate using double beam UV-Visible spectrophotometer (Varian Cary 5000 UV-VIS-NIRSpectrophotometer The Netherland)

292 Estimation of Malondialdehyde Levels Malondialde-hyde (MDA) an index of free radical generationlipid per-oxidation was measured in liver homogenate by using theprocedure as reported earlier [22] The tissue sample (100mgof liver) was homogenized in 90mL of KCL Briefly thereaction mixture consisted of 02mL of 81 sodium laurylsulphate 15mL of 20 acetic acid (pH 35) and 15mL of08 aqueous solution of thiobarbituric acid added to 02mLof liver homogenate The mixture was made up to 40mLwith distilled water and heated at 95∘C for 60min Aftercooling the contents under running tap water 50mL of n-butanol and pyridine (15 1 vv) and 10mL of distilled waterwere addedThe contents were centrifuged at about 4000 rpmfor 10min The organic layer was separated out and itsabsorbance was measured at 532 nm using double beam UV-Visible spectrophotometer (Varian Cary 5000 UV-VIS-NIR

SpectrophotometerThe Netherland) against a reagent blankMDA values were calculated using the extinction coefficientof MDA-thiobarbituric acid complex 156 times 105 lmol times cmand expressed as nmolmg tissue

293 Estimation of HMG-CoA Reductase Activity (HMG-CoAMevalonate Ratio) HMG-CoA reductase activity wasmeasured in liver homogenate using the procedure of Venu-gopala Rao and Ramakrishnan [23] The ratio of HMG-CoAtomevalonate was taken as an index of enzyme activity whichcatalyzes the conversion of HMG to mevalonate The lowerthe ratio the higher the enzyme activity The liver sample(100mg) was homogenized in 10mL of arsenate (1 gmL)solution Equal volumes (05mL each) of fresh liver 10tissue homogenate and diluted perchloric acid (50mLL)were mixed together This was allowed to stand for 5 minuteand centrifuged at about 2000 rpm for 10min This wasfiltered and 1mL of filtrate was mixed with 05mL of freshlyprepared hydroxyl amine (2molL) reagent of pH 55 forHMG-CoA and with 05mL of freshly prepared hydroxylamine (2molL) reagent of pH 21 for mevalonate After5 minutes 15mL of ferric chloride reagent (prepared bydissolving 52 gm of trichloroacetic acid and 10 gm of ferricchloride in 50mL of 065molL HCl) was added to each ofthe test tube for HMG-CoA and mevalonate The tubes wereshaken well Absorbance was read after 10min at 540 nmversus a similarly treated arsenate blank using double beamUV-Visible spectrophotometer (Varian Cary 5000 UV-VIS-NIR Spectrophotometer The Netherland)

210 Statistical Analysis All values were expressed as meanplusmn SEM The data were statistically analyzed using one-wayANOVA followed by Tukey-Kramer multiple comparisontest The 119875 lt 005 was considered to be statisticallysignificant

3 Results

31 Effects of Dried Pulp of Aloe succotrina Leaves on High FatDiet-Induced Hyperlipidemic Rats

311 Effect of Aloe succotrina on Body Weight High fatdiet significantly increased the body weight as compared tovehicle treated control after 2 weeks of treatment and thisincrease in body weight continued up to 4 weeks Dried pulpof Aloe succotrina leaves (100mg and 200mgkg po) andatorvastatin per se administered from the 15th day to the 28thday did not significantly decrease the body weights of high fatdiet-induced hyperlipidemic rats at the 3rd and 4th weeks oftreatment as compared to their respective high fat diet control(Table 1)

312 Effect of Aloe succotrina on Relative Liver and HeartWeight High fat diet significantly increased the relative liverweight of rats but did not significantly increase the relativeheart weight of animals as compared to vehicle treated controlafter 28 days Dried pulp of Aloe succotrina leaves (100mgand 200mgkg po) and atorvastatin (10mgkg po) per se

4 ISRN Pharmacology

Table 1 Effect of dried pulp of Aloe succotrina leaves on body weight of HFD-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Numberof animals

Body weight (g)Week 0 Week 1 Week 2 Week 3 Week 4

1 Vehicle(1wvCMC) 10mL 6 8316 plusmn 398 8766 plusmn 409 955 plusmn 377 10333 plusmn 482 10433 plusmn 478

2Vehicle

(1wvCMC)+ HFD

10mL 6 8233 plusmn 296 10216 plusmn 319a11266 plusmn 473

c12966 plusmn 590

c13600 plusmn 575

c

3 Atorvastatin +HFD 10mg 3 8300 plusmn 444 9816 plusmn 516 11816 plusmn 837 12400 plusmn 809 13333 plusmn 1186

4 Aloe succotrina+ HFD 100mg 5 7916 plusmn 392 10183 plusmn 5134 1245 plusmn 574 10666 plusmn 548 1158 plusmn 1633

5 Aloe succotrina+ HFD 200mg 5 8183 plusmn 513 10400 plusmn 717 12983 plusmn 825 13883 plusmn 698 1506 plusmn 736

In each group values are in Mean plusmn SEM data were analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 25) = 2129 119875 lt 00001 (for HFD treated control from week 0 to week 4)F (4 25) = 1636 119875 lt 01964 (comparison among various groups at week 1)F (4 25) = 4207 119875 lt 00097 (comparison among various groups at week 2)F (4 25) = 5585 119875 lt 00024 (comparison among various groups at week 3)F (4 20) = 7901 119875 lt 00005 (comparison among various groups at week 4)a119875 lt 005 and c

119875 lt 0001 as compared to HFD treated control (week 0)

Table 2 Effect of dried pulp of Aloe succotrina leaves on relative liver and heart weight of HFD-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Number of animals Relative organ weightLiver weight Heart weight

1 Vehicle (1wvCMC) 10mL 6 498 plusmn 032 063 plusmn 007

2 Vehicle (1wvCMC) + HFD 10mL 6 780 plusmn 054

070 plusmn 004

3 Atorvastatin + HFD 10mg 3 577 plusmn 031a

059 plusmn 006

4 Aloe succotrina + HFD 100mg 5 687 plusmn 032 064 plusmn 004

5 Aloe succotrina + HFD 200mg 5 581 plusmn 034a

060 plusmn 002

Relative weight = (organ weightbody weight) times 100 Values are in Mean plusmn SEM data were analyzed by one-way ANOVA followed by Tukey-Kramer multiplecomparison testF (4 20) = 8271 119875 lt 00004 (for relative liver weight)F (4 20) = 0747 119875 lt 05715 (for relative heart weight)119875 lt 0001 as compared to vehicle treated control a119875 lt 005 as compared to HFD treated control

administered from the 15th day to the 28th day significantlydecreased relative liver weight as compared to high fat dietcontrol on the 29th day (Table 2) but did not significantlyaffect relative heart weight (Table 2)

313 Effect of Aloe succotrina on Serum Lipid ParametersHigh fat diet significantly increased serum triglyceridestotal cholesterol LDL-c VLDL and atherogenic index andsignificantly decreased HDL-cholesterol levels as comparedto vehicle treated control Dried pulp of Aloe succotrinaleaves (200mgkg po) and atorvastatin (10mgkg) per sesignificantly decreased serum total cholesterol triglyceridesVLDL LDL-c and atherogenic index and increased HDL-cholesterol levels as compared to high fat diet control Lowerdose (100mgkg) of dried pulp of Aloe succotrina leavessig-nificantly decreased serum total cholesterol and LDL-c andincreased HDL-cholesterol levels but did not significantlyaffect TG VLDL and atherogenic index as compared to highfat diet control (Table 3)

314 Effect of Aloe succotrina on Liver HMGMevalonateRatio Malondialdehyde (MDA) and Reduced Glutathione(GSH) Levels High fat diet significantly increased MDA lev-els and decreased GSH levels as compared to vehicle treatedcontrol Dried pulp of Aloe succotrina leaves (200mgkg po)and atorvastatin (10mgkg) per se significantly increasedHMGmevalonate ratio (or decreased HMG-CoA reductaseactivity) decreased MDA levels and increased GSH levels ascompared to high fat diet control Lower dose (100mgkg)of dried pulp of Aloe succotrina leaves significantly decreasedMDA levels and did not significantly affect GSH and HMG-CoA reductase activity as compared to high fat diet control(Table 4)

32 Effect of Dried Pulp of Aloe succotrina Leaves on Fructose-Induced Hyperlipidemic Rats

321 Effect of Aloe succotrina on Body Weight Fructose(25 wv) dried pulp of Aloe succotrina leaves (100mg and200mgkg po) and atorvastatin (10mgkg po) per se did

ISRN Pharmacology 5

Table 3 Effect of dried pulp of Aloe succotrina leaves on serum lipid levels in HFD-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Lipid levels (mgdL)

TC TG HDL-c VLDL LDL-c AI(TGHDL)

1Vehicle

(1wvCMC)(119899 = 6)

10mL 7824 plusmn 408 1955 plusmn 504 3718 plusmn 045 391 plusmn 101 3699 plusmn 464 028 plusmn 007

2Vehicle

(1wvCMC)+ HFD (119899 = 6)

10mL 31542 plusmn 2717 10804 plusmn 1167 1738 plusmn 397 2160 plusmn 234 27640 plusmn 2638 1057 plusmn 386

3 Atorvastatin +HFD (119899 = 3) 10mg 15606 plusmn 2065c 2842 plusmn 665

b5037 plusmn 367

c568 plusmn 133

b10000 plusmn 2036

c055 plusmn 009

a

4 Aloe succotrina+ HFD (119899 = 5) 100mg 23132 plusmn 2200a 9490 plusmn 2138 3394 plusmn 330

b1898 plusmn 428 17845 plusmn 2240

b284 plusmn 063

5 Aloe succotrina+ HFD (119899 = 5) 200mg 18130 plusmn 1226c 4834 plusmn 966

a4765 plusmn 124

c967 plusmn 193

a12398 plusmn 1170

c102 plusmn 022

a

Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison test TCmdashtotal cholesterol TGmdashtriglycerides HDL-cmdashhigh density lipoprotein-cholesterol LDL-cmdashlow density lipoprotein-cholesterol VLDLmdashvery low density lipoprotein- cholesterolAImdashatherogenic indexF (4 20) = 25856 119875 lt 00001 (for total cholesterol)F (4 20) = 10308 119875 lt 00001 (for triglycerides)F (4 20) = 21007 119875 lt 00001 (for HDL-c)F (4 20) = 10297 119875 lt 00001 (for VLDL)F (4 20) = 27085 119875 lt 00001 (for LDL-c)F (4 20) = 4623 119875 lt 00083 (for AI)119875 lt 005 and

119875 lt 0001 as compared to vehicle treated control a119875 lt 005 b119875 lt 001 and c119875 lt 0001 as compared to HFD treated control

Table 4 Effect of dried pulp of Aloe succotrina leaves on liver HMGmevalonate ratio malondialdehyde (MDA) and reduced glutathione(GSH) levels of HFD-induced hyperlipidemic rats

Groupnumber Treatment (po) Dose (kgminus1) Number of animals HMGmevalonate

ratioMDA levels

(nmolmg tissue)GSH levels

(120583molmg tissue)

1 Vehicle(1wvCMC) 10mL 6 059 plusmn 023 5260 plusmn 1049 73521 plusmn 5731

2Vehicle

(1wvCMC) +HFD

10mL 6 037 plusmn 013 17974 plusmn 237729762 plusmn 2481

3 Atorvastatin + HFD 10mg 3 329 plusmn 037c

1343 plusmn 465c

66584 plusmn 2434c

4 Aloe succotrina +HFD 100mg 5 081 plusmn 013 7856 plusmn 2766

b30384 plusmn 3185

5 Aloe succotrina +HFD 200mg 5 168 plusmn 034

b5272 plusmn 1232

c61786 plusmn 2635

c

Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 20) = 14402 119875 lt 00001 (for HMGmevalonate ratio)F (4 20) = 10117 119875 lt 00001 (for MDA levels)F (4 20) = 25390 119875 lt 00001 (for reduced glutathione levels)119875 lt 001 and

119875 lt 0001 as compared to vehicle treated control b119875 lt 005 and c119875 lt 0001 as compared to HFD treated control

not significantly affect the body weight of rats as compared tovehicle treated control (Table 5)

322 Effect of Aloe succotrina on Relative Liver and HeartWeight Fructose (25 wv) significantly increased the rel-ative liver weight of animals but did not significantly increasethe relative heart weight of animals as compared to vehicletreated control after 28 days Dried pulp of Aloe succot-rina leaves (100mg and 200mgkg po) and atorvastatin(10mgkg po) per se significantly decreased relative liverweight of animals as compared to fructose treated control but

did not significantly affect relative heart weight of animals(Table 6)

323 Effect of Aloe succotrina on Serum Lipid Parame-ters Fructose (25 wv) significantly increased serum totalcholesterol triglycerides VLDL LDL-c and atherogenicindex and significantly decreased HDL-cholesterol levels ascompared to vehicle treated control Dried pulp of Aloesuccotrina leaves (200mgkg po) and atorvastatin (10mgkgpo) per se significantly decreased serum total cholesteroltriglycerides VLDL LDL-c and atherogenic index and

6 ISRN Pharmacology

Table 5 Effect of dried pulp of Aloe succotrina leaves on body weight of fructose-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Body weight (g)Week 0 Week 1 Week 2 Week 3 Week 4

1 Vehicle(1wvCMC)0 10mL 8066 plusmn 439 8383 plusmn 543 9400 plusmn 497 10233 plusmn 469 11416 plusmn 552

2Vehicle

(1wvCMC) +fructose (25wv)

10mL 8116 plusmn 735 8816 plusmn 900 9200 plusmn 1034 9516 plusmn 1042 10683 plusmn 1108

3 Atorvastatin +fructose (25wv) 10mg 7866 plusmn 354 8683 plusmn 433 9566 plusmn 475 10283 plusmn 352 11316 plusmn 309

4 Aloe succotrina +fructose (25wv) 100mg 8316 plusmn 540 9166 plusmn 719 9983 plusmn 704 9683 plusmn 656 1068 plusmn 950

5 Aloe succotrina +fructose (25wv) 200mg 8083 plusmn 447 865 plusmn 613 9616 plusmn 550 10600 plusmn 444 11916 plusmn 614

(119899 = 5) in each group Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 25) = 095 119875 lt 004516 (for fructose treated control from week 0 to week 4)F (4 25) = 019 119875 lt 09431 (comparison among various groups at week 1)F (4 25) = 018 119875 lt 09464 (comparison among various groups at week 2)F (4 25) = 049 119875 lt 07422 (comparison among various groups at week 3)F (4 25) = 049 119875 lt 07432 (comparison among various groups at week 4)

Table 6 Effect of dried pulp of Aloe succotrina leaves on relative liver and heart weight of fructose-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Relative organ weightLiver weight Heart weight

1 Vehicle (1wvCMC) 10mL 348 plusmn 015 040 plusmn 001

2 Vehicle (1wvCMC) + fructose (25wv) 10mL 578 plusmn 074

042 plusmn 002

3 Atorvastatin + fructose (25wv) 10mg 387 plusmn 036a

047 plusmn 003

4 Aloe succotrina + fructose (25wv) 100mg 392 plusmn 030a

046 plusmn 002

5 Aloe succotrina + fructose (25wv) 200mg 387 plusmn 029a

049 plusmn 003

Relative weight = (organ weightbody weight) times 100(119899 = 5) in each group Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 21) = 4742 119875 lt 0007 (for relative liver weight)F (4 21) = 1594 119875 lt 01045 (for relative heart weight)119875 lt 001 as compared to vehicle treated control a119875 lt 005 as compared to fructose treated control

increased HDL-cholesterol levels as compared to fructosetreated control on the 29th day Lower dose (100mgkg) ofthe dried pulp significantly decreased serum triglyceridesVLDL and atherogenic index but did not significantly affecttotal cholesterol LDL-c and HDL-c as compared to fructosetreated control (Table 7)

324 Effect of Aloe succotrina on Liver HMGMevalonateRatio Malondialdehyde (MDA) and Reduced Glutathione(GSH) Levels Fructose (25wv) diet significantly increasedMDA and decreased GSH levels as compared to vehi-cle treated control Dried pulp of Aloe succotrina leaves(200mgkg po) and atorvastatin (10mgkg) per se signifi-cantly increased HMGmevalonate ratio and GSH levels anddecreased MDA levels as compared to fructose treated con-trol Lower dose (100mgkg) of the dried pulp significantlydecreased MDA levels but did not significantly affect GSHand HMG-CoA reductase activity as compared to fructosetreated control (Table 8)

4 Discussion

In the present study dried pulp of Aloe succotrina leavesproduced significant antihyperlipidemic effect in high fatdiet- and fructose-induced hyperlipidemic rats Rats fed withHFD or fructose for 4 successive weeks induced significanthyperlipidemia as indicated by the significant increase inserum levels of TC TG LDL-c and VLDL and decrease inserum levels of HDL-c This is supported by earlier studies[17 24 25] High fat diet had unfavorable effect on bodyweight and relative liver weight but did not significantly affectrelative heart weightThis is supported by earlier study whereHFD increased body weight and relative liver weight withoutsignificantly affecting relative heart weight [26] D-fructose(25 wv) produced increase in relative liver weight withoutsignificantly affecting body weight and relative heart weightof animals This result is also supported by the literature [17]

Fructose has been reported to induce hypertriglyc-eridemia associated with insulin resistance hyperinsuline-mia and hypertension After the absorption in GIT fructose

ISRN Pharmacology 7

Table 7 Effect of the dried pulp of Aloe succotrina leaves on serum lipid levels in fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Lipid Levels (mgdL)

TC TG HDL-c VLDL LDL-c AI(TGHDL)

1 Vehicle(1wvCMC) 10mL 6709 plusmn 274 3947 plusmn 175 3726 plusmn 183 793 plusmn 037 2183 plusmn 454 107 plusmn 006

2

Vehicle(1wvCMC)+ fructose(25wv)

10mL 8556 plusmn 437 6710 plusmn 1269 1736 plusmn 149 1342 plusmn 254 5480 plusmn 603 393 plusmn 074

3Atorvastatin +

fructose(25wv)

10mg 6432 plusmn 409a 2259 plusmn 214c 4172 plusmn 606b 452 plusmn 043c1809 plusmn 489

b060 plusmn 010

c

4Aloe succotrina+ fructose(25wv)

100mg 7197 plusmn 612 3322 plusmn 398b 4233 plusmn 548 664 plusmn 080b3853 plusmn 694 142 plusmn 032

c

5Aloe succotrina+ fructose(25wv)

200mg 6615 plusmn 216a 2474 plusmn 244c 2680 plusmn 471b 495 plusmn 049c1887 plusmn 527

b062 plusmn 009

c

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testTCmdashtotal cholesterol TGmdashtriglycerides HDL-cmdashhigh density lipoprotein- cholesterolLDL-cmdashlow density lipoprotein- cholesterol VLDLmdashvery low density lipoprotein- cholesterol AImdashatherogenic indexF (4 21) = 4344 119875 lt 00109 (for total cholesterol) F (4 21) = 8425 119875 lt 00004 (for triglycerides) F (4 21) = 6170 119875 lt 00021 (for HDL-c) F (4 21) = 8414119875 lt 00004 (for VLDL) F (4 21) = 8118 119875 lt 00005 (for LDL-c) F (4 21) =14361 119875 lt 00001 (for AI)119875 lt 005 119875 lt 001 and

119875 lt 0001 as compared to vehicle treated control a119875 lt 005 b119875 lt 001 and c119875 lt 0001 as compared to fructose treated control

Table 8 Effect of dried pulp ofAloe succotrina leaves on liverHMGmevalonate ratioMDA and reduced glutathione (GSH) levels of fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

HMGmevalonateratio

MDA levels (nmolmgtissue)

GSH levels (120583molmgtissue)

1 Vehicle(1wvCMC) 10mL 344 plusmn 122 764 plusmn 156 52455 plusmn 3589

2Vehicle

(1wvCMC) +fructose (25wv)

10mL 198 plusmn 036 4902 plusmn 092

31720 plusmn 1940

3 Atorvastatin +fructose (25wv) 10mg 617 plusmn 093

a692 plusmn 069

c44574 plusmn 1957

a

4 Aloe succotrina +fructose (25wv) 100mg 375 plusmn 078 3166 plusmn 833

a32404 plusmn 1331

5 Aloe succotrina +fructose (25wv) 200mg 566 plusmn 067

a885 plusmn 205

c42813 plusmn 3429

a

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 21) = 4140 119875 lt 00001 (for HMGmevalonate ratio)F (4 21) = 7607 119875 lt 00007 (for MDA levels)F (4 21) = 11289 119875 lt 00001 (for reduced glutathione)119875 lt 0001 as compared to vehicle treated control

a119875 lt 005 b119875 lt 005 and c

119875 lt 0001 as compared to fructose treated control

is transported via portal circulation to the liver whereit enters hepatocytes via the glucose transporter GLUT-5independently of insulin and is rapidly metabolised Fruc-tose is metabolised into ldquoglycerol-3-phosphaterdquo and ldquoacetylCoArdquo These two intermediate metabolites are then used assubstrates for glycerides synthesis contributing to VLDL-TG production in liver The exposure of liver to suchlarge quantities of fructose leads to rapid stimulation oflipogenesis and triglyceride accumulation which in turncontributes to reduced insulin sensitivity and hepatic insulinresistanceglucose intolerance [25 27]

In both HFD and fructose-induced hyperlipidemia mod-els dried pulp of Aloe succotrina leaves (200mgkg po)significantly decreased total cholesterol triglycerides LDL-c VLDL atherogenic index and liver weight and increasedHDL-c levels Antihyperlipidemic effect of the dried pulp wascomparable to atorvastatin a standard antihyperlipidemicdrug (a HMG-CoA reductase inhibitor)

Hyperlipidemia is thought to increase cholesterol con-tent and this in turn leads to generation of reactive oxy-gen species (ROS) increase in lipid peroxidation [28] anddecrease in activity of reduced glutathione It has been

8 ISRN Pharmacology

reported that overproduction of ROS can induce cellulardamage via oxidation of critical cellular components suchas membrane lipids proteins and DNA [29] The increasedlevels of total cholesterol in blood could induce arterialendothelial dysfunction and vascular endothelial injury isthe initial factor in atherosclerosis Therefore lowering lipidand protecting vascular endothelium play significant roles inpreventing atherosclerosis [30]

Previous studies showed that high fat diet [31] or fructose[25] enhanced hepatic oxidative damage due to hepaticstress resulting from the burden of high fat diet or fructosemetabolism In the present study HFD or fructose signifi-cantly increased liver MDA levels and decreased GSH levelsindicating enhancement of oxidative stressThese findings arein agreement with earlier reports [32] Dried pulp of Aloesuccotrina leaves (200mgkg) significantly increased liverGSH levels and decreased MDA levels in both HFD andfructose-induced hyperlipidemic rats thus reduced oxidativestress

To identify the possible mechanism of the antihyper-lipidemic effect of the dried pulp more specifically theactivity of HMG-CoA reductase was determined Cholesterolhomeostasis is maintained by the two processes namelycholesterol biosynthesis in which HMG-CoA reductase cat-alyzes rate limiting process and cholesterol absorption ofboth dietary cholesterol and cholesterol cleared from the liverthrough biliary secretion [33] The HMG-CoAmevalonateratio has an inverse relationship to the activity HMG-CoAreductase The result of the present study indicated that theactivity of HMG-CoA reductase is significantly inhibited bythe dried pulp of Aloe succotrina leaves (200mgkg) in bothHFD and fructose-induced hyperlipidemic rats

Hyperlipidemia is awell-known risk factor for atheroscle-rosis which is a major contributor to the pathogenesis ofheart and vascular diseases Elevated blood concentrationof cholesterol especially in LDL-c constitutes the key riskfactor for atherosclerosis [34] Atherogenic index indicatesthe deposition of foam cells or plaque or fatty infiltrationor lipids in heart coronaries aorta liver and kidneys Thehigher the atherogenic index the higher the risk of theabove organs for oxidative damage [35]Aloe succotrina leaves(200mgkg) also markedly lowered atherogenic index inboth HFD and fructose-induced hyperlipidemic rats Thusit indicated its potential in preventing atherosclerosis

5 Conclusions

Dried pulp of Aloe succotrina leaves produced significantantihyperlipidemic activity in both HFD and fructose-induced hyperlipidemic rats possibly through normalizationof serum lipid profile HMG-CoA reductase inhibitory activ-ity and amelioration of oxidative stress in liver Moreoverit also significantly decreased atherogenic index thus itmight possess potential in preventing atherosclerosis Furtherstudies are required to isolate the active constituents involvedin antihyperlipidemic activity of Aloe succotrina Thus driedpulp ofAloe succotrina leavesmay be explored for its potentialin the prevention and treatment of clinical hyperlipidemia

Conflict of Interests

Theauthors do not have any conflict of interests regarding thecontent of this research paper

Acknowledgment

The authors are thankful to Ranbaxy Laboratories PvtLtd Gurgaon (Haryana India) for providing gift sample ofatorvastatin

References

[1] G D Kolovou K K Anagnostopoulou and D V CokkinosldquoPathophysiology of dyslipidaemia in themetabolic syndromerdquoPostgraduate Medical Journal vol 81 no 956 pp 358ndash3662005

[2] R M Krauss and Y A Kesaniemi ldquoCardiovascular disease andhyperlipidaemiardquo Current Opinion in Lipidology vol 5 no 4pp 249ndash251 1994

[3] N J Stone ldquoLipidmanagement current diet and drug treatmentoptionsrdquo The American Journal of Medicine vol 101 no 4supplement 1 pp 40Sndash49S 1996

[4] Y Lin S S Mousa N Elshourbagy and S A Mousa ldquoCurrentstatus and future directions in lipid management emphasiz-ing low-density lipoproteins high-density lipoproteins andtriglycerides as targets for therapyrdquo Vascular Health and RiskManagement vol 6 no 1 pp 73ndash85 2010

[5] M Kobayashi T Kagawa K Narumi S Itagaki T Hiranoand K Iseki ldquoBicarbonate supplementation as a preventive wayin statins-induced muscle damagerdquo Journal of Pharmacy andPharmaceutical Sciences vol 11 no 1 pp 1ndash8 2008

[6] J R Guyton and H E Bays ldquoSafety considerations with niacintherapyrdquoThe American Journal of Cardiology vol 99 no 6 ppS22ndashS31 2007

[7] W C Lakey N Greyshock and J R Guyton ldquoAdverse reactionsof Achilles tendon xanthomas in three hypercholesterolemicpatients after treatment intensification with niacin and bile acidsequestrantsrdquo Journal of Clinical Lipidology vol 7 no 2 pp 178ndash181 2013

[8] M Kiskac M Zorlu M Cakirca et al ldquoA case of rhabdomy-olysis complicated with acute renal failure after resumption offenofibrate therapy a first reportrdquo Indian Journal of Pharmacol-ogy vol 45 no 3 pp 305ndash306 2013

[9] Y-Y Yeh and L Liu ldquoCholesterol-lowering effect of garlicextracts and organosulfur compounds human and animalstudiesrdquo Journal of Nutrition vol 131 no 3 pp 989Sndash993S 2001

[10] R B Singh M A Niaz and S Ghosh ldquoHypolipidemic andantioxidant effects of commiphora mukul as an adjunct todietary therapy in patients with hypercholesterolemiardquo Cardio-vascular Drugs andTherapy vol 8 no 4 pp 659ndash664 1994

[11] W W Wong E OrsquoBrian Smith J E Stuff D L Hachey WC Heird and H J Pownell ldquoCholesterol-lowering effect ofsoy protein in normocholesterolemic and hypercholesterolemicmenrdquoThe American Journal of Clinical Nutrition vol 68 no 6pp 13855Sndash13895S 1998

[12] A M Sabzghabaee M Dianatkhah N Sarrafzadegan SAsgary and A Ghannadi ldquoClinical evaluation of Nigella sativaseeds for the treatment of hyperlipidemia a randomizedplacebo controlled clinical trialrdquo Medical Archives vol 66 no3 pp 198ndash200 2012

ISRN Pharmacology 9

[13] R Sola E Bruckert R-M Valls et al ldquoSoluble fibre (Plantagoovata husk) reduces plasma low-density lipoprotein (LDL)cholesterol triglycerides insulin oxidised LDL and systolicblood pressure in hypercholesterolaemic patients a randomisedtrialrdquo Atherosclerosis vol 211 no 2 pp 630ndash637 2010

[14] R L Van Zyl and A M Viljoen ldquoIn vitro activity of Aloeextracts against Plasmodium falciparumrdquo South African Journalof Botany vol 68 no 1 pp 106ndash110 2002

[15] D K Patel R Kumar D Laloo and S Hemalatha ldquoNaturalmedicines from plant source used for therapy of diabetesmellitus an overview of its pharmacological aspectsrdquo pp 239ndash250 2012

[16] B Lu D Xia W Huang X Wu Y Zhang and Y YaoldquoHypolipidemic effect of bamboo shoot oil (P pubescens) inSprague-Dawley ratsrdquo Journal of Food Science vol 75 no 6 ppH205ndashH211 2010

[17] N Taleb-Dida D Krouf and M Bouchenak ldquoGlobulariaalypum aqueous extract decreases hypertriglyceridemia andameliorates oxidative status of the muscle kidney and heart inrats fed a high-fructose dietrdquo Nutrition Research vol 31 no 6pp 488ndash495 2011

[18] C C Allain L S Poon and C S G Chan ldquoEnzymaticdetermination of total serum cholesterolrdquo Clinical Chemistryvol 20 no 4 pp 470ndash475 1974

[19] M Burstein H R Scholnick and RMorfin ldquoRapidmethod forthe isolation of lipoproteins fromhuman serumby precipitationwith polyanionsrdquo Journal of Lipid Research vol 11 no 6 pp583ndash595 1970

[20] MWMcGowan J D Artiss D R Strandbergh and B Zak ldquoAperoxidase-coupledmethod for the colorimetric determinationof serum triglyceridesrdquo Clinical Chemistry vol 29 no 3 pp538ndash542 1983

[21] J Sedlak and R H Lindsay ldquoEstimation of total protein-bound andnonprotein sulfhydryl groups in tissuewith Ellmanrsquosreagentrdquo Analytical Biochemistry vol 25 pp 192ndash205 1968

[22] H Ohkawa N Ohishi and K Yagi ldquoAssay for lipid peroxidesin animal tissues by thiobarbituric acid reactionrdquo AnalyticalBiochemistry vol 95 no 2 pp 351ndash358 1979

[23] A Venugopala Rao and S Ramakrishnan ldquoIndirect assessmentof hydroxymethylglutaryl CoA reductase (NADPH) activity inliver tissuerdquo Clinical Chemistry vol 21 no 10 pp 1523ndash15251975

[24] A R Borate A A Suralkar S S Birje P V Malusare and PA Bangale ldquoAntihyperlipidemic effect of protocatechuic acid infructose induced hyperlipidemia in ratsrdquo International Journalof Pharma and Bio Sciences vol 2 no 4 pp 456ndash460 2011

[25] G L Kelley G Allan and S Azhar ldquoHigh dietary fructoseinduces a hepatic stress response resulting in cholesterol andlipid dysregulationrdquo Endocrinology vol 145 no 2 pp 548ndash5552004

[26] J Fu X Zhang K Liu et al ldquoHypolipidemic activity in Sprague-Dawley rats and constituents of a novel natural vegetable oilfrom Cornus wilsoniana fruitsrdquo Journal of Food Science vol 77pp 160ndash169 2012

[27] O-J Park D Cesar D Faix K Wu C H L Shackleton andM K Hellerstein ldquoMechanisms of fructose-induced hyper-triglyceridaemia in the rat Activation of hepatic pyruvatedehydrogenase through inhibition of pyruvate dehydrogenasekinaserdquo Biochemical Journal vol 282 no 3 pp 753ndash757 1992

[28] R Yazdanparast S Bahramikia and A Ardestani ldquoNasturtiumofficinale reduces oxidative stress and enhances antioxidant

capacity in hypercholesterolaemic ratsrdquo Chemico-BiologicalInteractions vol 172 no 3 pp 176ndash184 2008

[29] P G Jain S D Patil N G Haswani M V Girase and SJ Surana ldquoHypolipidemic activity of Moringa oleifera LamMoringaceae on high fat diet induced hyperlipidemia in albinoratsrdquoBrazilian Journal of Pharmacognosy vol 20 no 6 pp 969ndash973 2010

[30] MValgimigli EMerli PMalagutti et al ldquoEndothelial dysfunc-tion in acute and chronic coronary syndromes evidence for apathogenetic role of oxidative stressrdquo Archives of Biochemistryand Biophysics vol 420 no 2 pp 255ndash261 2003

[31] N P Visavadiya and A V R L Narasimhacharya ldquoHypolipi-demic and antioxidant activities of Asparagus racemosus inhypercholesteremic ratsrdquo Indian Journal of Pharmacology vol37 no 6 pp 376ndash380 2005

[32] S S Reddy P Ramatholisamma R Karuna and D Saralaku-mari ldquoPreventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress inmale Wistar ratsrdquo Food and Chemical Toxicology vol 47 no 9pp 2224ndash2229 2009

[33] T DrsquoSouza S Mengi S Hassarajani and S ChattopadhayayldquoEfficacy study of the bioactive fraction (F-3) of Acorus calamusin hyperlipidemiardquo Indian Journal of Pharmacology vol 39 no4 pp 196ndash200 2007

[34] P O Bonetti D R Holmes Jr A Lerman and G W BarsnessldquoEnhanced external counterpulsation for ischemic heart dis-ease whatrsquos behind the curtainrdquo Journal of the AmericanCollegeof Cardiology vol 41 no 11 pp 1918ndash1925 2003

[35] L K Mehta R Balaraman A H Amin P A Bafna and OD Gulati ldquoEffect of fruits of Moringa oleifera on the lipidprofile of normal and hypercholesterolaemic rabbitsrdquo Journal ofEthnopharmacology vol 86 no 2-3 pp 191ndash195 2003

Submit your manuscripts athttpwwwhindawicom

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Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

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MEDIATORSINFLAMMATION

of

ISRN Pharmacology 3

27 Measurement of Body Weight Relative Liver and HeartWeight of Rats Body weights of animals of all groups weremeasured every week But relative liver and heart weight ofthe animals were measured on the 29th day after sacrificingthe animals Relative liver and heart weight were calculatedby applying the following formula [17]

Relative weight = (Organ weightBody weight

) times 100 (1)

28 Biochemical Estimations in Serum On day 29 animalswere sacrificed by carotid artery bleeding under light anesthe-sia with diethyl ether and blood samples (about 05mL fromeach animal) were collected Blood was kept for 30min forcoagulation and then serum was separated by centrifugationat 3000 rpm using centrifuge (Remi Mumbai) Total choles-terol [18] HDL-cholesterol [19] and triglycerides [20] weremeasured in serum samples using commercially biochemicalkits (Erba Diagnostics Mannheim Germany) The sampleswere analyzed by using semiautomatic autoanalyzer (Chem 5plus-V

2autoanalyzer Erba Mannheim Germany)

29 Biochemical Estimations in Liver Homogenate

291 Estimation of Reduced Glutathione (GSH) LevelsReduced glutathione levels were measured in liverhomogenate by using the procedure as reported earlier[21] The tissue sample (200mg of liver) was homogenizedin 80mL of 002M EDTA in an ice bath The homogenateswere kept in the ice bath until used Aliquots of 50mL ofthe homogenates were mixed in 150mL test tubes with40mL distilled water and 10mL of 50 trichloroaceticacid (TCA) The tubes were centrifuged for 15min at3000 rpm The supernatant (20mL) was mixed with 40mLof 04M Tris buffer (pH 89) followed by addition of01mL Ellmanrsquos reagent [55-dithiobis-(2-nitrobenzoicacid)]and the sample was shaken The absorbance was readwithin 5min of the addition of DTNB at 412 nm against areagent blank with no homogenate using double beam UV-Visible spectrophotometer (Varian Cary 5000 UV-VIS-NIRSpectrophotometer The Netherland)

292 Estimation of Malondialdehyde Levels Malondialde-hyde (MDA) an index of free radical generationlipid per-oxidation was measured in liver homogenate by using theprocedure as reported earlier [22] The tissue sample (100mgof liver) was homogenized in 90mL of KCL Briefly thereaction mixture consisted of 02mL of 81 sodium laurylsulphate 15mL of 20 acetic acid (pH 35) and 15mL of08 aqueous solution of thiobarbituric acid added to 02mLof liver homogenate The mixture was made up to 40mLwith distilled water and heated at 95∘C for 60min Aftercooling the contents under running tap water 50mL of n-butanol and pyridine (15 1 vv) and 10mL of distilled waterwere addedThe contents were centrifuged at about 4000 rpmfor 10min The organic layer was separated out and itsabsorbance was measured at 532 nm using double beam UV-Visible spectrophotometer (Varian Cary 5000 UV-VIS-NIR

SpectrophotometerThe Netherland) against a reagent blankMDA values were calculated using the extinction coefficientof MDA-thiobarbituric acid complex 156 times 105 lmol times cmand expressed as nmolmg tissue

293 Estimation of HMG-CoA Reductase Activity (HMG-CoAMevalonate Ratio) HMG-CoA reductase activity wasmeasured in liver homogenate using the procedure of Venu-gopala Rao and Ramakrishnan [23] The ratio of HMG-CoAtomevalonate was taken as an index of enzyme activity whichcatalyzes the conversion of HMG to mevalonate The lowerthe ratio the higher the enzyme activity The liver sample(100mg) was homogenized in 10mL of arsenate (1 gmL)solution Equal volumes (05mL each) of fresh liver 10tissue homogenate and diluted perchloric acid (50mLL)were mixed together This was allowed to stand for 5 minuteand centrifuged at about 2000 rpm for 10min This wasfiltered and 1mL of filtrate was mixed with 05mL of freshlyprepared hydroxyl amine (2molL) reagent of pH 55 forHMG-CoA and with 05mL of freshly prepared hydroxylamine (2molL) reagent of pH 21 for mevalonate After5 minutes 15mL of ferric chloride reagent (prepared bydissolving 52 gm of trichloroacetic acid and 10 gm of ferricchloride in 50mL of 065molL HCl) was added to each ofthe test tube for HMG-CoA and mevalonate The tubes wereshaken well Absorbance was read after 10min at 540 nmversus a similarly treated arsenate blank using double beamUV-Visible spectrophotometer (Varian Cary 5000 UV-VIS-NIR Spectrophotometer The Netherland)

210 Statistical Analysis All values were expressed as meanplusmn SEM The data were statistically analyzed using one-wayANOVA followed by Tukey-Kramer multiple comparisontest The 119875 lt 005 was considered to be statisticallysignificant

3 Results

31 Effects of Dried Pulp of Aloe succotrina Leaves on High FatDiet-Induced Hyperlipidemic Rats

311 Effect of Aloe succotrina on Body Weight High fatdiet significantly increased the body weight as compared tovehicle treated control after 2 weeks of treatment and thisincrease in body weight continued up to 4 weeks Dried pulpof Aloe succotrina leaves (100mg and 200mgkg po) andatorvastatin per se administered from the 15th day to the 28thday did not significantly decrease the body weights of high fatdiet-induced hyperlipidemic rats at the 3rd and 4th weeks oftreatment as compared to their respective high fat diet control(Table 1)

312 Effect of Aloe succotrina on Relative Liver and HeartWeight High fat diet significantly increased the relative liverweight of rats but did not significantly increase the relativeheart weight of animals as compared to vehicle treated controlafter 28 days Dried pulp of Aloe succotrina leaves (100mgand 200mgkg po) and atorvastatin (10mgkg po) per se

4 ISRN Pharmacology

Table 1 Effect of dried pulp of Aloe succotrina leaves on body weight of HFD-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Numberof animals

Body weight (g)Week 0 Week 1 Week 2 Week 3 Week 4

1 Vehicle(1wvCMC) 10mL 6 8316 plusmn 398 8766 plusmn 409 955 plusmn 377 10333 plusmn 482 10433 plusmn 478

2Vehicle

(1wvCMC)+ HFD

10mL 6 8233 plusmn 296 10216 plusmn 319a11266 plusmn 473

c12966 plusmn 590

c13600 plusmn 575

c

3 Atorvastatin +HFD 10mg 3 8300 plusmn 444 9816 plusmn 516 11816 plusmn 837 12400 plusmn 809 13333 plusmn 1186

4 Aloe succotrina+ HFD 100mg 5 7916 plusmn 392 10183 plusmn 5134 1245 plusmn 574 10666 plusmn 548 1158 plusmn 1633

5 Aloe succotrina+ HFD 200mg 5 8183 plusmn 513 10400 plusmn 717 12983 plusmn 825 13883 plusmn 698 1506 plusmn 736

In each group values are in Mean plusmn SEM data were analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 25) = 2129 119875 lt 00001 (for HFD treated control from week 0 to week 4)F (4 25) = 1636 119875 lt 01964 (comparison among various groups at week 1)F (4 25) = 4207 119875 lt 00097 (comparison among various groups at week 2)F (4 25) = 5585 119875 lt 00024 (comparison among various groups at week 3)F (4 20) = 7901 119875 lt 00005 (comparison among various groups at week 4)a119875 lt 005 and c

119875 lt 0001 as compared to HFD treated control (week 0)

Table 2 Effect of dried pulp of Aloe succotrina leaves on relative liver and heart weight of HFD-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Number of animals Relative organ weightLiver weight Heart weight

1 Vehicle (1wvCMC) 10mL 6 498 plusmn 032 063 plusmn 007

2 Vehicle (1wvCMC) + HFD 10mL 6 780 plusmn 054

070 plusmn 004

3 Atorvastatin + HFD 10mg 3 577 plusmn 031a

059 plusmn 006

4 Aloe succotrina + HFD 100mg 5 687 plusmn 032 064 plusmn 004

5 Aloe succotrina + HFD 200mg 5 581 plusmn 034a

060 plusmn 002

Relative weight = (organ weightbody weight) times 100 Values are in Mean plusmn SEM data were analyzed by one-way ANOVA followed by Tukey-Kramer multiplecomparison testF (4 20) = 8271 119875 lt 00004 (for relative liver weight)F (4 20) = 0747 119875 lt 05715 (for relative heart weight)119875 lt 0001 as compared to vehicle treated control a119875 lt 005 as compared to HFD treated control

administered from the 15th day to the 28th day significantlydecreased relative liver weight as compared to high fat dietcontrol on the 29th day (Table 2) but did not significantlyaffect relative heart weight (Table 2)

313 Effect of Aloe succotrina on Serum Lipid ParametersHigh fat diet significantly increased serum triglyceridestotal cholesterol LDL-c VLDL and atherogenic index andsignificantly decreased HDL-cholesterol levels as comparedto vehicle treated control Dried pulp of Aloe succotrinaleaves (200mgkg po) and atorvastatin (10mgkg) per sesignificantly decreased serum total cholesterol triglyceridesVLDL LDL-c and atherogenic index and increased HDL-cholesterol levels as compared to high fat diet control Lowerdose (100mgkg) of dried pulp of Aloe succotrina leavessig-nificantly decreased serum total cholesterol and LDL-c andincreased HDL-cholesterol levels but did not significantlyaffect TG VLDL and atherogenic index as compared to highfat diet control (Table 3)

314 Effect of Aloe succotrina on Liver HMGMevalonateRatio Malondialdehyde (MDA) and Reduced Glutathione(GSH) Levels High fat diet significantly increased MDA lev-els and decreased GSH levels as compared to vehicle treatedcontrol Dried pulp of Aloe succotrina leaves (200mgkg po)and atorvastatin (10mgkg) per se significantly increasedHMGmevalonate ratio (or decreased HMG-CoA reductaseactivity) decreased MDA levels and increased GSH levels ascompared to high fat diet control Lower dose (100mgkg)of dried pulp of Aloe succotrina leaves significantly decreasedMDA levels and did not significantly affect GSH and HMG-CoA reductase activity as compared to high fat diet control(Table 4)

32 Effect of Dried Pulp of Aloe succotrina Leaves on Fructose-Induced Hyperlipidemic Rats

321 Effect of Aloe succotrina on Body Weight Fructose(25 wv) dried pulp of Aloe succotrina leaves (100mg and200mgkg po) and atorvastatin (10mgkg po) per se did

ISRN Pharmacology 5

Table 3 Effect of dried pulp of Aloe succotrina leaves on serum lipid levels in HFD-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Lipid levels (mgdL)

TC TG HDL-c VLDL LDL-c AI(TGHDL)

1Vehicle

(1wvCMC)(119899 = 6)

10mL 7824 plusmn 408 1955 plusmn 504 3718 plusmn 045 391 plusmn 101 3699 plusmn 464 028 plusmn 007

2Vehicle

(1wvCMC)+ HFD (119899 = 6)

10mL 31542 plusmn 2717 10804 plusmn 1167 1738 plusmn 397 2160 plusmn 234 27640 plusmn 2638 1057 plusmn 386

3 Atorvastatin +HFD (119899 = 3) 10mg 15606 plusmn 2065c 2842 plusmn 665

b5037 plusmn 367

c568 plusmn 133

b10000 plusmn 2036

c055 plusmn 009

a

4 Aloe succotrina+ HFD (119899 = 5) 100mg 23132 plusmn 2200a 9490 plusmn 2138 3394 plusmn 330

b1898 plusmn 428 17845 plusmn 2240

b284 plusmn 063

5 Aloe succotrina+ HFD (119899 = 5) 200mg 18130 plusmn 1226c 4834 plusmn 966

a4765 plusmn 124

c967 plusmn 193

a12398 plusmn 1170

c102 plusmn 022

a

Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison test TCmdashtotal cholesterol TGmdashtriglycerides HDL-cmdashhigh density lipoprotein-cholesterol LDL-cmdashlow density lipoprotein-cholesterol VLDLmdashvery low density lipoprotein- cholesterolAImdashatherogenic indexF (4 20) = 25856 119875 lt 00001 (for total cholesterol)F (4 20) = 10308 119875 lt 00001 (for triglycerides)F (4 20) = 21007 119875 lt 00001 (for HDL-c)F (4 20) = 10297 119875 lt 00001 (for VLDL)F (4 20) = 27085 119875 lt 00001 (for LDL-c)F (4 20) = 4623 119875 lt 00083 (for AI)119875 lt 005 and

119875 lt 0001 as compared to vehicle treated control a119875 lt 005 b119875 lt 001 and c119875 lt 0001 as compared to HFD treated control

Table 4 Effect of dried pulp of Aloe succotrina leaves on liver HMGmevalonate ratio malondialdehyde (MDA) and reduced glutathione(GSH) levels of HFD-induced hyperlipidemic rats

Groupnumber Treatment (po) Dose (kgminus1) Number of animals HMGmevalonate

ratioMDA levels

(nmolmg tissue)GSH levels

(120583molmg tissue)

1 Vehicle(1wvCMC) 10mL 6 059 plusmn 023 5260 plusmn 1049 73521 plusmn 5731

2Vehicle

(1wvCMC) +HFD

10mL 6 037 plusmn 013 17974 plusmn 237729762 plusmn 2481

3 Atorvastatin + HFD 10mg 3 329 plusmn 037c

1343 plusmn 465c

66584 plusmn 2434c

4 Aloe succotrina +HFD 100mg 5 081 plusmn 013 7856 plusmn 2766

b30384 plusmn 3185

5 Aloe succotrina +HFD 200mg 5 168 plusmn 034

b5272 plusmn 1232

c61786 plusmn 2635

c

Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 20) = 14402 119875 lt 00001 (for HMGmevalonate ratio)F (4 20) = 10117 119875 lt 00001 (for MDA levels)F (4 20) = 25390 119875 lt 00001 (for reduced glutathione levels)119875 lt 001 and

119875 lt 0001 as compared to vehicle treated control b119875 lt 005 and c119875 lt 0001 as compared to HFD treated control

not significantly affect the body weight of rats as compared tovehicle treated control (Table 5)

322 Effect of Aloe succotrina on Relative Liver and HeartWeight Fructose (25 wv) significantly increased the rel-ative liver weight of animals but did not significantly increasethe relative heart weight of animals as compared to vehicletreated control after 28 days Dried pulp of Aloe succot-rina leaves (100mg and 200mgkg po) and atorvastatin(10mgkg po) per se significantly decreased relative liverweight of animals as compared to fructose treated control but

did not significantly affect relative heart weight of animals(Table 6)

323 Effect of Aloe succotrina on Serum Lipid Parame-ters Fructose (25 wv) significantly increased serum totalcholesterol triglycerides VLDL LDL-c and atherogenicindex and significantly decreased HDL-cholesterol levels ascompared to vehicle treated control Dried pulp of Aloesuccotrina leaves (200mgkg po) and atorvastatin (10mgkgpo) per se significantly decreased serum total cholesteroltriglycerides VLDL LDL-c and atherogenic index and

6 ISRN Pharmacology

Table 5 Effect of dried pulp of Aloe succotrina leaves on body weight of fructose-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Body weight (g)Week 0 Week 1 Week 2 Week 3 Week 4

1 Vehicle(1wvCMC)0 10mL 8066 plusmn 439 8383 plusmn 543 9400 plusmn 497 10233 plusmn 469 11416 plusmn 552

2Vehicle

(1wvCMC) +fructose (25wv)

10mL 8116 plusmn 735 8816 plusmn 900 9200 plusmn 1034 9516 plusmn 1042 10683 plusmn 1108

3 Atorvastatin +fructose (25wv) 10mg 7866 plusmn 354 8683 plusmn 433 9566 plusmn 475 10283 plusmn 352 11316 plusmn 309

4 Aloe succotrina +fructose (25wv) 100mg 8316 plusmn 540 9166 plusmn 719 9983 plusmn 704 9683 plusmn 656 1068 plusmn 950

5 Aloe succotrina +fructose (25wv) 200mg 8083 plusmn 447 865 plusmn 613 9616 plusmn 550 10600 plusmn 444 11916 plusmn 614

(119899 = 5) in each group Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 25) = 095 119875 lt 004516 (for fructose treated control from week 0 to week 4)F (4 25) = 019 119875 lt 09431 (comparison among various groups at week 1)F (4 25) = 018 119875 lt 09464 (comparison among various groups at week 2)F (4 25) = 049 119875 lt 07422 (comparison among various groups at week 3)F (4 25) = 049 119875 lt 07432 (comparison among various groups at week 4)

Table 6 Effect of dried pulp of Aloe succotrina leaves on relative liver and heart weight of fructose-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Relative organ weightLiver weight Heart weight

1 Vehicle (1wvCMC) 10mL 348 plusmn 015 040 plusmn 001

2 Vehicle (1wvCMC) + fructose (25wv) 10mL 578 plusmn 074

042 plusmn 002

3 Atorvastatin + fructose (25wv) 10mg 387 plusmn 036a

047 plusmn 003

4 Aloe succotrina + fructose (25wv) 100mg 392 plusmn 030a

046 plusmn 002

5 Aloe succotrina + fructose (25wv) 200mg 387 plusmn 029a

049 plusmn 003

Relative weight = (organ weightbody weight) times 100(119899 = 5) in each group Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 21) = 4742 119875 lt 0007 (for relative liver weight)F (4 21) = 1594 119875 lt 01045 (for relative heart weight)119875 lt 001 as compared to vehicle treated control a119875 lt 005 as compared to fructose treated control

increased HDL-cholesterol levels as compared to fructosetreated control on the 29th day Lower dose (100mgkg) ofthe dried pulp significantly decreased serum triglyceridesVLDL and atherogenic index but did not significantly affecttotal cholesterol LDL-c and HDL-c as compared to fructosetreated control (Table 7)

324 Effect of Aloe succotrina on Liver HMGMevalonateRatio Malondialdehyde (MDA) and Reduced Glutathione(GSH) Levels Fructose (25wv) diet significantly increasedMDA and decreased GSH levels as compared to vehi-cle treated control Dried pulp of Aloe succotrina leaves(200mgkg po) and atorvastatin (10mgkg) per se signifi-cantly increased HMGmevalonate ratio and GSH levels anddecreased MDA levels as compared to fructose treated con-trol Lower dose (100mgkg) of the dried pulp significantlydecreased MDA levels but did not significantly affect GSHand HMG-CoA reductase activity as compared to fructosetreated control (Table 8)

4 Discussion

In the present study dried pulp of Aloe succotrina leavesproduced significant antihyperlipidemic effect in high fatdiet- and fructose-induced hyperlipidemic rats Rats fed withHFD or fructose for 4 successive weeks induced significanthyperlipidemia as indicated by the significant increase inserum levels of TC TG LDL-c and VLDL and decrease inserum levels of HDL-c This is supported by earlier studies[17 24 25] High fat diet had unfavorable effect on bodyweight and relative liver weight but did not significantly affectrelative heart weightThis is supported by earlier study whereHFD increased body weight and relative liver weight withoutsignificantly affecting relative heart weight [26] D-fructose(25 wv) produced increase in relative liver weight withoutsignificantly affecting body weight and relative heart weightof animals This result is also supported by the literature [17]

Fructose has been reported to induce hypertriglyc-eridemia associated with insulin resistance hyperinsuline-mia and hypertension After the absorption in GIT fructose

ISRN Pharmacology 7

Table 7 Effect of the dried pulp of Aloe succotrina leaves on serum lipid levels in fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Lipid Levels (mgdL)

TC TG HDL-c VLDL LDL-c AI(TGHDL)

1 Vehicle(1wvCMC) 10mL 6709 plusmn 274 3947 plusmn 175 3726 plusmn 183 793 plusmn 037 2183 plusmn 454 107 plusmn 006

2

Vehicle(1wvCMC)+ fructose(25wv)

10mL 8556 plusmn 437 6710 plusmn 1269 1736 plusmn 149 1342 plusmn 254 5480 plusmn 603 393 plusmn 074

3Atorvastatin +

fructose(25wv)

10mg 6432 plusmn 409a 2259 plusmn 214c 4172 plusmn 606b 452 plusmn 043c1809 plusmn 489

b060 plusmn 010

c

4Aloe succotrina+ fructose(25wv)

100mg 7197 plusmn 612 3322 plusmn 398b 4233 plusmn 548 664 plusmn 080b3853 plusmn 694 142 plusmn 032

c

5Aloe succotrina+ fructose(25wv)

200mg 6615 plusmn 216a 2474 plusmn 244c 2680 plusmn 471b 495 plusmn 049c1887 plusmn 527

b062 plusmn 009

c

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testTCmdashtotal cholesterol TGmdashtriglycerides HDL-cmdashhigh density lipoprotein- cholesterolLDL-cmdashlow density lipoprotein- cholesterol VLDLmdashvery low density lipoprotein- cholesterol AImdashatherogenic indexF (4 21) = 4344 119875 lt 00109 (for total cholesterol) F (4 21) = 8425 119875 lt 00004 (for triglycerides) F (4 21) = 6170 119875 lt 00021 (for HDL-c) F (4 21) = 8414119875 lt 00004 (for VLDL) F (4 21) = 8118 119875 lt 00005 (for LDL-c) F (4 21) =14361 119875 lt 00001 (for AI)119875 lt 005 119875 lt 001 and

119875 lt 0001 as compared to vehicle treated control a119875 lt 005 b119875 lt 001 and c119875 lt 0001 as compared to fructose treated control

Table 8 Effect of dried pulp ofAloe succotrina leaves on liverHMGmevalonate ratioMDA and reduced glutathione (GSH) levels of fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

HMGmevalonateratio

MDA levels (nmolmgtissue)

GSH levels (120583molmgtissue)

1 Vehicle(1wvCMC) 10mL 344 plusmn 122 764 plusmn 156 52455 plusmn 3589

2Vehicle

(1wvCMC) +fructose (25wv)

10mL 198 plusmn 036 4902 plusmn 092

31720 plusmn 1940

3 Atorvastatin +fructose (25wv) 10mg 617 plusmn 093

a692 plusmn 069

c44574 plusmn 1957

a

4 Aloe succotrina +fructose (25wv) 100mg 375 plusmn 078 3166 plusmn 833

a32404 plusmn 1331

5 Aloe succotrina +fructose (25wv) 200mg 566 plusmn 067

a885 plusmn 205

c42813 plusmn 3429

a

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 21) = 4140 119875 lt 00001 (for HMGmevalonate ratio)F (4 21) = 7607 119875 lt 00007 (for MDA levels)F (4 21) = 11289 119875 lt 00001 (for reduced glutathione)119875 lt 0001 as compared to vehicle treated control

a119875 lt 005 b119875 lt 005 and c

119875 lt 0001 as compared to fructose treated control

is transported via portal circulation to the liver whereit enters hepatocytes via the glucose transporter GLUT-5independently of insulin and is rapidly metabolised Fruc-tose is metabolised into ldquoglycerol-3-phosphaterdquo and ldquoacetylCoArdquo These two intermediate metabolites are then used assubstrates for glycerides synthesis contributing to VLDL-TG production in liver The exposure of liver to suchlarge quantities of fructose leads to rapid stimulation oflipogenesis and triglyceride accumulation which in turncontributes to reduced insulin sensitivity and hepatic insulinresistanceglucose intolerance [25 27]

In both HFD and fructose-induced hyperlipidemia mod-els dried pulp of Aloe succotrina leaves (200mgkg po)significantly decreased total cholesterol triglycerides LDL-c VLDL atherogenic index and liver weight and increasedHDL-c levels Antihyperlipidemic effect of the dried pulp wascomparable to atorvastatin a standard antihyperlipidemicdrug (a HMG-CoA reductase inhibitor)

Hyperlipidemia is thought to increase cholesterol con-tent and this in turn leads to generation of reactive oxy-gen species (ROS) increase in lipid peroxidation [28] anddecrease in activity of reduced glutathione It has been

8 ISRN Pharmacology

reported that overproduction of ROS can induce cellulardamage via oxidation of critical cellular components suchas membrane lipids proteins and DNA [29] The increasedlevels of total cholesterol in blood could induce arterialendothelial dysfunction and vascular endothelial injury isthe initial factor in atherosclerosis Therefore lowering lipidand protecting vascular endothelium play significant roles inpreventing atherosclerosis [30]

Previous studies showed that high fat diet [31] or fructose[25] enhanced hepatic oxidative damage due to hepaticstress resulting from the burden of high fat diet or fructosemetabolism In the present study HFD or fructose signifi-cantly increased liver MDA levels and decreased GSH levelsindicating enhancement of oxidative stressThese findings arein agreement with earlier reports [32] Dried pulp of Aloesuccotrina leaves (200mgkg) significantly increased liverGSH levels and decreased MDA levels in both HFD andfructose-induced hyperlipidemic rats thus reduced oxidativestress

To identify the possible mechanism of the antihyper-lipidemic effect of the dried pulp more specifically theactivity of HMG-CoA reductase was determined Cholesterolhomeostasis is maintained by the two processes namelycholesterol biosynthesis in which HMG-CoA reductase cat-alyzes rate limiting process and cholesterol absorption ofboth dietary cholesterol and cholesterol cleared from the liverthrough biliary secretion [33] The HMG-CoAmevalonateratio has an inverse relationship to the activity HMG-CoAreductase The result of the present study indicated that theactivity of HMG-CoA reductase is significantly inhibited bythe dried pulp of Aloe succotrina leaves (200mgkg) in bothHFD and fructose-induced hyperlipidemic rats

Hyperlipidemia is awell-known risk factor for atheroscle-rosis which is a major contributor to the pathogenesis ofheart and vascular diseases Elevated blood concentrationof cholesterol especially in LDL-c constitutes the key riskfactor for atherosclerosis [34] Atherogenic index indicatesthe deposition of foam cells or plaque or fatty infiltrationor lipids in heart coronaries aorta liver and kidneys Thehigher the atherogenic index the higher the risk of theabove organs for oxidative damage [35]Aloe succotrina leaves(200mgkg) also markedly lowered atherogenic index inboth HFD and fructose-induced hyperlipidemic rats Thusit indicated its potential in preventing atherosclerosis

5 Conclusions

Dried pulp of Aloe succotrina leaves produced significantantihyperlipidemic activity in both HFD and fructose-induced hyperlipidemic rats possibly through normalizationof serum lipid profile HMG-CoA reductase inhibitory activ-ity and amelioration of oxidative stress in liver Moreoverit also significantly decreased atherogenic index thus itmight possess potential in preventing atherosclerosis Furtherstudies are required to isolate the active constituents involvedin antihyperlipidemic activity of Aloe succotrina Thus driedpulp ofAloe succotrina leavesmay be explored for its potentialin the prevention and treatment of clinical hyperlipidemia

Conflict of Interests

Theauthors do not have any conflict of interests regarding thecontent of this research paper

Acknowledgment

The authors are thankful to Ranbaxy Laboratories PvtLtd Gurgaon (Haryana India) for providing gift sample ofatorvastatin

References

[1] G D Kolovou K K Anagnostopoulou and D V CokkinosldquoPathophysiology of dyslipidaemia in themetabolic syndromerdquoPostgraduate Medical Journal vol 81 no 956 pp 358ndash3662005

[2] R M Krauss and Y A Kesaniemi ldquoCardiovascular disease andhyperlipidaemiardquo Current Opinion in Lipidology vol 5 no 4pp 249ndash251 1994

[3] N J Stone ldquoLipidmanagement current diet and drug treatmentoptionsrdquo The American Journal of Medicine vol 101 no 4supplement 1 pp 40Sndash49S 1996

[4] Y Lin S S Mousa N Elshourbagy and S A Mousa ldquoCurrentstatus and future directions in lipid management emphasiz-ing low-density lipoproteins high-density lipoproteins andtriglycerides as targets for therapyrdquo Vascular Health and RiskManagement vol 6 no 1 pp 73ndash85 2010

[5] M Kobayashi T Kagawa K Narumi S Itagaki T Hiranoand K Iseki ldquoBicarbonate supplementation as a preventive wayin statins-induced muscle damagerdquo Journal of Pharmacy andPharmaceutical Sciences vol 11 no 1 pp 1ndash8 2008

[6] J R Guyton and H E Bays ldquoSafety considerations with niacintherapyrdquoThe American Journal of Cardiology vol 99 no 6 ppS22ndashS31 2007

[7] W C Lakey N Greyshock and J R Guyton ldquoAdverse reactionsof Achilles tendon xanthomas in three hypercholesterolemicpatients after treatment intensification with niacin and bile acidsequestrantsrdquo Journal of Clinical Lipidology vol 7 no 2 pp 178ndash181 2013

[8] M Kiskac M Zorlu M Cakirca et al ldquoA case of rhabdomy-olysis complicated with acute renal failure after resumption offenofibrate therapy a first reportrdquo Indian Journal of Pharmacol-ogy vol 45 no 3 pp 305ndash306 2013

[9] Y-Y Yeh and L Liu ldquoCholesterol-lowering effect of garlicextracts and organosulfur compounds human and animalstudiesrdquo Journal of Nutrition vol 131 no 3 pp 989Sndash993S 2001

[10] R B Singh M A Niaz and S Ghosh ldquoHypolipidemic andantioxidant effects of commiphora mukul as an adjunct todietary therapy in patients with hypercholesterolemiardquo Cardio-vascular Drugs andTherapy vol 8 no 4 pp 659ndash664 1994

[11] W W Wong E OrsquoBrian Smith J E Stuff D L Hachey WC Heird and H J Pownell ldquoCholesterol-lowering effect ofsoy protein in normocholesterolemic and hypercholesterolemicmenrdquoThe American Journal of Clinical Nutrition vol 68 no 6pp 13855Sndash13895S 1998

[12] A M Sabzghabaee M Dianatkhah N Sarrafzadegan SAsgary and A Ghannadi ldquoClinical evaluation of Nigella sativaseeds for the treatment of hyperlipidemia a randomizedplacebo controlled clinical trialrdquo Medical Archives vol 66 no3 pp 198ndash200 2012

ISRN Pharmacology 9

[13] R Sola E Bruckert R-M Valls et al ldquoSoluble fibre (Plantagoovata husk) reduces plasma low-density lipoprotein (LDL)cholesterol triglycerides insulin oxidised LDL and systolicblood pressure in hypercholesterolaemic patients a randomisedtrialrdquo Atherosclerosis vol 211 no 2 pp 630ndash637 2010

[14] R L Van Zyl and A M Viljoen ldquoIn vitro activity of Aloeextracts against Plasmodium falciparumrdquo South African Journalof Botany vol 68 no 1 pp 106ndash110 2002

[15] D K Patel R Kumar D Laloo and S Hemalatha ldquoNaturalmedicines from plant source used for therapy of diabetesmellitus an overview of its pharmacological aspectsrdquo pp 239ndash250 2012

[16] B Lu D Xia W Huang X Wu Y Zhang and Y YaoldquoHypolipidemic effect of bamboo shoot oil (P pubescens) inSprague-Dawley ratsrdquo Journal of Food Science vol 75 no 6 ppH205ndashH211 2010

[17] N Taleb-Dida D Krouf and M Bouchenak ldquoGlobulariaalypum aqueous extract decreases hypertriglyceridemia andameliorates oxidative status of the muscle kidney and heart inrats fed a high-fructose dietrdquo Nutrition Research vol 31 no 6pp 488ndash495 2011

[18] C C Allain L S Poon and C S G Chan ldquoEnzymaticdetermination of total serum cholesterolrdquo Clinical Chemistryvol 20 no 4 pp 470ndash475 1974

[19] M Burstein H R Scholnick and RMorfin ldquoRapidmethod forthe isolation of lipoproteins fromhuman serumby precipitationwith polyanionsrdquo Journal of Lipid Research vol 11 no 6 pp583ndash595 1970

[20] MWMcGowan J D Artiss D R Strandbergh and B Zak ldquoAperoxidase-coupledmethod for the colorimetric determinationof serum triglyceridesrdquo Clinical Chemistry vol 29 no 3 pp538ndash542 1983

[21] J Sedlak and R H Lindsay ldquoEstimation of total protein-bound andnonprotein sulfhydryl groups in tissuewith Ellmanrsquosreagentrdquo Analytical Biochemistry vol 25 pp 192ndash205 1968

[22] H Ohkawa N Ohishi and K Yagi ldquoAssay for lipid peroxidesin animal tissues by thiobarbituric acid reactionrdquo AnalyticalBiochemistry vol 95 no 2 pp 351ndash358 1979

[23] A Venugopala Rao and S Ramakrishnan ldquoIndirect assessmentof hydroxymethylglutaryl CoA reductase (NADPH) activity inliver tissuerdquo Clinical Chemistry vol 21 no 10 pp 1523ndash15251975

[24] A R Borate A A Suralkar S S Birje P V Malusare and PA Bangale ldquoAntihyperlipidemic effect of protocatechuic acid infructose induced hyperlipidemia in ratsrdquo International Journalof Pharma and Bio Sciences vol 2 no 4 pp 456ndash460 2011

[25] G L Kelley G Allan and S Azhar ldquoHigh dietary fructoseinduces a hepatic stress response resulting in cholesterol andlipid dysregulationrdquo Endocrinology vol 145 no 2 pp 548ndash5552004

[26] J Fu X Zhang K Liu et al ldquoHypolipidemic activity in Sprague-Dawley rats and constituents of a novel natural vegetable oilfrom Cornus wilsoniana fruitsrdquo Journal of Food Science vol 77pp 160ndash169 2012

[27] O-J Park D Cesar D Faix K Wu C H L Shackleton andM K Hellerstein ldquoMechanisms of fructose-induced hyper-triglyceridaemia in the rat Activation of hepatic pyruvatedehydrogenase through inhibition of pyruvate dehydrogenasekinaserdquo Biochemical Journal vol 282 no 3 pp 753ndash757 1992

[28] R Yazdanparast S Bahramikia and A Ardestani ldquoNasturtiumofficinale reduces oxidative stress and enhances antioxidant

capacity in hypercholesterolaemic ratsrdquo Chemico-BiologicalInteractions vol 172 no 3 pp 176ndash184 2008

[29] P G Jain S D Patil N G Haswani M V Girase and SJ Surana ldquoHypolipidemic activity of Moringa oleifera LamMoringaceae on high fat diet induced hyperlipidemia in albinoratsrdquoBrazilian Journal of Pharmacognosy vol 20 no 6 pp 969ndash973 2010

[30] MValgimigli EMerli PMalagutti et al ldquoEndothelial dysfunc-tion in acute and chronic coronary syndromes evidence for apathogenetic role of oxidative stressrdquo Archives of Biochemistryand Biophysics vol 420 no 2 pp 255ndash261 2003

[31] N P Visavadiya and A V R L Narasimhacharya ldquoHypolipi-demic and antioxidant activities of Asparagus racemosus inhypercholesteremic ratsrdquo Indian Journal of Pharmacology vol37 no 6 pp 376ndash380 2005

[32] S S Reddy P Ramatholisamma R Karuna and D Saralaku-mari ldquoPreventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress inmale Wistar ratsrdquo Food and Chemical Toxicology vol 47 no 9pp 2224ndash2229 2009

[33] T DrsquoSouza S Mengi S Hassarajani and S ChattopadhayayldquoEfficacy study of the bioactive fraction (F-3) of Acorus calamusin hyperlipidemiardquo Indian Journal of Pharmacology vol 39 no4 pp 196ndash200 2007

[34] P O Bonetti D R Holmes Jr A Lerman and G W BarsnessldquoEnhanced external counterpulsation for ischemic heart dis-ease whatrsquos behind the curtainrdquo Journal of the AmericanCollegeof Cardiology vol 41 no 11 pp 1918ndash1925 2003

[35] L K Mehta R Balaraman A H Amin P A Bafna and OD Gulati ldquoEffect of fruits of Moringa oleifera on the lipidprofile of normal and hypercholesterolaemic rabbitsrdquo Journal ofEthnopharmacology vol 86 no 2-3 pp 191ndash195 2003

Submit your manuscripts athttpwwwhindawicom

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

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Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

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Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AnesthesiologyResearch and Practice

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Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

4 ISRN Pharmacology

Table 1 Effect of dried pulp of Aloe succotrina leaves on body weight of HFD-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Numberof animals

Body weight (g)Week 0 Week 1 Week 2 Week 3 Week 4

1 Vehicle(1wvCMC) 10mL 6 8316 plusmn 398 8766 plusmn 409 955 plusmn 377 10333 plusmn 482 10433 plusmn 478

2Vehicle

(1wvCMC)+ HFD

10mL 6 8233 plusmn 296 10216 plusmn 319a11266 plusmn 473

c12966 plusmn 590

c13600 plusmn 575

c

3 Atorvastatin +HFD 10mg 3 8300 plusmn 444 9816 plusmn 516 11816 plusmn 837 12400 plusmn 809 13333 plusmn 1186

4 Aloe succotrina+ HFD 100mg 5 7916 plusmn 392 10183 plusmn 5134 1245 plusmn 574 10666 plusmn 548 1158 plusmn 1633

5 Aloe succotrina+ HFD 200mg 5 8183 plusmn 513 10400 plusmn 717 12983 plusmn 825 13883 plusmn 698 1506 plusmn 736

In each group values are in Mean plusmn SEM data were analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 25) = 2129 119875 lt 00001 (for HFD treated control from week 0 to week 4)F (4 25) = 1636 119875 lt 01964 (comparison among various groups at week 1)F (4 25) = 4207 119875 lt 00097 (comparison among various groups at week 2)F (4 25) = 5585 119875 lt 00024 (comparison among various groups at week 3)F (4 20) = 7901 119875 lt 00005 (comparison among various groups at week 4)a119875 lt 005 and c

119875 lt 0001 as compared to HFD treated control (week 0)

Table 2 Effect of dried pulp of Aloe succotrina leaves on relative liver and heart weight of HFD-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Number of animals Relative organ weightLiver weight Heart weight

1 Vehicle (1wvCMC) 10mL 6 498 plusmn 032 063 plusmn 007

2 Vehicle (1wvCMC) + HFD 10mL 6 780 plusmn 054

070 plusmn 004

3 Atorvastatin + HFD 10mg 3 577 plusmn 031a

059 plusmn 006

4 Aloe succotrina + HFD 100mg 5 687 plusmn 032 064 plusmn 004

5 Aloe succotrina + HFD 200mg 5 581 plusmn 034a

060 plusmn 002

Relative weight = (organ weightbody weight) times 100 Values are in Mean plusmn SEM data were analyzed by one-way ANOVA followed by Tukey-Kramer multiplecomparison testF (4 20) = 8271 119875 lt 00004 (for relative liver weight)F (4 20) = 0747 119875 lt 05715 (for relative heart weight)119875 lt 0001 as compared to vehicle treated control a119875 lt 005 as compared to HFD treated control

administered from the 15th day to the 28th day significantlydecreased relative liver weight as compared to high fat dietcontrol on the 29th day (Table 2) but did not significantlyaffect relative heart weight (Table 2)

313 Effect of Aloe succotrina on Serum Lipid ParametersHigh fat diet significantly increased serum triglyceridestotal cholesterol LDL-c VLDL and atherogenic index andsignificantly decreased HDL-cholesterol levels as comparedto vehicle treated control Dried pulp of Aloe succotrinaleaves (200mgkg po) and atorvastatin (10mgkg) per sesignificantly decreased serum total cholesterol triglyceridesVLDL LDL-c and atherogenic index and increased HDL-cholesterol levels as compared to high fat diet control Lowerdose (100mgkg) of dried pulp of Aloe succotrina leavessig-nificantly decreased serum total cholesterol and LDL-c andincreased HDL-cholesterol levels but did not significantlyaffect TG VLDL and atherogenic index as compared to highfat diet control (Table 3)

314 Effect of Aloe succotrina on Liver HMGMevalonateRatio Malondialdehyde (MDA) and Reduced Glutathione(GSH) Levels High fat diet significantly increased MDA lev-els and decreased GSH levels as compared to vehicle treatedcontrol Dried pulp of Aloe succotrina leaves (200mgkg po)and atorvastatin (10mgkg) per se significantly increasedHMGmevalonate ratio (or decreased HMG-CoA reductaseactivity) decreased MDA levels and increased GSH levels ascompared to high fat diet control Lower dose (100mgkg)of dried pulp of Aloe succotrina leaves significantly decreasedMDA levels and did not significantly affect GSH and HMG-CoA reductase activity as compared to high fat diet control(Table 4)

32 Effect of Dried Pulp of Aloe succotrina Leaves on Fructose-Induced Hyperlipidemic Rats

321 Effect of Aloe succotrina on Body Weight Fructose(25 wv) dried pulp of Aloe succotrina leaves (100mg and200mgkg po) and atorvastatin (10mgkg po) per se did

ISRN Pharmacology 5

Table 3 Effect of dried pulp of Aloe succotrina leaves on serum lipid levels in HFD-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Lipid levels (mgdL)

TC TG HDL-c VLDL LDL-c AI(TGHDL)

1Vehicle

(1wvCMC)(119899 = 6)

10mL 7824 plusmn 408 1955 plusmn 504 3718 plusmn 045 391 plusmn 101 3699 plusmn 464 028 plusmn 007

2Vehicle

(1wvCMC)+ HFD (119899 = 6)

10mL 31542 plusmn 2717 10804 plusmn 1167 1738 plusmn 397 2160 plusmn 234 27640 plusmn 2638 1057 plusmn 386

3 Atorvastatin +HFD (119899 = 3) 10mg 15606 plusmn 2065c 2842 plusmn 665

b5037 plusmn 367

c568 plusmn 133

b10000 plusmn 2036

c055 plusmn 009

a

4 Aloe succotrina+ HFD (119899 = 5) 100mg 23132 plusmn 2200a 9490 plusmn 2138 3394 plusmn 330

b1898 plusmn 428 17845 plusmn 2240

b284 plusmn 063

5 Aloe succotrina+ HFD (119899 = 5) 200mg 18130 plusmn 1226c 4834 plusmn 966

a4765 plusmn 124

c967 plusmn 193

a12398 plusmn 1170

c102 plusmn 022

a

Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison test TCmdashtotal cholesterol TGmdashtriglycerides HDL-cmdashhigh density lipoprotein-cholesterol LDL-cmdashlow density lipoprotein-cholesterol VLDLmdashvery low density lipoprotein- cholesterolAImdashatherogenic indexF (4 20) = 25856 119875 lt 00001 (for total cholesterol)F (4 20) = 10308 119875 lt 00001 (for triglycerides)F (4 20) = 21007 119875 lt 00001 (for HDL-c)F (4 20) = 10297 119875 lt 00001 (for VLDL)F (4 20) = 27085 119875 lt 00001 (for LDL-c)F (4 20) = 4623 119875 lt 00083 (for AI)119875 lt 005 and

119875 lt 0001 as compared to vehicle treated control a119875 lt 005 b119875 lt 001 and c119875 lt 0001 as compared to HFD treated control

Table 4 Effect of dried pulp of Aloe succotrina leaves on liver HMGmevalonate ratio malondialdehyde (MDA) and reduced glutathione(GSH) levels of HFD-induced hyperlipidemic rats

Groupnumber Treatment (po) Dose (kgminus1) Number of animals HMGmevalonate

ratioMDA levels

(nmolmg tissue)GSH levels

(120583molmg tissue)

1 Vehicle(1wvCMC) 10mL 6 059 plusmn 023 5260 plusmn 1049 73521 plusmn 5731

2Vehicle

(1wvCMC) +HFD

10mL 6 037 plusmn 013 17974 plusmn 237729762 plusmn 2481

3 Atorvastatin + HFD 10mg 3 329 plusmn 037c

1343 plusmn 465c

66584 plusmn 2434c

4 Aloe succotrina +HFD 100mg 5 081 plusmn 013 7856 plusmn 2766

b30384 plusmn 3185

5 Aloe succotrina +HFD 200mg 5 168 plusmn 034

b5272 plusmn 1232

c61786 plusmn 2635

c

Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 20) = 14402 119875 lt 00001 (for HMGmevalonate ratio)F (4 20) = 10117 119875 lt 00001 (for MDA levels)F (4 20) = 25390 119875 lt 00001 (for reduced glutathione levels)119875 lt 001 and

119875 lt 0001 as compared to vehicle treated control b119875 lt 005 and c119875 lt 0001 as compared to HFD treated control

not significantly affect the body weight of rats as compared tovehicle treated control (Table 5)

322 Effect of Aloe succotrina on Relative Liver and HeartWeight Fructose (25 wv) significantly increased the rel-ative liver weight of animals but did not significantly increasethe relative heart weight of animals as compared to vehicletreated control after 28 days Dried pulp of Aloe succot-rina leaves (100mg and 200mgkg po) and atorvastatin(10mgkg po) per se significantly decreased relative liverweight of animals as compared to fructose treated control but

did not significantly affect relative heart weight of animals(Table 6)

323 Effect of Aloe succotrina on Serum Lipid Parame-ters Fructose (25 wv) significantly increased serum totalcholesterol triglycerides VLDL LDL-c and atherogenicindex and significantly decreased HDL-cholesterol levels ascompared to vehicle treated control Dried pulp of Aloesuccotrina leaves (200mgkg po) and atorvastatin (10mgkgpo) per se significantly decreased serum total cholesteroltriglycerides VLDL LDL-c and atherogenic index and

6 ISRN Pharmacology

Table 5 Effect of dried pulp of Aloe succotrina leaves on body weight of fructose-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Body weight (g)Week 0 Week 1 Week 2 Week 3 Week 4

1 Vehicle(1wvCMC)0 10mL 8066 plusmn 439 8383 plusmn 543 9400 plusmn 497 10233 plusmn 469 11416 plusmn 552

2Vehicle

(1wvCMC) +fructose (25wv)

10mL 8116 plusmn 735 8816 plusmn 900 9200 plusmn 1034 9516 plusmn 1042 10683 plusmn 1108

3 Atorvastatin +fructose (25wv) 10mg 7866 plusmn 354 8683 plusmn 433 9566 plusmn 475 10283 plusmn 352 11316 plusmn 309

4 Aloe succotrina +fructose (25wv) 100mg 8316 plusmn 540 9166 plusmn 719 9983 plusmn 704 9683 plusmn 656 1068 plusmn 950

5 Aloe succotrina +fructose (25wv) 200mg 8083 plusmn 447 865 plusmn 613 9616 plusmn 550 10600 plusmn 444 11916 plusmn 614

(119899 = 5) in each group Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 25) = 095 119875 lt 004516 (for fructose treated control from week 0 to week 4)F (4 25) = 019 119875 lt 09431 (comparison among various groups at week 1)F (4 25) = 018 119875 lt 09464 (comparison among various groups at week 2)F (4 25) = 049 119875 lt 07422 (comparison among various groups at week 3)F (4 25) = 049 119875 lt 07432 (comparison among various groups at week 4)

Table 6 Effect of dried pulp of Aloe succotrina leaves on relative liver and heart weight of fructose-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Relative organ weightLiver weight Heart weight

1 Vehicle (1wvCMC) 10mL 348 plusmn 015 040 plusmn 001

2 Vehicle (1wvCMC) + fructose (25wv) 10mL 578 plusmn 074

042 plusmn 002

3 Atorvastatin + fructose (25wv) 10mg 387 plusmn 036a

047 plusmn 003

4 Aloe succotrina + fructose (25wv) 100mg 392 plusmn 030a

046 plusmn 002

5 Aloe succotrina + fructose (25wv) 200mg 387 plusmn 029a

049 plusmn 003

Relative weight = (organ weightbody weight) times 100(119899 = 5) in each group Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 21) = 4742 119875 lt 0007 (for relative liver weight)F (4 21) = 1594 119875 lt 01045 (for relative heart weight)119875 lt 001 as compared to vehicle treated control a119875 lt 005 as compared to fructose treated control

increased HDL-cholesterol levels as compared to fructosetreated control on the 29th day Lower dose (100mgkg) ofthe dried pulp significantly decreased serum triglyceridesVLDL and atherogenic index but did not significantly affecttotal cholesterol LDL-c and HDL-c as compared to fructosetreated control (Table 7)

324 Effect of Aloe succotrina on Liver HMGMevalonateRatio Malondialdehyde (MDA) and Reduced Glutathione(GSH) Levels Fructose (25wv) diet significantly increasedMDA and decreased GSH levels as compared to vehi-cle treated control Dried pulp of Aloe succotrina leaves(200mgkg po) and atorvastatin (10mgkg) per se signifi-cantly increased HMGmevalonate ratio and GSH levels anddecreased MDA levels as compared to fructose treated con-trol Lower dose (100mgkg) of the dried pulp significantlydecreased MDA levels but did not significantly affect GSHand HMG-CoA reductase activity as compared to fructosetreated control (Table 8)

4 Discussion

In the present study dried pulp of Aloe succotrina leavesproduced significant antihyperlipidemic effect in high fatdiet- and fructose-induced hyperlipidemic rats Rats fed withHFD or fructose for 4 successive weeks induced significanthyperlipidemia as indicated by the significant increase inserum levels of TC TG LDL-c and VLDL and decrease inserum levels of HDL-c This is supported by earlier studies[17 24 25] High fat diet had unfavorable effect on bodyweight and relative liver weight but did not significantly affectrelative heart weightThis is supported by earlier study whereHFD increased body weight and relative liver weight withoutsignificantly affecting relative heart weight [26] D-fructose(25 wv) produced increase in relative liver weight withoutsignificantly affecting body weight and relative heart weightof animals This result is also supported by the literature [17]

Fructose has been reported to induce hypertriglyc-eridemia associated with insulin resistance hyperinsuline-mia and hypertension After the absorption in GIT fructose

ISRN Pharmacology 7

Table 7 Effect of the dried pulp of Aloe succotrina leaves on serum lipid levels in fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Lipid Levels (mgdL)

TC TG HDL-c VLDL LDL-c AI(TGHDL)

1 Vehicle(1wvCMC) 10mL 6709 plusmn 274 3947 plusmn 175 3726 plusmn 183 793 plusmn 037 2183 plusmn 454 107 plusmn 006

2

Vehicle(1wvCMC)+ fructose(25wv)

10mL 8556 plusmn 437 6710 plusmn 1269 1736 plusmn 149 1342 plusmn 254 5480 plusmn 603 393 plusmn 074

3Atorvastatin +

fructose(25wv)

10mg 6432 plusmn 409a 2259 plusmn 214c 4172 plusmn 606b 452 plusmn 043c1809 plusmn 489

b060 plusmn 010

c

4Aloe succotrina+ fructose(25wv)

100mg 7197 plusmn 612 3322 plusmn 398b 4233 plusmn 548 664 plusmn 080b3853 plusmn 694 142 plusmn 032

c

5Aloe succotrina+ fructose(25wv)

200mg 6615 plusmn 216a 2474 plusmn 244c 2680 plusmn 471b 495 plusmn 049c1887 plusmn 527

b062 plusmn 009

c

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testTCmdashtotal cholesterol TGmdashtriglycerides HDL-cmdashhigh density lipoprotein- cholesterolLDL-cmdashlow density lipoprotein- cholesterol VLDLmdashvery low density lipoprotein- cholesterol AImdashatherogenic indexF (4 21) = 4344 119875 lt 00109 (for total cholesterol) F (4 21) = 8425 119875 lt 00004 (for triglycerides) F (4 21) = 6170 119875 lt 00021 (for HDL-c) F (4 21) = 8414119875 lt 00004 (for VLDL) F (4 21) = 8118 119875 lt 00005 (for LDL-c) F (4 21) =14361 119875 lt 00001 (for AI)119875 lt 005 119875 lt 001 and

119875 lt 0001 as compared to vehicle treated control a119875 lt 005 b119875 lt 001 and c119875 lt 0001 as compared to fructose treated control

Table 8 Effect of dried pulp ofAloe succotrina leaves on liverHMGmevalonate ratioMDA and reduced glutathione (GSH) levels of fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

HMGmevalonateratio

MDA levels (nmolmgtissue)

GSH levels (120583molmgtissue)

1 Vehicle(1wvCMC) 10mL 344 plusmn 122 764 plusmn 156 52455 plusmn 3589

2Vehicle

(1wvCMC) +fructose (25wv)

10mL 198 plusmn 036 4902 plusmn 092

31720 plusmn 1940

3 Atorvastatin +fructose (25wv) 10mg 617 plusmn 093

a692 plusmn 069

c44574 plusmn 1957

a

4 Aloe succotrina +fructose (25wv) 100mg 375 plusmn 078 3166 plusmn 833

a32404 plusmn 1331

5 Aloe succotrina +fructose (25wv) 200mg 566 plusmn 067

a885 plusmn 205

c42813 plusmn 3429

a

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 21) = 4140 119875 lt 00001 (for HMGmevalonate ratio)F (4 21) = 7607 119875 lt 00007 (for MDA levels)F (4 21) = 11289 119875 lt 00001 (for reduced glutathione)119875 lt 0001 as compared to vehicle treated control

a119875 lt 005 b119875 lt 005 and c

119875 lt 0001 as compared to fructose treated control

is transported via portal circulation to the liver whereit enters hepatocytes via the glucose transporter GLUT-5independently of insulin and is rapidly metabolised Fruc-tose is metabolised into ldquoglycerol-3-phosphaterdquo and ldquoacetylCoArdquo These two intermediate metabolites are then used assubstrates for glycerides synthesis contributing to VLDL-TG production in liver The exposure of liver to suchlarge quantities of fructose leads to rapid stimulation oflipogenesis and triglyceride accumulation which in turncontributes to reduced insulin sensitivity and hepatic insulinresistanceglucose intolerance [25 27]

In both HFD and fructose-induced hyperlipidemia mod-els dried pulp of Aloe succotrina leaves (200mgkg po)significantly decreased total cholesterol triglycerides LDL-c VLDL atherogenic index and liver weight and increasedHDL-c levels Antihyperlipidemic effect of the dried pulp wascomparable to atorvastatin a standard antihyperlipidemicdrug (a HMG-CoA reductase inhibitor)

Hyperlipidemia is thought to increase cholesterol con-tent and this in turn leads to generation of reactive oxy-gen species (ROS) increase in lipid peroxidation [28] anddecrease in activity of reduced glutathione It has been

8 ISRN Pharmacology

reported that overproduction of ROS can induce cellulardamage via oxidation of critical cellular components suchas membrane lipids proteins and DNA [29] The increasedlevels of total cholesterol in blood could induce arterialendothelial dysfunction and vascular endothelial injury isthe initial factor in atherosclerosis Therefore lowering lipidand protecting vascular endothelium play significant roles inpreventing atherosclerosis [30]

Previous studies showed that high fat diet [31] or fructose[25] enhanced hepatic oxidative damage due to hepaticstress resulting from the burden of high fat diet or fructosemetabolism In the present study HFD or fructose signifi-cantly increased liver MDA levels and decreased GSH levelsindicating enhancement of oxidative stressThese findings arein agreement with earlier reports [32] Dried pulp of Aloesuccotrina leaves (200mgkg) significantly increased liverGSH levels and decreased MDA levels in both HFD andfructose-induced hyperlipidemic rats thus reduced oxidativestress

To identify the possible mechanism of the antihyper-lipidemic effect of the dried pulp more specifically theactivity of HMG-CoA reductase was determined Cholesterolhomeostasis is maintained by the two processes namelycholesterol biosynthesis in which HMG-CoA reductase cat-alyzes rate limiting process and cholesterol absorption ofboth dietary cholesterol and cholesterol cleared from the liverthrough biliary secretion [33] The HMG-CoAmevalonateratio has an inverse relationship to the activity HMG-CoAreductase The result of the present study indicated that theactivity of HMG-CoA reductase is significantly inhibited bythe dried pulp of Aloe succotrina leaves (200mgkg) in bothHFD and fructose-induced hyperlipidemic rats

Hyperlipidemia is awell-known risk factor for atheroscle-rosis which is a major contributor to the pathogenesis ofheart and vascular diseases Elevated blood concentrationof cholesterol especially in LDL-c constitutes the key riskfactor for atherosclerosis [34] Atherogenic index indicatesthe deposition of foam cells or plaque or fatty infiltrationor lipids in heart coronaries aorta liver and kidneys Thehigher the atherogenic index the higher the risk of theabove organs for oxidative damage [35]Aloe succotrina leaves(200mgkg) also markedly lowered atherogenic index inboth HFD and fructose-induced hyperlipidemic rats Thusit indicated its potential in preventing atherosclerosis

5 Conclusions

Dried pulp of Aloe succotrina leaves produced significantantihyperlipidemic activity in both HFD and fructose-induced hyperlipidemic rats possibly through normalizationof serum lipid profile HMG-CoA reductase inhibitory activ-ity and amelioration of oxidative stress in liver Moreoverit also significantly decreased atherogenic index thus itmight possess potential in preventing atherosclerosis Furtherstudies are required to isolate the active constituents involvedin antihyperlipidemic activity of Aloe succotrina Thus driedpulp ofAloe succotrina leavesmay be explored for its potentialin the prevention and treatment of clinical hyperlipidemia

Conflict of Interests

Theauthors do not have any conflict of interests regarding thecontent of this research paper

Acknowledgment

The authors are thankful to Ranbaxy Laboratories PvtLtd Gurgaon (Haryana India) for providing gift sample ofatorvastatin

References

[1] G D Kolovou K K Anagnostopoulou and D V CokkinosldquoPathophysiology of dyslipidaemia in themetabolic syndromerdquoPostgraduate Medical Journal vol 81 no 956 pp 358ndash3662005

[2] R M Krauss and Y A Kesaniemi ldquoCardiovascular disease andhyperlipidaemiardquo Current Opinion in Lipidology vol 5 no 4pp 249ndash251 1994

[3] N J Stone ldquoLipidmanagement current diet and drug treatmentoptionsrdquo The American Journal of Medicine vol 101 no 4supplement 1 pp 40Sndash49S 1996

[4] Y Lin S S Mousa N Elshourbagy and S A Mousa ldquoCurrentstatus and future directions in lipid management emphasiz-ing low-density lipoproteins high-density lipoproteins andtriglycerides as targets for therapyrdquo Vascular Health and RiskManagement vol 6 no 1 pp 73ndash85 2010

[5] M Kobayashi T Kagawa K Narumi S Itagaki T Hiranoand K Iseki ldquoBicarbonate supplementation as a preventive wayin statins-induced muscle damagerdquo Journal of Pharmacy andPharmaceutical Sciences vol 11 no 1 pp 1ndash8 2008

[6] J R Guyton and H E Bays ldquoSafety considerations with niacintherapyrdquoThe American Journal of Cardiology vol 99 no 6 ppS22ndashS31 2007

[7] W C Lakey N Greyshock and J R Guyton ldquoAdverse reactionsof Achilles tendon xanthomas in three hypercholesterolemicpatients after treatment intensification with niacin and bile acidsequestrantsrdquo Journal of Clinical Lipidology vol 7 no 2 pp 178ndash181 2013

[8] M Kiskac M Zorlu M Cakirca et al ldquoA case of rhabdomy-olysis complicated with acute renal failure after resumption offenofibrate therapy a first reportrdquo Indian Journal of Pharmacol-ogy vol 45 no 3 pp 305ndash306 2013

[9] Y-Y Yeh and L Liu ldquoCholesterol-lowering effect of garlicextracts and organosulfur compounds human and animalstudiesrdquo Journal of Nutrition vol 131 no 3 pp 989Sndash993S 2001

[10] R B Singh M A Niaz and S Ghosh ldquoHypolipidemic andantioxidant effects of commiphora mukul as an adjunct todietary therapy in patients with hypercholesterolemiardquo Cardio-vascular Drugs andTherapy vol 8 no 4 pp 659ndash664 1994

[11] W W Wong E OrsquoBrian Smith J E Stuff D L Hachey WC Heird and H J Pownell ldquoCholesterol-lowering effect ofsoy protein in normocholesterolemic and hypercholesterolemicmenrdquoThe American Journal of Clinical Nutrition vol 68 no 6pp 13855Sndash13895S 1998

[12] A M Sabzghabaee M Dianatkhah N Sarrafzadegan SAsgary and A Ghannadi ldquoClinical evaluation of Nigella sativaseeds for the treatment of hyperlipidemia a randomizedplacebo controlled clinical trialrdquo Medical Archives vol 66 no3 pp 198ndash200 2012

ISRN Pharmacology 9

[13] R Sola E Bruckert R-M Valls et al ldquoSoluble fibre (Plantagoovata husk) reduces plasma low-density lipoprotein (LDL)cholesterol triglycerides insulin oxidised LDL and systolicblood pressure in hypercholesterolaemic patients a randomisedtrialrdquo Atherosclerosis vol 211 no 2 pp 630ndash637 2010

[14] R L Van Zyl and A M Viljoen ldquoIn vitro activity of Aloeextracts against Plasmodium falciparumrdquo South African Journalof Botany vol 68 no 1 pp 106ndash110 2002

[15] D K Patel R Kumar D Laloo and S Hemalatha ldquoNaturalmedicines from plant source used for therapy of diabetesmellitus an overview of its pharmacological aspectsrdquo pp 239ndash250 2012

[16] B Lu D Xia W Huang X Wu Y Zhang and Y YaoldquoHypolipidemic effect of bamboo shoot oil (P pubescens) inSprague-Dawley ratsrdquo Journal of Food Science vol 75 no 6 ppH205ndashH211 2010

[17] N Taleb-Dida D Krouf and M Bouchenak ldquoGlobulariaalypum aqueous extract decreases hypertriglyceridemia andameliorates oxidative status of the muscle kidney and heart inrats fed a high-fructose dietrdquo Nutrition Research vol 31 no 6pp 488ndash495 2011

[18] C C Allain L S Poon and C S G Chan ldquoEnzymaticdetermination of total serum cholesterolrdquo Clinical Chemistryvol 20 no 4 pp 470ndash475 1974

[19] M Burstein H R Scholnick and RMorfin ldquoRapidmethod forthe isolation of lipoproteins fromhuman serumby precipitationwith polyanionsrdquo Journal of Lipid Research vol 11 no 6 pp583ndash595 1970

[20] MWMcGowan J D Artiss D R Strandbergh and B Zak ldquoAperoxidase-coupledmethod for the colorimetric determinationof serum triglyceridesrdquo Clinical Chemistry vol 29 no 3 pp538ndash542 1983

[21] J Sedlak and R H Lindsay ldquoEstimation of total protein-bound andnonprotein sulfhydryl groups in tissuewith Ellmanrsquosreagentrdquo Analytical Biochemistry vol 25 pp 192ndash205 1968

[22] H Ohkawa N Ohishi and K Yagi ldquoAssay for lipid peroxidesin animal tissues by thiobarbituric acid reactionrdquo AnalyticalBiochemistry vol 95 no 2 pp 351ndash358 1979

[23] A Venugopala Rao and S Ramakrishnan ldquoIndirect assessmentof hydroxymethylglutaryl CoA reductase (NADPH) activity inliver tissuerdquo Clinical Chemistry vol 21 no 10 pp 1523ndash15251975

[24] A R Borate A A Suralkar S S Birje P V Malusare and PA Bangale ldquoAntihyperlipidemic effect of protocatechuic acid infructose induced hyperlipidemia in ratsrdquo International Journalof Pharma and Bio Sciences vol 2 no 4 pp 456ndash460 2011

[25] G L Kelley G Allan and S Azhar ldquoHigh dietary fructoseinduces a hepatic stress response resulting in cholesterol andlipid dysregulationrdquo Endocrinology vol 145 no 2 pp 548ndash5552004

[26] J Fu X Zhang K Liu et al ldquoHypolipidemic activity in Sprague-Dawley rats and constituents of a novel natural vegetable oilfrom Cornus wilsoniana fruitsrdquo Journal of Food Science vol 77pp 160ndash169 2012

[27] O-J Park D Cesar D Faix K Wu C H L Shackleton andM K Hellerstein ldquoMechanisms of fructose-induced hyper-triglyceridaemia in the rat Activation of hepatic pyruvatedehydrogenase through inhibition of pyruvate dehydrogenasekinaserdquo Biochemical Journal vol 282 no 3 pp 753ndash757 1992

[28] R Yazdanparast S Bahramikia and A Ardestani ldquoNasturtiumofficinale reduces oxidative stress and enhances antioxidant

capacity in hypercholesterolaemic ratsrdquo Chemico-BiologicalInteractions vol 172 no 3 pp 176ndash184 2008

[29] P G Jain S D Patil N G Haswani M V Girase and SJ Surana ldquoHypolipidemic activity of Moringa oleifera LamMoringaceae on high fat diet induced hyperlipidemia in albinoratsrdquoBrazilian Journal of Pharmacognosy vol 20 no 6 pp 969ndash973 2010

[30] MValgimigli EMerli PMalagutti et al ldquoEndothelial dysfunc-tion in acute and chronic coronary syndromes evidence for apathogenetic role of oxidative stressrdquo Archives of Biochemistryand Biophysics vol 420 no 2 pp 255ndash261 2003

[31] N P Visavadiya and A V R L Narasimhacharya ldquoHypolipi-demic and antioxidant activities of Asparagus racemosus inhypercholesteremic ratsrdquo Indian Journal of Pharmacology vol37 no 6 pp 376ndash380 2005

[32] S S Reddy P Ramatholisamma R Karuna and D Saralaku-mari ldquoPreventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress inmale Wistar ratsrdquo Food and Chemical Toxicology vol 47 no 9pp 2224ndash2229 2009

[33] T DrsquoSouza S Mengi S Hassarajani and S ChattopadhayayldquoEfficacy study of the bioactive fraction (F-3) of Acorus calamusin hyperlipidemiardquo Indian Journal of Pharmacology vol 39 no4 pp 196ndash200 2007

[34] P O Bonetti D R Holmes Jr A Lerman and G W BarsnessldquoEnhanced external counterpulsation for ischemic heart dis-ease whatrsquos behind the curtainrdquo Journal of the AmericanCollegeof Cardiology vol 41 no 11 pp 1918ndash1925 2003

[35] L K Mehta R Balaraman A H Amin P A Bafna and OD Gulati ldquoEffect of fruits of Moringa oleifera on the lipidprofile of normal and hypercholesterolaemic rabbitsrdquo Journal ofEthnopharmacology vol 86 no 2-3 pp 191ndash195 2003

Submit your manuscripts athttpwwwhindawicom

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Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

ISRN Pharmacology 5

Table 3 Effect of dried pulp of Aloe succotrina leaves on serum lipid levels in HFD-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Lipid levels (mgdL)

TC TG HDL-c VLDL LDL-c AI(TGHDL)

1Vehicle

(1wvCMC)(119899 = 6)

10mL 7824 plusmn 408 1955 plusmn 504 3718 plusmn 045 391 plusmn 101 3699 plusmn 464 028 plusmn 007

2Vehicle

(1wvCMC)+ HFD (119899 = 6)

10mL 31542 plusmn 2717 10804 plusmn 1167 1738 plusmn 397 2160 plusmn 234 27640 plusmn 2638 1057 plusmn 386

3 Atorvastatin +HFD (119899 = 3) 10mg 15606 plusmn 2065c 2842 plusmn 665

b5037 plusmn 367

c568 plusmn 133

b10000 plusmn 2036

c055 plusmn 009

a

4 Aloe succotrina+ HFD (119899 = 5) 100mg 23132 plusmn 2200a 9490 plusmn 2138 3394 plusmn 330

b1898 plusmn 428 17845 plusmn 2240

b284 plusmn 063

5 Aloe succotrina+ HFD (119899 = 5) 200mg 18130 plusmn 1226c 4834 plusmn 966

a4765 plusmn 124

c967 plusmn 193

a12398 plusmn 1170

c102 plusmn 022

a

Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison test TCmdashtotal cholesterol TGmdashtriglycerides HDL-cmdashhigh density lipoprotein-cholesterol LDL-cmdashlow density lipoprotein-cholesterol VLDLmdashvery low density lipoprotein- cholesterolAImdashatherogenic indexF (4 20) = 25856 119875 lt 00001 (for total cholesterol)F (4 20) = 10308 119875 lt 00001 (for triglycerides)F (4 20) = 21007 119875 lt 00001 (for HDL-c)F (4 20) = 10297 119875 lt 00001 (for VLDL)F (4 20) = 27085 119875 lt 00001 (for LDL-c)F (4 20) = 4623 119875 lt 00083 (for AI)119875 lt 005 and

119875 lt 0001 as compared to vehicle treated control a119875 lt 005 b119875 lt 001 and c119875 lt 0001 as compared to HFD treated control

Table 4 Effect of dried pulp of Aloe succotrina leaves on liver HMGmevalonate ratio malondialdehyde (MDA) and reduced glutathione(GSH) levels of HFD-induced hyperlipidemic rats

Groupnumber Treatment (po) Dose (kgminus1) Number of animals HMGmevalonate

ratioMDA levels

(nmolmg tissue)GSH levels

(120583molmg tissue)

1 Vehicle(1wvCMC) 10mL 6 059 plusmn 023 5260 plusmn 1049 73521 plusmn 5731

2Vehicle

(1wvCMC) +HFD

10mL 6 037 plusmn 013 17974 plusmn 237729762 plusmn 2481

3 Atorvastatin + HFD 10mg 3 329 plusmn 037c

1343 plusmn 465c

66584 plusmn 2434c

4 Aloe succotrina +HFD 100mg 5 081 plusmn 013 7856 plusmn 2766

b30384 plusmn 3185

5 Aloe succotrina +HFD 200mg 5 168 plusmn 034

b5272 plusmn 1232

c61786 plusmn 2635

c

Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 20) = 14402 119875 lt 00001 (for HMGmevalonate ratio)F (4 20) = 10117 119875 lt 00001 (for MDA levels)F (4 20) = 25390 119875 lt 00001 (for reduced glutathione levels)119875 lt 001 and

119875 lt 0001 as compared to vehicle treated control b119875 lt 005 and c119875 lt 0001 as compared to HFD treated control

not significantly affect the body weight of rats as compared tovehicle treated control (Table 5)

322 Effect of Aloe succotrina on Relative Liver and HeartWeight Fructose (25 wv) significantly increased the rel-ative liver weight of animals but did not significantly increasethe relative heart weight of animals as compared to vehicletreated control after 28 days Dried pulp of Aloe succot-rina leaves (100mg and 200mgkg po) and atorvastatin(10mgkg po) per se significantly decreased relative liverweight of animals as compared to fructose treated control but

did not significantly affect relative heart weight of animals(Table 6)

323 Effect of Aloe succotrina on Serum Lipid Parame-ters Fructose (25 wv) significantly increased serum totalcholesterol triglycerides VLDL LDL-c and atherogenicindex and significantly decreased HDL-cholesterol levels ascompared to vehicle treated control Dried pulp of Aloesuccotrina leaves (200mgkg po) and atorvastatin (10mgkgpo) per se significantly decreased serum total cholesteroltriglycerides VLDL LDL-c and atherogenic index and

6 ISRN Pharmacology

Table 5 Effect of dried pulp of Aloe succotrina leaves on body weight of fructose-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Body weight (g)Week 0 Week 1 Week 2 Week 3 Week 4

1 Vehicle(1wvCMC)0 10mL 8066 plusmn 439 8383 plusmn 543 9400 plusmn 497 10233 plusmn 469 11416 plusmn 552

2Vehicle

(1wvCMC) +fructose (25wv)

10mL 8116 plusmn 735 8816 plusmn 900 9200 plusmn 1034 9516 plusmn 1042 10683 plusmn 1108

3 Atorvastatin +fructose (25wv) 10mg 7866 plusmn 354 8683 plusmn 433 9566 plusmn 475 10283 plusmn 352 11316 plusmn 309

4 Aloe succotrina +fructose (25wv) 100mg 8316 plusmn 540 9166 plusmn 719 9983 plusmn 704 9683 plusmn 656 1068 plusmn 950

5 Aloe succotrina +fructose (25wv) 200mg 8083 plusmn 447 865 plusmn 613 9616 plusmn 550 10600 plusmn 444 11916 plusmn 614

(119899 = 5) in each group Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 25) = 095 119875 lt 004516 (for fructose treated control from week 0 to week 4)F (4 25) = 019 119875 lt 09431 (comparison among various groups at week 1)F (4 25) = 018 119875 lt 09464 (comparison among various groups at week 2)F (4 25) = 049 119875 lt 07422 (comparison among various groups at week 3)F (4 25) = 049 119875 lt 07432 (comparison among various groups at week 4)

Table 6 Effect of dried pulp of Aloe succotrina leaves on relative liver and heart weight of fructose-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Relative organ weightLiver weight Heart weight

1 Vehicle (1wvCMC) 10mL 348 plusmn 015 040 plusmn 001

2 Vehicle (1wvCMC) + fructose (25wv) 10mL 578 plusmn 074

042 plusmn 002

3 Atorvastatin + fructose (25wv) 10mg 387 plusmn 036a

047 plusmn 003

4 Aloe succotrina + fructose (25wv) 100mg 392 plusmn 030a

046 plusmn 002

5 Aloe succotrina + fructose (25wv) 200mg 387 plusmn 029a

049 plusmn 003

Relative weight = (organ weightbody weight) times 100(119899 = 5) in each group Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 21) = 4742 119875 lt 0007 (for relative liver weight)F (4 21) = 1594 119875 lt 01045 (for relative heart weight)119875 lt 001 as compared to vehicle treated control a119875 lt 005 as compared to fructose treated control

increased HDL-cholesterol levels as compared to fructosetreated control on the 29th day Lower dose (100mgkg) ofthe dried pulp significantly decreased serum triglyceridesVLDL and atherogenic index but did not significantly affecttotal cholesterol LDL-c and HDL-c as compared to fructosetreated control (Table 7)

324 Effect of Aloe succotrina on Liver HMGMevalonateRatio Malondialdehyde (MDA) and Reduced Glutathione(GSH) Levels Fructose (25wv) diet significantly increasedMDA and decreased GSH levels as compared to vehi-cle treated control Dried pulp of Aloe succotrina leaves(200mgkg po) and atorvastatin (10mgkg) per se signifi-cantly increased HMGmevalonate ratio and GSH levels anddecreased MDA levels as compared to fructose treated con-trol Lower dose (100mgkg) of the dried pulp significantlydecreased MDA levels but did not significantly affect GSHand HMG-CoA reductase activity as compared to fructosetreated control (Table 8)

4 Discussion

In the present study dried pulp of Aloe succotrina leavesproduced significant antihyperlipidemic effect in high fatdiet- and fructose-induced hyperlipidemic rats Rats fed withHFD or fructose for 4 successive weeks induced significanthyperlipidemia as indicated by the significant increase inserum levels of TC TG LDL-c and VLDL and decrease inserum levels of HDL-c This is supported by earlier studies[17 24 25] High fat diet had unfavorable effect on bodyweight and relative liver weight but did not significantly affectrelative heart weightThis is supported by earlier study whereHFD increased body weight and relative liver weight withoutsignificantly affecting relative heart weight [26] D-fructose(25 wv) produced increase in relative liver weight withoutsignificantly affecting body weight and relative heart weightof animals This result is also supported by the literature [17]

Fructose has been reported to induce hypertriglyc-eridemia associated with insulin resistance hyperinsuline-mia and hypertension After the absorption in GIT fructose

ISRN Pharmacology 7

Table 7 Effect of the dried pulp of Aloe succotrina leaves on serum lipid levels in fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Lipid Levels (mgdL)

TC TG HDL-c VLDL LDL-c AI(TGHDL)

1 Vehicle(1wvCMC) 10mL 6709 plusmn 274 3947 plusmn 175 3726 plusmn 183 793 plusmn 037 2183 plusmn 454 107 plusmn 006

2

Vehicle(1wvCMC)+ fructose(25wv)

10mL 8556 plusmn 437 6710 plusmn 1269 1736 plusmn 149 1342 plusmn 254 5480 plusmn 603 393 plusmn 074

3Atorvastatin +

fructose(25wv)

10mg 6432 plusmn 409a 2259 plusmn 214c 4172 plusmn 606b 452 plusmn 043c1809 plusmn 489

b060 plusmn 010

c

4Aloe succotrina+ fructose(25wv)

100mg 7197 plusmn 612 3322 plusmn 398b 4233 plusmn 548 664 plusmn 080b3853 plusmn 694 142 plusmn 032

c

5Aloe succotrina+ fructose(25wv)

200mg 6615 plusmn 216a 2474 plusmn 244c 2680 plusmn 471b 495 plusmn 049c1887 plusmn 527

b062 plusmn 009

c

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testTCmdashtotal cholesterol TGmdashtriglycerides HDL-cmdashhigh density lipoprotein- cholesterolLDL-cmdashlow density lipoprotein- cholesterol VLDLmdashvery low density lipoprotein- cholesterol AImdashatherogenic indexF (4 21) = 4344 119875 lt 00109 (for total cholesterol) F (4 21) = 8425 119875 lt 00004 (for triglycerides) F (4 21) = 6170 119875 lt 00021 (for HDL-c) F (4 21) = 8414119875 lt 00004 (for VLDL) F (4 21) = 8118 119875 lt 00005 (for LDL-c) F (4 21) =14361 119875 lt 00001 (for AI)119875 lt 005 119875 lt 001 and

119875 lt 0001 as compared to vehicle treated control a119875 lt 005 b119875 lt 001 and c119875 lt 0001 as compared to fructose treated control

Table 8 Effect of dried pulp ofAloe succotrina leaves on liverHMGmevalonate ratioMDA and reduced glutathione (GSH) levels of fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

HMGmevalonateratio

MDA levels (nmolmgtissue)

GSH levels (120583molmgtissue)

1 Vehicle(1wvCMC) 10mL 344 plusmn 122 764 plusmn 156 52455 plusmn 3589

2Vehicle

(1wvCMC) +fructose (25wv)

10mL 198 plusmn 036 4902 plusmn 092

31720 plusmn 1940

3 Atorvastatin +fructose (25wv) 10mg 617 plusmn 093

a692 plusmn 069

c44574 plusmn 1957

a

4 Aloe succotrina +fructose (25wv) 100mg 375 plusmn 078 3166 plusmn 833

a32404 plusmn 1331

5 Aloe succotrina +fructose (25wv) 200mg 566 plusmn 067

a885 plusmn 205

c42813 plusmn 3429

a

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 21) = 4140 119875 lt 00001 (for HMGmevalonate ratio)F (4 21) = 7607 119875 lt 00007 (for MDA levels)F (4 21) = 11289 119875 lt 00001 (for reduced glutathione)119875 lt 0001 as compared to vehicle treated control

a119875 lt 005 b119875 lt 005 and c

119875 lt 0001 as compared to fructose treated control

is transported via portal circulation to the liver whereit enters hepatocytes via the glucose transporter GLUT-5independently of insulin and is rapidly metabolised Fruc-tose is metabolised into ldquoglycerol-3-phosphaterdquo and ldquoacetylCoArdquo These two intermediate metabolites are then used assubstrates for glycerides synthesis contributing to VLDL-TG production in liver The exposure of liver to suchlarge quantities of fructose leads to rapid stimulation oflipogenesis and triglyceride accumulation which in turncontributes to reduced insulin sensitivity and hepatic insulinresistanceglucose intolerance [25 27]

In both HFD and fructose-induced hyperlipidemia mod-els dried pulp of Aloe succotrina leaves (200mgkg po)significantly decreased total cholesterol triglycerides LDL-c VLDL atherogenic index and liver weight and increasedHDL-c levels Antihyperlipidemic effect of the dried pulp wascomparable to atorvastatin a standard antihyperlipidemicdrug (a HMG-CoA reductase inhibitor)

Hyperlipidemia is thought to increase cholesterol con-tent and this in turn leads to generation of reactive oxy-gen species (ROS) increase in lipid peroxidation [28] anddecrease in activity of reduced glutathione It has been

8 ISRN Pharmacology

reported that overproduction of ROS can induce cellulardamage via oxidation of critical cellular components suchas membrane lipids proteins and DNA [29] The increasedlevels of total cholesterol in blood could induce arterialendothelial dysfunction and vascular endothelial injury isthe initial factor in atherosclerosis Therefore lowering lipidand protecting vascular endothelium play significant roles inpreventing atherosclerosis [30]

Previous studies showed that high fat diet [31] or fructose[25] enhanced hepatic oxidative damage due to hepaticstress resulting from the burden of high fat diet or fructosemetabolism In the present study HFD or fructose signifi-cantly increased liver MDA levels and decreased GSH levelsindicating enhancement of oxidative stressThese findings arein agreement with earlier reports [32] Dried pulp of Aloesuccotrina leaves (200mgkg) significantly increased liverGSH levels and decreased MDA levels in both HFD andfructose-induced hyperlipidemic rats thus reduced oxidativestress

To identify the possible mechanism of the antihyper-lipidemic effect of the dried pulp more specifically theactivity of HMG-CoA reductase was determined Cholesterolhomeostasis is maintained by the two processes namelycholesterol biosynthesis in which HMG-CoA reductase cat-alyzes rate limiting process and cholesterol absorption ofboth dietary cholesterol and cholesterol cleared from the liverthrough biliary secretion [33] The HMG-CoAmevalonateratio has an inverse relationship to the activity HMG-CoAreductase The result of the present study indicated that theactivity of HMG-CoA reductase is significantly inhibited bythe dried pulp of Aloe succotrina leaves (200mgkg) in bothHFD and fructose-induced hyperlipidemic rats

Hyperlipidemia is awell-known risk factor for atheroscle-rosis which is a major contributor to the pathogenesis ofheart and vascular diseases Elevated blood concentrationof cholesterol especially in LDL-c constitutes the key riskfactor for atherosclerosis [34] Atherogenic index indicatesthe deposition of foam cells or plaque or fatty infiltrationor lipids in heart coronaries aorta liver and kidneys Thehigher the atherogenic index the higher the risk of theabove organs for oxidative damage [35]Aloe succotrina leaves(200mgkg) also markedly lowered atherogenic index inboth HFD and fructose-induced hyperlipidemic rats Thusit indicated its potential in preventing atherosclerosis

5 Conclusions

Dried pulp of Aloe succotrina leaves produced significantantihyperlipidemic activity in both HFD and fructose-induced hyperlipidemic rats possibly through normalizationof serum lipid profile HMG-CoA reductase inhibitory activ-ity and amelioration of oxidative stress in liver Moreoverit also significantly decreased atherogenic index thus itmight possess potential in preventing atherosclerosis Furtherstudies are required to isolate the active constituents involvedin antihyperlipidemic activity of Aloe succotrina Thus driedpulp ofAloe succotrina leavesmay be explored for its potentialin the prevention and treatment of clinical hyperlipidemia

Conflict of Interests

Theauthors do not have any conflict of interests regarding thecontent of this research paper

Acknowledgment

The authors are thankful to Ranbaxy Laboratories PvtLtd Gurgaon (Haryana India) for providing gift sample ofatorvastatin

References

[1] G D Kolovou K K Anagnostopoulou and D V CokkinosldquoPathophysiology of dyslipidaemia in themetabolic syndromerdquoPostgraduate Medical Journal vol 81 no 956 pp 358ndash3662005

[2] R M Krauss and Y A Kesaniemi ldquoCardiovascular disease andhyperlipidaemiardquo Current Opinion in Lipidology vol 5 no 4pp 249ndash251 1994

[3] N J Stone ldquoLipidmanagement current diet and drug treatmentoptionsrdquo The American Journal of Medicine vol 101 no 4supplement 1 pp 40Sndash49S 1996

[4] Y Lin S S Mousa N Elshourbagy and S A Mousa ldquoCurrentstatus and future directions in lipid management emphasiz-ing low-density lipoproteins high-density lipoproteins andtriglycerides as targets for therapyrdquo Vascular Health and RiskManagement vol 6 no 1 pp 73ndash85 2010

[5] M Kobayashi T Kagawa K Narumi S Itagaki T Hiranoand K Iseki ldquoBicarbonate supplementation as a preventive wayin statins-induced muscle damagerdquo Journal of Pharmacy andPharmaceutical Sciences vol 11 no 1 pp 1ndash8 2008

[6] J R Guyton and H E Bays ldquoSafety considerations with niacintherapyrdquoThe American Journal of Cardiology vol 99 no 6 ppS22ndashS31 2007

[7] W C Lakey N Greyshock and J R Guyton ldquoAdverse reactionsof Achilles tendon xanthomas in three hypercholesterolemicpatients after treatment intensification with niacin and bile acidsequestrantsrdquo Journal of Clinical Lipidology vol 7 no 2 pp 178ndash181 2013

[8] M Kiskac M Zorlu M Cakirca et al ldquoA case of rhabdomy-olysis complicated with acute renal failure after resumption offenofibrate therapy a first reportrdquo Indian Journal of Pharmacol-ogy vol 45 no 3 pp 305ndash306 2013

[9] Y-Y Yeh and L Liu ldquoCholesterol-lowering effect of garlicextracts and organosulfur compounds human and animalstudiesrdquo Journal of Nutrition vol 131 no 3 pp 989Sndash993S 2001

[10] R B Singh M A Niaz and S Ghosh ldquoHypolipidemic andantioxidant effects of commiphora mukul as an adjunct todietary therapy in patients with hypercholesterolemiardquo Cardio-vascular Drugs andTherapy vol 8 no 4 pp 659ndash664 1994

[11] W W Wong E OrsquoBrian Smith J E Stuff D L Hachey WC Heird and H J Pownell ldquoCholesterol-lowering effect ofsoy protein in normocholesterolemic and hypercholesterolemicmenrdquoThe American Journal of Clinical Nutrition vol 68 no 6pp 13855Sndash13895S 1998

[12] A M Sabzghabaee M Dianatkhah N Sarrafzadegan SAsgary and A Ghannadi ldquoClinical evaluation of Nigella sativaseeds for the treatment of hyperlipidemia a randomizedplacebo controlled clinical trialrdquo Medical Archives vol 66 no3 pp 198ndash200 2012

ISRN Pharmacology 9

[13] R Sola E Bruckert R-M Valls et al ldquoSoluble fibre (Plantagoovata husk) reduces plasma low-density lipoprotein (LDL)cholesterol triglycerides insulin oxidised LDL and systolicblood pressure in hypercholesterolaemic patients a randomisedtrialrdquo Atherosclerosis vol 211 no 2 pp 630ndash637 2010

[14] R L Van Zyl and A M Viljoen ldquoIn vitro activity of Aloeextracts against Plasmodium falciparumrdquo South African Journalof Botany vol 68 no 1 pp 106ndash110 2002

[15] D K Patel R Kumar D Laloo and S Hemalatha ldquoNaturalmedicines from plant source used for therapy of diabetesmellitus an overview of its pharmacological aspectsrdquo pp 239ndash250 2012

[16] B Lu D Xia W Huang X Wu Y Zhang and Y YaoldquoHypolipidemic effect of bamboo shoot oil (P pubescens) inSprague-Dawley ratsrdquo Journal of Food Science vol 75 no 6 ppH205ndashH211 2010

[17] N Taleb-Dida D Krouf and M Bouchenak ldquoGlobulariaalypum aqueous extract decreases hypertriglyceridemia andameliorates oxidative status of the muscle kidney and heart inrats fed a high-fructose dietrdquo Nutrition Research vol 31 no 6pp 488ndash495 2011

[18] C C Allain L S Poon and C S G Chan ldquoEnzymaticdetermination of total serum cholesterolrdquo Clinical Chemistryvol 20 no 4 pp 470ndash475 1974

[19] M Burstein H R Scholnick and RMorfin ldquoRapidmethod forthe isolation of lipoproteins fromhuman serumby precipitationwith polyanionsrdquo Journal of Lipid Research vol 11 no 6 pp583ndash595 1970

[20] MWMcGowan J D Artiss D R Strandbergh and B Zak ldquoAperoxidase-coupledmethod for the colorimetric determinationof serum triglyceridesrdquo Clinical Chemistry vol 29 no 3 pp538ndash542 1983

[21] J Sedlak and R H Lindsay ldquoEstimation of total protein-bound andnonprotein sulfhydryl groups in tissuewith Ellmanrsquosreagentrdquo Analytical Biochemistry vol 25 pp 192ndash205 1968

[22] H Ohkawa N Ohishi and K Yagi ldquoAssay for lipid peroxidesin animal tissues by thiobarbituric acid reactionrdquo AnalyticalBiochemistry vol 95 no 2 pp 351ndash358 1979

[23] A Venugopala Rao and S Ramakrishnan ldquoIndirect assessmentof hydroxymethylglutaryl CoA reductase (NADPH) activity inliver tissuerdquo Clinical Chemistry vol 21 no 10 pp 1523ndash15251975

[24] A R Borate A A Suralkar S S Birje P V Malusare and PA Bangale ldquoAntihyperlipidemic effect of protocatechuic acid infructose induced hyperlipidemia in ratsrdquo International Journalof Pharma and Bio Sciences vol 2 no 4 pp 456ndash460 2011

[25] G L Kelley G Allan and S Azhar ldquoHigh dietary fructoseinduces a hepatic stress response resulting in cholesterol andlipid dysregulationrdquo Endocrinology vol 145 no 2 pp 548ndash5552004

[26] J Fu X Zhang K Liu et al ldquoHypolipidemic activity in Sprague-Dawley rats and constituents of a novel natural vegetable oilfrom Cornus wilsoniana fruitsrdquo Journal of Food Science vol 77pp 160ndash169 2012

[27] O-J Park D Cesar D Faix K Wu C H L Shackleton andM K Hellerstein ldquoMechanisms of fructose-induced hyper-triglyceridaemia in the rat Activation of hepatic pyruvatedehydrogenase through inhibition of pyruvate dehydrogenasekinaserdquo Biochemical Journal vol 282 no 3 pp 753ndash757 1992

[28] R Yazdanparast S Bahramikia and A Ardestani ldquoNasturtiumofficinale reduces oxidative stress and enhances antioxidant

capacity in hypercholesterolaemic ratsrdquo Chemico-BiologicalInteractions vol 172 no 3 pp 176ndash184 2008

[29] P G Jain S D Patil N G Haswani M V Girase and SJ Surana ldquoHypolipidemic activity of Moringa oleifera LamMoringaceae on high fat diet induced hyperlipidemia in albinoratsrdquoBrazilian Journal of Pharmacognosy vol 20 no 6 pp 969ndash973 2010

[30] MValgimigli EMerli PMalagutti et al ldquoEndothelial dysfunc-tion in acute and chronic coronary syndromes evidence for apathogenetic role of oxidative stressrdquo Archives of Biochemistryand Biophysics vol 420 no 2 pp 255ndash261 2003

[31] N P Visavadiya and A V R L Narasimhacharya ldquoHypolipi-demic and antioxidant activities of Asparagus racemosus inhypercholesteremic ratsrdquo Indian Journal of Pharmacology vol37 no 6 pp 376ndash380 2005

[32] S S Reddy P Ramatholisamma R Karuna and D Saralaku-mari ldquoPreventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress inmale Wistar ratsrdquo Food and Chemical Toxicology vol 47 no 9pp 2224ndash2229 2009

[33] T DrsquoSouza S Mengi S Hassarajani and S ChattopadhayayldquoEfficacy study of the bioactive fraction (F-3) of Acorus calamusin hyperlipidemiardquo Indian Journal of Pharmacology vol 39 no4 pp 196ndash200 2007

[34] P O Bonetti D R Holmes Jr A Lerman and G W BarsnessldquoEnhanced external counterpulsation for ischemic heart dis-ease whatrsquos behind the curtainrdquo Journal of the AmericanCollegeof Cardiology vol 41 no 11 pp 1918ndash1925 2003

[35] L K Mehta R Balaraman A H Amin P A Bafna and OD Gulati ldquoEffect of fruits of Moringa oleifera on the lipidprofile of normal and hypercholesterolaemic rabbitsrdquo Journal ofEthnopharmacology vol 86 no 2-3 pp 191ndash195 2003

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of AddictionHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AnesthesiologyResearch and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

6 ISRN Pharmacology

Table 5 Effect of dried pulp of Aloe succotrina leaves on body weight of fructose-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Body weight (g)Week 0 Week 1 Week 2 Week 3 Week 4

1 Vehicle(1wvCMC)0 10mL 8066 plusmn 439 8383 plusmn 543 9400 plusmn 497 10233 plusmn 469 11416 plusmn 552

2Vehicle

(1wvCMC) +fructose (25wv)

10mL 8116 plusmn 735 8816 plusmn 900 9200 plusmn 1034 9516 plusmn 1042 10683 plusmn 1108

3 Atorvastatin +fructose (25wv) 10mg 7866 plusmn 354 8683 plusmn 433 9566 plusmn 475 10283 plusmn 352 11316 plusmn 309

4 Aloe succotrina +fructose (25wv) 100mg 8316 plusmn 540 9166 plusmn 719 9983 plusmn 704 9683 plusmn 656 1068 plusmn 950

5 Aloe succotrina +fructose (25wv) 200mg 8083 plusmn 447 865 plusmn 613 9616 plusmn 550 10600 plusmn 444 11916 plusmn 614

(119899 = 5) in each group Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 25) = 095 119875 lt 004516 (for fructose treated control from week 0 to week 4)F (4 25) = 019 119875 lt 09431 (comparison among various groups at week 1)F (4 25) = 018 119875 lt 09464 (comparison among various groups at week 2)F (4 25) = 049 119875 lt 07422 (comparison among various groups at week 3)F (4 25) = 049 119875 lt 07432 (comparison among various groups at week 4)

Table 6 Effect of dried pulp of Aloe succotrina leaves on relative liver and heart weight of fructose-induced hyperlipidemic rats

Group number Treatment (po) Dose (kgminus1) Relative organ weightLiver weight Heart weight

1 Vehicle (1wvCMC) 10mL 348 plusmn 015 040 plusmn 001

2 Vehicle (1wvCMC) + fructose (25wv) 10mL 578 plusmn 074

042 plusmn 002

3 Atorvastatin + fructose (25wv) 10mg 387 plusmn 036a

047 plusmn 003

4 Aloe succotrina + fructose (25wv) 100mg 392 plusmn 030a

046 plusmn 002

5 Aloe succotrina + fructose (25wv) 200mg 387 plusmn 029a

049 plusmn 003

Relative weight = (organ weightbody weight) times 100(119899 = 5) in each group Values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 21) = 4742 119875 lt 0007 (for relative liver weight)F (4 21) = 1594 119875 lt 01045 (for relative heart weight)119875 lt 001 as compared to vehicle treated control a119875 lt 005 as compared to fructose treated control

increased HDL-cholesterol levels as compared to fructosetreated control on the 29th day Lower dose (100mgkg) ofthe dried pulp significantly decreased serum triglyceridesVLDL and atherogenic index but did not significantly affecttotal cholesterol LDL-c and HDL-c as compared to fructosetreated control (Table 7)

324 Effect of Aloe succotrina on Liver HMGMevalonateRatio Malondialdehyde (MDA) and Reduced Glutathione(GSH) Levels Fructose (25wv) diet significantly increasedMDA and decreased GSH levels as compared to vehi-cle treated control Dried pulp of Aloe succotrina leaves(200mgkg po) and atorvastatin (10mgkg) per se signifi-cantly increased HMGmevalonate ratio and GSH levels anddecreased MDA levels as compared to fructose treated con-trol Lower dose (100mgkg) of the dried pulp significantlydecreased MDA levels but did not significantly affect GSHand HMG-CoA reductase activity as compared to fructosetreated control (Table 8)

4 Discussion

In the present study dried pulp of Aloe succotrina leavesproduced significant antihyperlipidemic effect in high fatdiet- and fructose-induced hyperlipidemic rats Rats fed withHFD or fructose for 4 successive weeks induced significanthyperlipidemia as indicated by the significant increase inserum levels of TC TG LDL-c and VLDL and decrease inserum levels of HDL-c This is supported by earlier studies[17 24 25] High fat diet had unfavorable effect on bodyweight and relative liver weight but did not significantly affectrelative heart weightThis is supported by earlier study whereHFD increased body weight and relative liver weight withoutsignificantly affecting relative heart weight [26] D-fructose(25 wv) produced increase in relative liver weight withoutsignificantly affecting body weight and relative heart weightof animals This result is also supported by the literature [17]

Fructose has been reported to induce hypertriglyc-eridemia associated with insulin resistance hyperinsuline-mia and hypertension After the absorption in GIT fructose

ISRN Pharmacology 7

Table 7 Effect of the dried pulp of Aloe succotrina leaves on serum lipid levels in fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Lipid Levels (mgdL)

TC TG HDL-c VLDL LDL-c AI(TGHDL)

1 Vehicle(1wvCMC) 10mL 6709 plusmn 274 3947 plusmn 175 3726 plusmn 183 793 plusmn 037 2183 plusmn 454 107 plusmn 006

2

Vehicle(1wvCMC)+ fructose(25wv)

10mL 8556 plusmn 437 6710 plusmn 1269 1736 plusmn 149 1342 plusmn 254 5480 plusmn 603 393 plusmn 074

3Atorvastatin +

fructose(25wv)

10mg 6432 plusmn 409a 2259 plusmn 214c 4172 plusmn 606b 452 plusmn 043c1809 plusmn 489

b060 plusmn 010

c

4Aloe succotrina+ fructose(25wv)

100mg 7197 plusmn 612 3322 plusmn 398b 4233 plusmn 548 664 plusmn 080b3853 plusmn 694 142 plusmn 032

c

5Aloe succotrina+ fructose(25wv)

200mg 6615 plusmn 216a 2474 plusmn 244c 2680 plusmn 471b 495 plusmn 049c1887 plusmn 527

b062 plusmn 009

c

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testTCmdashtotal cholesterol TGmdashtriglycerides HDL-cmdashhigh density lipoprotein- cholesterolLDL-cmdashlow density lipoprotein- cholesterol VLDLmdashvery low density lipoprotein- cholesterol AImdashatherogenic indexF (4 21) = 4344 119875 lt 00109 (for total cholesterol) F (4 21) = 8425 119875 lt 00004 (for triglycerides) F (4 21) = 6170 119875 lt 00021 (for HDL-c) F (4 21) = 8414119875 lt 00004 (for VLDL) F (4 21) = 8118 119875 lt 00005 (for LDL-c) F (4 21) =14361 119875 lt 00001 (for AI)119875 lt 005 119875 lt 001 and

119875 lt 0001 as compared to vehicle treated control a119875 lt 005 b119875 lt 001 and c119875 lt 0001 as compared to fructose treated control

Table 8 Effect of dried pulp ofAloe succotrina leaves on liverHMGmevalonate ratioMDA and reduced glutathione (GSH) levels of fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

HMGmevalonateratio

MDA levels (nmolmgtissue)

GSH levels (120583molmgtissue)

1 Vehicle(1wvCMC) 10mL 344 plusmn 122 764 plusmn 156 52455 plusmn 3589

2Vehicle

(1wvCMC) +fructose (25wv)

10mL 198 plusmn 036 4902 plusmn 092

31720 plusmn 1940

3 Atorvastatin +fructose (25wv) 10mg 617 plusmn 093

a692 plusmn 069

c44574 plusmn 1957

a

4 Aloe succotrina +fructose (25wv) 100mg 375 plusmn 078 3166 plusmn 833

a32404 plusmn 1331

5 Aloe succotrina +fructose (25wv) 200mg 566 plusmn 067

a885 plusmn 205

c42813 plusmn 3429

a

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 21) = 4140 119875 lt 00001 (for HMGmevalonate ratio)F (4 21) = 7607 119875 lt 00007 (for MDA levels)F (4 21) = 11289 119875 lt 00001 (for reduced glutathione)119875 lt 0001 as compared to vehicle treated control

a119875 lt 005 b119875 lt 005 and c

119875 lt 0001 as compared to fructose treated control

is transported via portal circulation to the liver whereit enters hepatocytes via the glucose transporter GLUT-5independently of insulin and is rapidly metabolised Fruc-tose is metabolised into ldquoglycerol-3-phosphaterdquo and ldquoacetylCoArdquo These two intermediate metabolites are then used assubstrates for glycerides synthesis contributing to VLDL-TG production in liver The exposure of liver to suchlarge quantities of fructose leads to rapid stimulation oflipogenesis and triglyceride accumulation which in turncontributes to reduced insulin sensitivity and hepatic insulinresistanceglucose intolerance [25 27]

In both HFD and fructose-induced hyperlipidemia mod-els dried pulp of Aloe succotrina leaves (200mgkg po)significantly decreased total cholesterol triglycerides LDL-c VLDL atherogenic index and liver weight and increasedHDL-c levels Antihyperlipidemic effect of the dried pulp wascomparable to atorvastatin a standard antihyperlipidemicdrug (a HMG-CoA reductase inhibitor)

Hyperlipidemia is thought to increase cholesterol con-tent and this in turn leads to generation of reactive oxy-gen species (ROS) increase in lipid peroxidation [28] anddecrease in activity of reduced glutathione It has been

8 ISRN Pharmacology

reported that overproduction of ROS can induce cellulardamage via oxidation of critical cellular components suchas membrane lipids proteins and DNA [29] The increasedlevels of total cholesterol in blood could induce arterialendothelial dysfunction and vascular endothelial injury isthe initial factor in atherosclerosis Therefore lowering lipidand protecting vascular endothelium play significant roles inpreventing atherosclerosis [30]

Previous studies showed that high fat diet [31] or fructose[25] enhanced hepatic oxidative damage due to hepaticstress resulting from the burden of high fat diet or fructosemetabolism In the present study HFD or fructose signifi-cantly increased liver MDA levels and decreased GSH levelsindicating enhancement of oxidative stressThese findings arein agreement with earlier reports [32] Dried pulp of Aloesuccotrina leaves (200mgkg) significantly increased liverGSH levels and decreased MDA levels in both HFD andfructose-induced hyperlipidemic rats thus reduced oxidativestress

To identify the possible mechanism of the antihyper-lipidemic effect of the dried pulp more specifically theactivity of HMG-CoA reductase was determined Cholesterolhomeostasis is maintained by the two processes namelycholesterol biosynthesis in which HMG-CoA reductase cat-alyzes rate limiting process and cholesterol absorption ofboth dietary cholesterol and cholesterol cleared from the liverthrough biliary secretion [33] The HMG-CoAmevalonateratio has an inverse relationship to the activity HMG-CoAreductase The result of the present study indicated that theactivity of HMG-CoA reductase is significantly inhibited bythe dried pulp of Aloe succotrina leaves (200mgkg) in bothHFD and fructose-induced hyperlipidemic rats

Hyperlipidemia is awell-known risk factor for atheroscle-rosis which is a major contributor to the pathogenesis ofheart and vascular diseases Elevated blood concentrationof cholesterol especially in LDL-c constitutes the key riskfactor for atherosclerosis [34] Atherogenic index indicatesthe deposition of foam cells or plaque or fatty infiltrationor lipids in heart coronaries aorta liver and kidneys Thehigher the atherogenic index the higher the risk of theabove organs for oxidative damage [35]Aloe succotrina leaves(200mgkg) also markedly lowered atherogenic index inboth HFD and fructose-induced hyperlipidemic rats Thusit indicated its potential in preventing atherosclerosis

5 Conclusions

Dried pulp of Aloe succotrina leaves produced significantantihyperlipidemic activity in both HFD and fructose-induced hyperlipidemic rats possibly through normalizationof serum lipid profile HMG-CoA reductase inhibitory activ-ity and amelioration of oxidative stress in liver Moreoverit also significantly decreased atherogenic index thus itmight possess potential in preventing atherosclerosis Furtherstudies are required to isolate the active constituents involvedin antihyperlipidemic activity of Aloe succotrina Thus driedpulp ofAloe succotrina leavesmay be explored for its potentialin the prevention and treatment of clinical hyperlipidemia

Conflict of Interests

Theauthors do not have any conflict of interests regarding thecontent of this research paper

Acknowledgment

The authors are thankful to Ranbaxy Laboratories PvtLtd Gurgaon (Haryana India) for providing gift sample ofatorvastatin

References

[1] G D Kolovou K K Anagnostopoulou and D V CokkinosldquoPathophysiology of dyslipidaemia in themetabolic syndromerdquoPostgraduate Medical Journal vol 81 no 956 pp 358ndash3662005

[2] R M Krauss and Y A Kesaniemi ldquoCardiovascular disease andhyperlipidaemiardquo Current Opinion in Lipidology vol 5 no 4pp 249ndash251 1994

[3] N J Stone ldquoLipidmanagement current diet and drug treatmentoptionsrdquo The American Journal of Medicine vol 101 no 4supplement 1 pp 40Sndash49S 1996

[4] Y Lin S S Mousa N Elshourbagy and S A Mousa ldquoCurrentstatus and future directions in lipid management emphasiz-ing low-density lipoproteins high-density lipoproteins andtriglycerides as targets for therapyrdquo Vascular Health and RiskManagement vol 6 no 1 pp 73ndash85 2010

[5] M Kobayashi T Kagawa K Narumi S Itagaki T Hiranoand K Iseki ldquoBicarbonate supplementation as a preventive wayin statins-induced muscle damagerdquo Journal of Pharmacy andPharmaceutical Sciences vol 11 no 1 pp 1ndash8 2008

[6] J R Guyton and H E Bays ldquoSafety considerations with niacintherapyrdquoThe American Journal of Cardiology vol 99 no 6 ppS22ndashS31 2007

[7] W C Lakey N Greyshock and J R Guyton ldquoAdverse reactionsof Achilles tendon xanthomas in three hypercholesterolemicpatients after treatment intensification with niacin and bile acidsequestrantsrdquo Journal of Clinical Lipidology vol 7 no 2 pp 178ndash181 2013

[8] M Kiskac M Zorlu M Cakirca et al ldquoA case of rhabdomy-olysis complicated with acute renal failure after resumption offenofibrate therapy a first reportrdquo Indian Journal of Pharmacol-ogy vol 45 no 3 pp 305ndash306 2013

[9] Y-Y Yeh and L Liu ldquoCholesterol-lowering effect of garlicextracts and organosulfur compounds human and animalstudiesrdquo Journal of Nutrition vol 131 no 3 pp 989Sndash993S 2001

[10] R B Singh M A Niaz and S Ghosh ldquoHypolipidemic andantioxidant effects of commiphora mukul as an adjunct todietary therapy in patients with hypercholesterolemiardquo Cardio-vascular Drugs andTherapy vol 8 no 4 pp 659ndash664 1994

[11] W W Wong E OrsquoBrian Smith J E Stuff D L Hachey WC Heird and H J Pownell ldquoCholesterol-lowering effect ofsoy protein in normocholesterolemic and hypercholesterolemicmenrdquoThe American Journal of Clinical Nutrition vol 68 no 6pp 13855Sndash13895S 1998

[12] A M Sabzghabaee M Dianatkhah N Sarrafzadegan SAsgary and A Ghannadi ldquoClinical evaluation of Nigella sativaseeds for the treatment of hyperlipidemia a randomizedplacebo controlled clinical trialrdquo Medical Archives vol 66 no3 pp 198ndash200 2012

ISRN Pharmacology 9

[13] R Sola E Bruckert R-M Valls et al ldquoSoluble fibre (Plantagoovata husk) reduces plasma low-density lipoprotein (LDL)cholesterol triglycerides insulin oxidised LDL and systolicblood pressure in hypercholesterolaemic patients a randomisedtrialrdquo Atherosclerosis vol 211 no 2 pp 630ndash637 2010

[14] R L Van Zyl and A M Viljoen ldquoIn vitro activity of Aloeextracts against Plasmodium falciparumrdquo South African Journalof Botany vol 68 no 1 pp 106ndash110 2002

[15] D K Patel R Kumar D Laloo and S Hemalatha ldquoNaturalmedicines from plant source used for therapy of diabetesmellitus an overview of its pharmacological aspectsrdquo pp 239ndash250 2012

[16] B Lu D Xia W Huang X Wu Y Zhang and Y YaoldquoHypolipidemic effect of bamboo shoot oil (P pubescens) inSprague-Dawley ratsrdquo Journal of Food Science vol 75 no 6 ppH205ndashH211 2010

[17] N Taleb-Dida D Krouf and M Bouchenak ldquoGlobulariaalypum aqueous extract decreases hypertriglyceridemia andameliorates oxidative status of the muscle kidney and heart inrats fed a high-fructose dietrdquo Nutrition Research vol 31 no 6pp 488ndash495 2011

[18] C C Allain L S Poon and C S G Chan ldquoEnzymaticdetermination of total serum cholesterolrdquo Clinical Chemistryvol 20 no 4 pp 470ndash475 1974

[19] M Burstein H R Scholnick and RMorfin ldquoRapidmethod forthe isolation of lipoproteins fromhuman serumby precipitationwith polyanionsrdquo Journal of Lipid Research vol 11 no 6 pp583ndash595 1970

[20] MWMcGowan J D Artiss D R Strandbergh and B Zak ldquoAperoxidase-coupledmethod for the colorimetric determinationof serum triglyceridesrdquo Clinical Chemistry vol 29 no 3 pp538ndash542 1983

[21] J Sedlak and R H Lindsay ldquoEstimation of total protein-bound andnonprotein sulfhydryl groups in tissuewith Ellmanrsquosreagentrdquo Analytical Biochemistry vol 25 pp 192ndash205 1968

[22] H Ohkawa N Ohishi and K Yagi ldquoAssay for lipid peroxidesin animal tissues by thiobarbituric acid reactionrdquo AnalyticalBiochemistry vol 95 no 2 pp 351ndash358 1979

[23] A Venugopala Rao and S Ramakrishnan ldquoIndirect assessmentof hydroxymethylglutaryl CoA reductase (NADPH) activity inliver tissuerdquo Clinical Chemistry vol 21 no 10 pp 1523ndash15251975

[24] A R Borate A A Suralkar S S Birje P V Malusare and PA Bangale ldquoAntihyperlipidemic effect of protocatechuic acid infructose induced hyperlipidemia in ratsrdquo International Journalof Pharma and Bio Sciences vol 2 no 4 pp 456ndash460 2011

[25] G L Kelley G Allan and S Azhar ldquoHigh dietary fructoseinduces a hepatic stress response resulting in cholesterol andlipid dysregulationrdquo Endocrinology vol 145 no 2 pp 548ndash5552004

[26] J Fu X Zhang K Liu et al ldquoHypolipidemic activity in Sprague-Dawley rats and constituents of a novel natural vegetable oilfrom Cornus wilsoniana fruitsrdquo Journal of Food Science vol 77pp 160ndash169 2012

[27] O-J Park D Cesar D Faix K Wu C H L Shackleton andM K Hellerstein ldquoMechanisms of fructose-induced hyper-triglyceridaemia in the rat Activation of hepatic pyruvatedehydrogenase through inhibition of pyruvate dehydrogenasekinaserdquo Biochemical Journal vol 282 no 3 pp 753ndash757 1992

[28] R Yazdanparast S Bahramikia and A Ardestani ldquoNasturtiumofficinale reduces oxidative stress and enhances antioxidant

capacity in hypercholesterolaemic ratsrdquo Chemico-BiologicalInteractions vol 172 no 3 pp 176ndash184 2008

[29] P G Jain S D Patil N G Haswani M V Girase and SJ Surana ldquoHypolipidemic activity of Moringa oleifera LamMoringaceae on high fat diet induced hyperlipidemia in albinoratsrdquoBrazilian Journal of Pharmacognosy vol 20 no 6 pp 969ndash973 2010

[30] MValgimigli EMerli PMalagutti et al ldquoEndothelial dysfunc-tion in acute and chronic coronary syndromes evidence for apathogenetic role of oxidative stressrdquo Archives of Biochemistryand Biophysics vol 420 no 2 pp 255ndash261 2003

[31] N P Visavadiya and A V R L Narasimhacharya ldquoHypolipi-demic and antioxidant activities of Asparagus racemosus inhypercholesteremic ratsrdquo Indian Journal of Pharmacology vol37 no 6 pp 376ndash380 2005

[32] S S Reddy P Ramatholisamma R Karuna and D Saralaku-mari ldquoPreventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress inmale Wistar ratsrdquo Food and Chemical Toxicology vol 47 no 9pp 2224ndash2229 2009

[33] T DrsquoSouza S Mengi S Hassarajani and S ChattopadhayayldquoEfficacy study of the bioactive fraction (F-3) of Acorus calamusin hyperlipidemiardquo Indian Journal of Pharmacology vol 39 no4 pp 196ndash200 2007

[34] P O Bonetti D R Holmes Jr A Lerman and G W BarsnessldquoEnhanced external counterpulsation for ischemic heart dis-ease whatrsquos behind the curtainrdquo Journal of the AmericanCollegeof Cardiology vol 41 no 11 pp 1918ndash1925 2003

[35] L K Mehta R Balaraman A H Amin P A Bafna and OD Gulati ldquoEffect of fruits of Moringa oleifera on the lipidprofile of normal and hypercholesterolaemic rabbitsrdquo Journal ofEthnopharmacology vol 86 no 2-3 pp 191ndash195 2003

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of AddictionHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AnesthesiologyResearch and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

ISRN Pharmacology 7

Table 7 Effect of the dried pulp of Aloe succotrina leaves on serum lipid levels in fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

Lipid Levels (mgdL)

TC TG HDL-c VLDL LDL-c AI(TGHDL)

1 Vehicle(1wvCMC) 10mL 6709 plusmn 274 3947 plusmn 175 3726 plusmn 183 793 plusmn 037 2183 plusmn 454 107 plusmn 006

2

Vehicle(1wvCMC)+ fructose(25wv)

10mL 8556 plusmn 437 6710 plusmn 1269 1736 plusmn 149 1342 plusmn 254 5480 plusmn 603 393 plusmn 074

3Atorvastatin +

fructose(25wv)

10mg 6432 plusmn 409a 2259 plusmn 214c 4172 plusmn 606b 452 plusmn 043c1809 plusmn 489

b060 plusmn 010

c

4Aloe succotrina+ fructose(25wv)

100mg 7197 plusmn 612 3322 plusmn 398b 4233 plusmn 548 664 plusmn 080b3853 plusmn 694 142 plusmn 032

c

5Aloe succotrina+ fructose(25wv)

200mg 6615 plusmn 216a 2474 plusmn 244c 2680 plusmn 471b 495 plusmn 049c1887 plusmn 527

b062 plusmn 009

c

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testTCmdashtotal cholesterol TGmdashtriglycerides HDL-cmdashhigh density lipoprotein- cholesterolLDL-cmdashlow density lipoprotein- cholesterol VLDLmdashvery low density lipoprotein- cholesterol AImdashatherogenic indexF (4 21) = 4344 119875 lt 00109 (for total cholesterol) F (4 21) = 8425 119875 lt 00004 (for triglycerides) F (4 21) = 6170 119875 lt 00021 (for HDL-c) F (4 21) = 8414119875 lt 00004 (for VLDL) F (4 21) = 8118 119875 lt 00005 (for LDL-c) F (4 21) =14361 119875 lt 00001 (for AI)119875 lt 005 119875 lt 001 and

119875 lt 0001 as compared to vehicle treated control a119875 lt 005 b119875 lt 001 and c119875 lt 0001 as compared to fructose treated control

Table 8 Effect of dried pulp ofAloe succotrina leaves on liverHMGmevalonate ratioMDA and reduced glutathione (GSH) levels of fructose-induced hyperlipidemic rats

Groupnumber

Treatment(po)

Dose(kgminus1)

HMGmevalonateratio

MDA levels (nmolmgtissue)

GSH levels (120583molmgtissue)

1 Vehicle(1wvCMC) 10mL 344 plusmn 122 764 plusmn 156 52455 plusmn 3589

2Vehicle

(1wvCMC) +fructose (25wv)

10mL 198 plusmn 036 4902 plusmn 092

31720 plusmn 1940

3 Atorvastatin +fructose (25wv) 10mg 617 plusmn 093

a692 plusmn 069

c44574 plusmn 1957

a

4 Aloe succotrina +fructose (25wv) 100mg 375 plusmn 078 3166 plusmn 833

a32404 plusmn 1331

5 Aloe succotrina +fructose (25wv) 200mg 566 plusmn 067

a885 plusmn 205

c42813 plusmn 3429

a

(119899 = 5) in each group values are in Mean plusmn SEM data was analyzed by one-way ANOVA followed by Tukey-Kramer multiple comparison testF (4 21) = 4140 119875 lt 00001 (for HMGmevalonate ratio)F (4 21) = 7607 119875 lt 00007 (for MDA levels)F (4 21) = 11289 119875 lt 00001 (for reduced glutathione)119875 lt 0001 as compared to vehicle treated control

a119875 lt 005 b119875 lt 005 and c

119875 lt 0001 as compared to fructose treated control

is transported via portal circulation to the liver whereit enters hepatocytes via the glucose transporter GLUT-5independently of insulin and is rapidly metabolised Fruc-tose is metabolised into ldquoglycerol-3-phosphaterdquo and ldquoacetylCoArdquo These two intermediate metabolites are then used assubstrates for glycerides synthesis contributing to VLDL-TG production in liver The exposure of liver to suchlarge quantities of fructose leads to rapid stimulation oflipogenesis and triglyceride accumulation which in turncontributes to reduced insulin sensitivity and hepatic insulinresistanceglucose intolerance [25 27]

In both HFD and fructose-induced hyperlipidemia mod-els dried pulp of Aloe succotrina leaves (200mgkg po)significantly decreased total cholesterol triglycerides LDL-c VLDL atherogenic index and liver weight and increasedHDL-c levels Antihyperlipidemic effect of the dried pulp wascomparable to atorvastatin a standard antihyperlipidemicdrug (a HMG-CoA reductase inhibitor)

Hyperlipidemia is thought to increase cholesterol con-tent and this in turn leads to generation of reactive oxy-gen species (ROS) increase in lipid peroxidation [28] anddecrease in activity of reduced glutathione It has been

8 ISRN Pharmacology

reported that overproduction of ROS can induce cellulardamage via oxidation of critical cellular components suchas membrane lipids proteins and DNA [29] The increasedlevels of total cholesterol in blood could induce arterialendothelial dysfunction and vascular endothelial injury isthe initial factor in atherosclerosis Therefore lowering lipidand protecting vascular endothelium play significant roles inpreventing atherosclerosis [30]

Previous studies showed that high fat diet [31] or fructose[25] enhanced hepatic oxidative damage due to hepaticstress resulting from the burden of high fat diet or fructosemetabolism In the present study HFD or fructose signifi-cantly increased liver MDA levels and decreased GSH levelsindicating enhancement of oxidative stressThese findings arein agreement with earlier reports [32] Dried pulp of Aloesuccotrina leaves (200mgkg) significantly increased liverGSH levels and decreased MDA levels in both HFD andfructose-induced hyperlipidemic rats thus reduced oxidativestress

To identify the possible mechanism of the antihyper-lipidemic effect of the dried pulp more specifically theactivity of HMG-CoA reductase was determined Cholesterolhomeostasis is maintained by the two processes namelycholesterol biosynthesis in which HMG-CoA reductase cat-alyzes rate limiting process and cholesterol absorption ofboth dietary cholesterol and cholesterol cleared from the liverthrough biliary secretion [33] The HMG-CoAmevalonateratio has an inverse relationship to the activity HMG-CoAreductase The result of the present study indicated that theactivity of HMG-CoA reductase is significantly inhibited bythe dried pulp of Aloe succotrina leaves (200mgkg) in bothHFD and fructose-induced hyperlipidemic rats

Hyperlipidemia is awell-known risk factor for atheroscle-rosis which is a major contributor to the pathogenesis ofheart and vascular diseases Elevated blood concentrationof cholesterol especially in LDL-c constitutes the key riskfactor for atherosclerosis [34] Atherogenic index indicatesthe deposition of foam cells or plaque or fatty infiltrationor lipids in heart coronaries aorta liver and kidneys Thehigher the atherogenic index the higher the risk of theabove organs for oxidative damage [35]Aloe succotrina leaves(200mgkg) also markedly lowered atherogenic index inboth HFD and fructose-induced hyperlipidemic rats Thusit indicated its potential in preventing atherosclerosis

5 Conclusions

Dried pulp of Aloe succotrina leaves produced significantantihyperlipidemic activity in both HFD and fructose-induced hyperlipidemic rats possibly through normalizationof serum lipid profile HMG-CoA reductase inhibitory activ-ity and amelioration of oxidative stress in liver Moreoverit also significantly decreased atherogenic index thus itmight possess potential in preventing atherosclerosis Furtherstudies are required to isolate the active constituents involvedin antihyperlipidemic activity of Aloe succotrina Thus driedpulp ofAloe succotrina leavesmay be explored for its potentialin the prevention and treatment of clinical hyperlipidemia

Conflict of Interests

Theauthors do not have any conflict of interests regarding thecontent of this research paper

Acknowledgment

The authors are thankful to Ranbaxy Laboratories PvtLtd Gurgaon (Haryana India) for providing gift sample ofatorvastatin

References

[1] G D Kolovou K K Anagnostopoulou and D V CokkinosldquoPathophysiology of dyslipidaemia in themetabolic syndromerdquoPostgraduate Medical Journal vol 81 no 956 pp 358ndash3662005

[2] R M Krauss and Y A Kesaniemi ldquoCardiovascular disease andhyperlipidaemiardquo Current Opinion in Lipidology vol 5 no 4pp 249ndash251 1994

[3] N J Stone ldquoLipidmanagement current diet and drug treatmentoptionsrdquo The American Journal of Medicine vol 101 no 4supplement 1 pp 40Sndash49S 1996

[4] Y Lin S S Mousa N Elshourbagy and S A Mousa ldquoCurrentstatus and future directions in lipid management emphasiz-ing low-density lipoproteins high-density lipoproteins andtriglycerides as targets for therapyrdquo Vascular Health and RiskManagement vol 6 no 1 pp 73ndash85 2010

[5] M Kobayashi T Kagawa K Narumi S Itagaki T Hiranoand K Iseki ldquoBicarbonate supplementation as a preventive wayin statins-induced muscle damagerdquo Journal of Pharmacy andPharmaceutical Sciences vol 11 no 1 pp 1ndash8 2008

[6] J R Guyton and H E Bays ldquoSafety considerations with niacintherapyrdquoThe American Journal of Cardiology vol 99 no 6 ppS22ndashS31 2007

[7] W C Lakey N Greyshock and J R Guyton ldquoAdverse reactionsof Achilles tendon xanthomas in three hypercholesterolemicpatients after treatment intensification with niacin and bile acidsequestrantsrdquo Journal of Clinical Lipidology vol 7 no 2 pp 178ndash181 2013

[8] M Kiskac M Zorlu M Cakirca et al ldquoA case of rhabdomy-olysis complicated with acute renal failure after resumption offenofibrate therapy a first reportrdquo Indian Journal of Pharmacol-ogy vol 45 no 3 pp 305ndash306 2013

[9] Y-Y Yeh and L Liu ldquoCholesterol-lowering effect of garlicextracts and organosulfur compounds human and animalstudiesrdquo Journal of Nutrition vol 131 no 3 pp 989Sndash993S 2001

[10] R B Singh M A Niaz and S Ghosh ldquoHypolipidemic andantioxidant effects of commiphora mukul as an adjunct todietary therapy in patients with hypercholesterolemiardquo Cardio-vascular Drugs andTherapy vol 8 no 4 pp 659ndash664 1994

[11] W W Wong E OrsquoBrian Smith J E Stuff D L Hachey WC Heird and H J Pownell ldquoCholesterol-lowering effect ofsoy protein in normocholesterolemic and hypercholesterolemicmenrdquoThe American Journal of Clinical Nutrition vol 68 no 6pp 13855Sndash13895S 1998

[12] A M Sabzghabaee M Dianatkhah N Sarrafzadegan SAsgary and A Ghannadi ldquoClinical evaluation of Nigella sativaseeds for the treatment of hyperlipidemia a randomizedplacebo controlled clinical trialrdquo Medical Archives vol 66 no3 pp 198ndash200 2012

ISRN Pharmacology 9

[13] R Sola E Bruckert R-M Valls et al ldquoSoluble fibre (Plantagoovata husk) reduces plasma low-density lipoprotein (LDL)cholesterol triglycerides insulin oxidised LDL and systolicblood pressure in hypercholesterolaemic patients a randomisedtrialrdquo Atherosclerosis vol 211 no 2 pp 630ndash637 2010

[14] R L Van Zyl and A M Viljoen ldquoIn vitro activity of Aloeextracts against Plasmodium falciparumrdquo South African Journalof Botany vol 68 no 1 pp 106ndash110 2002

[15] D K Patel R Kumar D Laloo and S Hemalatha ldquoNaturalmedicines from plant source used for therapy of diabetesmellitus an overview of its pharmacological aspectsrdquo pp 239ndash250 2012

[16] B Lu D Xia W Huang X Wu Y Zhang and Y YaoldquoHypolipidemic effect of bamboo shoot oil (P pubescens) inSprague-Dawley ratsrdquo Journal of Food Science vol 75 no 6 ppH205ndashH211 2010

[17] N Taleb-Dida D Krouf and M Bouchenak ldquoGlobulariaalypum aqueous extract decreases hypertriglyceridemia andameliorates oxidative status of the muscle kidney and heart inrats fed a high-fructose dietrdquo Nutrition Research vol 31 no 6pp 488ndash495 2011

[18] C C Allain L S Poon and C S G Chan ldquoEnzymaticdetermination of total serum cholesterolrdquo Clinical Chemistryvol 20 no 4 pp 470ndash475 1974

[19] M Burstein H R Scholnick and RMorfin ldquoRapidmethod forthe isolation of lipoproteins fromhuman serumby precipitationwith polyanionsrdquo Journal of Lipid Research vol 11 no 6 pp583ndash595 1970

[20] MWMcGowan J D Artiss D R Strandbergh and B Zak ldquoAperoxidase-coupledmethod for the colorimetric determinationof serum triglyceridesrdquo Clinical Chemistry vol 29 no 3 pp538ndash542 1983

[21] J Sedlak and R H Lindsay ldquoEstimation of total protein-bound andnonprotein sulfhydryl groups in tissuewith Ellmanrsquosreagentrdquo Analytical Biochemistry vol 25 pp 192ndash205 1968

[22] H Ohkawa N Ohishi and K Yagi ldquoAssay for lipid peroxidesin animal tissues by thiobarbituric acid reactionrdquo AnalyticalBiochemistry vol 95 no 2 pp 351ndash358 1979

[23] A Venugopala Rao and S Ramakrishnan ldquoIndirect assessmentof hydroxymethylglutaryl CoA reductase (NADPH) activity inliver tissuerdquo Clinical Chemistry vol 21 no 10 pp 1523ndash15251975

[24] A R Borate A A Suralkar S S Birje P V Malusare and PA Bangale ldquoAntihyperlipidemic effect of protocatechuic acid infructose induced hyperlipidemia in ratsrdquo International Journalof Pharma and Bio Sciences vol 2 no 4 pp 456ndash460 2011

[25] G L Kelley G Allan and S Azhar ldquoHigh dietary fructoseinduces a hepatic stress response resulting in cholesterol andlipid dysregulationrdquo Endocrinology vol 145 no 2 pp 548ndash5552004

[26] J Fu X Zhang K Liu et al ldquoHypolipidemic activity in Sprague-Dawley rats and constituents of a novel natural vegetable oilfrom Cornus wilsoniana fruitsrdquo Journal of Food Science vol 77pp 160ndash169 2012

[27] O-J Park D Cesar D Faix K Wu C H L Shackleton andM K Hellerstein ldquoMechanisms of fructose-induced hyper-triglyceridaemia in the rat Activation of hepatic pyruvatedehydrogenase through inhibition of pyruvate dehydrogenasekinaserdquo Biochemical Journal vol 282 no 3 pp 753ndash757 1992

[28] R Yazdanparast S Bahramikia and A Ardestani ldquoNasturtiumofficinale reduces oxidative stress and enhances antioxidant

capacity in hypercholesterolaemic ratsrdquo Chemico-BiologicalInteractions vol 172 no 3 pp 176ndash184 2008

[29] P G Jain S D Patil N G Haswani M V Girase and SJ Surana ldquoHypolipidemic activity of Moringa oleifera LamMoringaceae on high fat diet induced hyperlipidemia in albinoratsrdquoBrazilian Journal of Pharmacognosy vol 20 no 6 pp 969ndash973 2010

[30] MValgimigli EMerli PMalagutti et al ldquoEndothelial dysfunc-tion in acute and chronic coronary syndromes evidence for apathogenetic role of oxidative stressrdquo Archives of Biochemistryand Biophysics vol 420 no 2 pp 255ndash261 2003

[31] N P Visavadiya and A V R L Narasimhacharya ldquoHypolipi-demic and antioxidant activities of Asparagus racemosus inhypercholesteremic ratsrdquo Indian Journal of Pharmacology vol37 no 6 pp 376ndash380 2005

[32] S S Reddy P Ramatholisamma R Karuna and D Saralaku-mari ldquoPreventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress inmale Wistar ratsrdquo Food and Chemical Toxicology vol 47 no 9pp 2224ndash2229 2009

[33] T DrsquoSouza S Mengi S Hassarajani and S ChattopadhayayldquoEfficacy study of the bioactive fraction (F-3) of Acorus calamusin hyperlipidemiardquo Indian Journal of Pharmacology vol 39 no4 pp 196ndash200 2007

[34] P O Bonetti D R Holmes Jr A Lerman and G W BarsnessldquoEnhanced external counterpulsation for ischemic heart dis-ease whatrsquos behind the curtainrdquo Journal of the AmericanCollegeof Cardiology vol 41 no 11 pp 1918ndash1925 2003

[35] L K Mehta R Balaraman A H Amin P A Bafna and OD Gulati ldquoEffect of fruits of Moringa oleifera on the lipidprofile of normal and hypercholesterolaemic rabbitsrdquo Journal ofEthnopharmacology vol 86 no 2-3 pp 191ndash195 2003

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of AddictionHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AnesthesiologyResearch and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

8 ISRN Pharmacology

reported that overproduction of ROS can induce cellulardamage via oxidation of critical cellular components suchas membrane lipids proteins and DNA [29] The increasedlevels of total cholesterol in blood could induce arterialendothelial dysfunction and vascular endothelial injury isthe initial factor in atherosclerosis Therefore lowering lipidand protecting vascular endothelium play significant roles inpreventing atherosclerosis [30]

Previous studies showed that high fat diet [31] or fructose[25] enhanced hepatic oxidative damage due to hepaticstress resulting from the burden of high fat diet or fructosemetabolism In the present study HFD or fructose signifi-cantly increased liver MDA levels and decreased GSH levelsindicating enhancement of oxidative stressThese findings arein agreement with earlier reports [32] Dried pulp of Aloesuccotrina leaves (200mgkg) significantly increased liverGSH levels and decreased MDA levels in both HFD andfructose-induced hyperlipidemic rats thus reduced oxidativestress

To identify the possible mechanism of the antihyper-lipidemic effect of the dried pulp more specifically theactivity of HMG-CoA reductase was determined Cholesterolhomeostasis is maintained by the two processes namelycholesterol biosynthesis in which HMG-CoA reductase cat-alyzes rate limiting process and cholesterol absorption ofboth dietary cholesterol and cholesterol cleared from the liverthrough biliary secretion [33] The HMG-CoAmevalonateratio has an inverse relationship to the activity HMG-CoAreductase The result of the present study indicated that theactivity of HMG-CoA reductase is significantly inhibited bythe dried pulp of Aloe succotrina leaves (200mgkg) in bothHFD and fructose-induced hyperlipidemic rats

Hyperlipidemia is awell-known risk factor for atheroscle-rosis which is a major contributor to the pathogenesis ofheart and vascular diseases Elevated blood concentrationof cholesterol especially in LDL-c constitutes the key riskfactor for atherosclerosis [34] Atherogenic index indicatesthe deposition of foam cells or plaque or fatty infiltrationor lipids in heart coronaries aorta liver and kidneys Thehigher the atherogenic index the higher the risk of theabove organs for oxidative damage [35]Aloe succotrina leaves(200mgkg) also markedly lowered atherogenic index inboth HFD and fructose-induced hyperlipidemic rats Thusit indicated its potential in preventing atherosclerosis

5 Conclusions

Dried pulp of Aloe succotrina leaves produced significantantihyperlipidemic activity in both HFD and fructose-induced hyperlipidemic rats possibly through normalizationof serum lipid profile HMG-CoA reductase inhibitory activ-ity and amelioration of oxidative stress in liver Moreoverit also significantly decreased atherogenic index thus itmight possess potential in preventing atherosclerosis Furtherstudies are required to isolate the active constituents involvedin antihyperlipidemic activity of Aloe succotrina Thus driedpulp ofAloe succotrina leavesmay be explored for its potentialin the prevention and treatment of clinical hyperlipidemia

Conflict of Interests

Theauthors do not have any conflict of interests regarding thecontent of this research paper

Acknowledgment

The authors are thankful to Ranbaxy Laboratories PvtLtd Gurgaon (Haryana India) for providing gift sample ofatorvastatin

References

[1] G D Kolovou K K Anagnostopoulou and D V CokkinosldquoPathophysiology of dyslipidaemia in themetabolic syndromerdquoPostgraduate Medical Journal vol 81 no 956 pp 358ndash3662005

[2] R M Krauss and Y A Kesaniemi ldquoCardiovascular disease andhyperlipidaemiardquo Current Opinion in Lipidology vol 5 no 4pp 249ndash251 1994

[3] N J Stone ldquoLipidmanagement current diet and drug treatmentoptionsrdquo The American Journal of Medicine vol 101 no 4supplement 1 pp 40Sndash49S 1996

[4] Y Lin S S Mousa N Elshourbagy and S A Mousa ldquoCurrentstatus and future directions in lipid management emphasiz-ing low-density lipoproteins high-density lipoproteins andtriglycerides as targets for therapyrdquo Vascular Health and RiskManagement vol 6 no 1 pp 73ndash85 2010

[5] M Kobayashi T Kagawa K Narumi S Itagaki T Hiranoand K Iseki ldquoBicarbonate supplementation as a preventive wayin statins-induced muscle damagerdquo Journal of Pharmacy andPharmaceutical Sciences vol 11 no 1 pp 1ndash8 2008

[6] J R Guyton and H E Bays ldquoSafety considerations with niacintherapyrdquoThe American Journal of Cardiology vol 99 no 6 ppS22ndashS31 2007

[7] W C Lakey N Greyshock and J R Guyton ldquoAdverse reactionsof Achilles tendon xanthomas in three hypercholesterolemicpatients after treatment intensification with niacin and bile acidsequestrantsrdquo Journal of Clinical Lipidology vol 7 no 2 pp 178ndash181 2013

[8] M Kiskac M Zorlu M Cakirca et al ldquoA case of rhabdomy-olysis complicated with acute renal failure after resumption offenofibrate therapy a first reportrdquo Indian Journal of Pharmacol-ogy vol 45 no 3 pp 305ndash306 2013

[9] Y-Y Yeh and L Liu ldquoCholesterol-lowering effect of garlicextracts and organosulfur compounds human and animalstudiesrdquo Journal of Nutrition vol 131 no 3 pp 989Sndash993S 2001

[10] R B Singh M A Niaz and S Ghosh ldquoHypolipidemic andantioxidant effects of commiphora mukul as an adjunct todietary therapy in patients with hypercholesterolemiardquo Cardio-vascular Drugs andTherapy vol 8 no 4 pp 659ndash664 1994

[11] W W Wong E OrsquoBrian Smith J E Stuff D L Hachey WC Heird and H J Pownell ldquoCholesterol-lowering effect ofsoy protein in normocholesterolemic and hypercholesterolemicmenrdquoThe American Journal of Clinical Nutrition vol 68 no 6pp 13855Sndash13895S 1998

[12] A M Sabzghabaee M Dianatkhah N Sarrafzadegan SAsgary and A Ghannadi ldquoClinical evaluation of Nigella sativaseeds for the treatment of hyperlipidemia a randomizedplacebo controlled clinical trialrdquo Medical Archives vol 66 no3 pp 198ndash200 2012

ISRN Pharmacology 9

[13] R Sola E Bruckert R-M Valls et al ldquoSoluble fibre (Plantagoovata husk) reduces plasma low-density lipoprotein (LDL)cholesterol triglycerides insulin oxidised LDL and systolicblood pressure in hypercholesterolaemic patients a randomisedtrialrdquo Atherosclerosis vol 211 no 2 pp 630ndash637 2010

[14] R L Van Zyl and A M Viljoen ldquoIn vitro activity of Aloeextracts against Plasmodium falciparumrdquo South African Journalof Botany vol 68 no 1 pp 106ndash110 2002

[15] D K Patel R Kumar D Laloo and S Hemalatha ldquoNaturalmedicines from plant source used for therapy of diabetesmellitus an overview of its pharmacological aspectsrdquo pp 239ndash250 2012

[16] B Lu D Xia W Huang X Wu Y Zhang and Y YaoldquoHypolipidemic effect of bamboo shoot oil (P pubescens) inSprague-Dawley ratsrdquo Journal of Food Science vol 75 no 6 ppH205ndashH211 2010

[17] N Taleb-Dida D Krouf and M Bouchenak ldquoGlobulariaalypum aqueous extract decreases hypertriglyceridemia andameliorates oxidative status of the muscle kidney and heart inrats fed a high-fructose dietrdquo Nutrition Research vol 31 no 6pp 488ndash495 2011

[18] C C Allain L S Poon and C S G Chan ldquoEnzymaticdetermination of total serum cholesterolrdquo Clinical Chemistryvol 20 no 4 pp 470ndash475 1974

[19] M Burstein H R Scholnick and RMorfin ldquoRapidmethod forthe isolation of lipoproteins fromhuman serumby precipitationwith polyanionsrdquo Journal of Lipid Research vol 11 no 6 pp583ndash595 1970

[20] MWMcGowan J D Artiss D R Strandbergh and B Zak ldquoAperoxidase-coupledmethod for the colorimetric determinationof serum triglyceridesrdquo Clinical Chemistry vol 29 no 3 pp538ndash542 1983

[21] J Sedlak and R H Lindsay ldquoEstimation of total protein-bound andnonprotein sulfhydryl groups in tissuewith Ellmanrsquosreagentrdquo Analytical Biochemistry vol 25 pp 192ndash205 1968

[22] H Ohkawa N Ohishi and K Yagi ldquoAssay for lipid peroxidesin animal tissues by thiobarbituric acid reactionrdquo AnalyticalBiochemistry vol 95 no 2 pp 351ndash358 1979

[23] A Venugopala Rao and S Ramakrishnan ldquoIndirect assessmentof hydroxymethylglutaryl CoA reductase (NADPH) activity inliver tissuerdquo Clinical Chemistry vol 21 no 10 pp 1523ndash15251975

[24] A R Borate A A Suralkar S S Birje P V Malusare and PA Bangale ldquoAntihyperlipidemic effect of protocatechuic acid infructose induced hyperlipidemia in ratsrdquo International Journalof Pharma and Bio Sciences vol 2 no 4 pp 456ndash460 2011

[25] G L Kelley G Allan and S Azhar ldquoHigh dietary fructoseinduces a hepatic stress response resulting in cholesterol andlipid dysregulationrdquo Endocrinology vol 145 no 2 pp 548ndash5552004

[26] J Fu X Zhang K Liu et al ldquoHypolipidemic activity in Sprague-Dawley rats and constituents of a novel natural vegetable oilfrom Cornus wilsoniana fruitsrdquo Journal of Food Science vol 77pp 160ndash169 2012

[27] O-J Park D Cesar D Faix K Wu C H L Shackleton andM K Hellerstein ldquoMechanisms of fructose-induced hyper-triglyceridaemia in the rat Activation of hepatic pyruvatedehydrogenase through inhibition of pyruvate dehydrogenasekinaserdquo Biochemical Journal vol 282 no 3 pp 753ndash757 1992

[28] R Yazdanparast S Bahramikia and A Ardestani ldquoNasturtiumofficinale reduces oxidative stress and enhances antioxidant

capacity in hypercholesterolaemic ratsrdquo Chemico-BiologicalInteractions vol 172 no 3 pp 176ndash184 2008

[29] P G Jain S D Patil N G Haswani M V Girase and SJ Surana ldquoHypolipidemic activity of Moringa oleifera LamMoringaceae on high fat diet induced hyperlipidemia in albinoratsrdquoBrazilian Journal of Pharmacognosy vol 20 no 6 pp 969ndash973 2010

[30] MValgimigli EMerli PMalagutti et al ldquoEndothelial dysfunc-tion in acute and chronic coronary syndromes evidence for apathogenetic role of oxidative stressrdquo Archives of Biochemistryand Biophysics vol 420 no 2 pp 255ndash261 2003

[31] N P Visavadiya and A V R L Narasimhacharya ldquoHypolipi-demic and antioxidant activities of Asparagus racemosus inhypercholesteremic ratsrdquo Indian Journal of Pharmacology vol37 no 6 pp 376ndash380 2005

[32] S S Reddy P Ramatholisamma R Karuna and D Saralaku-mari ldquoPreventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress inmale Wistar ratsrdquo Food and Chemical Toxicology vol 47 no 9pp 2224ndash2229 2009

[33] T DrsquoSouza S Mengi S Hassarajani and S ChattopadhayayldquoEfficacy study of the bioactive fraction (F-3) of Acorus calamusin hyperlipidemiardquo Indian Journal of Pharmacology vol 39 no4 pp 196ndash200 2007

[34] P O Bonetti D R Holmes Jr A Lerman and G W BarsnessldquoEnhanced external counterpulsation for ischemic heart dis-ease whatrsquos behind the curtainrdquo Journal of the AmericanCollegeof Cardiology vol 41 no 11 pp 1918ndash1925 2003

[35] L K Mehta R Balaraman A H Amin P A Bafna and OD Gulati ldquoEffect of fruits of Moringa oleifera on the lipidprofile of normal and hypercholesterolaemic rabbitsrdquo Journal ofEthnopharmacology vol 86 no 2-3 pp 191ndash195 2003

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of AddictionHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AnesthesiologyResearch and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

ISRN Pharmacology 9

[13] R Sola E Bruckert R-M Valls et al ldquoSoluble fibre (Plantagoovata husk) reduces plasma low-density lipoprotein (LDL)cholesterol triglycerides insulin oxidised LDL and systolicblood pressure in hypercholesterolaemic patients a randomisedtrialrdquo Atherosclerosis vol 211 no 2 pp 630ndash637 2010

[14] R L Van Zyl and A M Viljoen ldquoIn vitro activity of Aloeextracts against Plasmodium falciparumrdquo South African Journalof Botany vol 68 no 1 pp 106ndash110 2002

[15] D K Patel R Kumar D Laloo and S Hemalatha ldquoNaturalmedicines from plant source used for therapy of diabetesmellitus an overview of its pharmacological aspectsrdquo pp 239ndash250 2012

[16] B Lu D Xia W Huang X Wu Y Zhang and Y YaoldquoHypolipidemic effect of bamboo shoot oil (P pubescens) inSprague-Dawley ratsrdquo Journal of Food Science vol 75 no 6 ppH205ndashH211 2010

[17] N Taleb-Dida D Krouf and M Bouchenak ldquoGlobulariaalypum aqueous extract decreases hypertriglyceridemia andameliorates oxidative status of the muscle kidney and heart inrats fed a high-fructose dietrdquo Nutrition Research vol 31 no 6pp 488ndash495 2011

[18] C C Allain L S Poon and C S G Chan ldquoEnzymaticdetermination of total serum cholesterolrdquo Clinical Chemistryvol 20 no 4 pp 470ndash475 1974

[19] M Burstein H R Scholnick and RMorfin ldquoRapidmethod forthe isolation of lipoproteins fromhuman serumby precipitationwith polyanionsrdquo Journal of Lipid Research vol 11 no 6 pp583ndash595 1970

[20] MWMcGowan J D Artiss D R Strandbergh and B Zak ldquoAperoxidase-coupledmethod for the colorimetric determinationof serum triglyceridesrdquo Clinical Chemistry vol 29 no 3 pp538ndash542 1983

[21] J Sedlak and R H Lindsay ldquoEstimation of total protein-bound andnonprotein sulfhydryl groups in tissuewith Ellmanrsquosreagentrdquo Analytical Biochemistry vol 25 pp 192ndash205 1968

[22] H Ohkawa N Ohishi and K Yagi ldquoAssay for lipid peroxidesin animal tissues by thiobarbituric acid reactionrdquo AnalyticalBiochemistry vol 95 no 2 pp 351ndash358 1979

[23] A Venugopala Rao and S Ramakrishnan ldquoIndirect assessmentof hydroxymethylglutaryl CoA reductase (NADPH) activity inliver tissuerdquo Clinical Chemistry vol 21 no 10 pp 1523ndash15251975

[24] A R Borate A A Suralkar S S Birje P V Malusare and PA Bangale ldquoAntihyperlipidemic effect of protocatechuic acid infructose induced hyperlipidemia in ratsrdquo International Journalof Pharma and Bio Sciences vol 2 no 4 pp 456ndash460 2011

[25] G L Kelley G Allan and S Azhar ldquoHigh dietary fructoseinduces a hepatic stress response resulting in cholesterol andlipid dysregulationrdquo Endocrinology vol 145 no 2 pp 548ndash5552004

[26] J Fu X Zhang K Liu et al ldquoHypolipidemic activity in Sprague-Dawley rats and constituents of a novel natural vegetable oilfrom Cornus wilsoniana fruitsrdquo Journal of Food Science vol 77pp 160ndash169 2012

[27] O-J Park D Cesar D Faix K Wu C H L Shackleton andM K Hellerstein ldquoMechanisms of fructose-induced hyper-triglyceridaemia in the rat Activation of hepatic pyruvatedehydrogenase through inhibition of pyruvate dehydrogenasekinaserdquo Biochemical Journal vol 282 no 3 pp 753ndash757 1992

[28] R Yazdanparast S Bahramikia and A Ardestani ldquoNasturtiumofficinale reduces oxidative stress and enhances antioxidant

capacity in hypercholesterolaemic ratsrdquo Chemico-BiologicalInteractions vol 172 no 3 pp 176ndash184 2008

[29] P G Jain S D Patil N G Haswani M V Girase and SJ Surana ldquoHypolipidemic activity of Moringa oleifera LamMoringaceae on high fat diet induced hyperlipidemia in albinoratsrdquoBrazilian Journal of Pharmacognosy vol 20 no 6 pp 969ndash973 2010

[30] MValgimigli EMerli PMalagutti et al ldquoEndothelial dysfunc-tion in acute and chronic coronary syndromes evidence for apathogenetic role of oxidative stressrdquo Archives of Biochemistryand Biophysics vol 420 no 2 pp 255ndash261 2003

[31] N P Visavadiya and A V R L Narasimhacharya ldquoHypolipi-demic and antioxidant activities of Asparagus racemosus inhypercholesteremic ratsrdquo Indian Journal of Pharmacology vol37 no 6 pp 376ndash380 2005

[32] S S Reddy P Ramatholisamma R Karuna and D Saralaku-mari ldquoPreventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress inmale Wistar ratsrdquo Food and Chemical Toxicology vol 47 no 9pp 2224ndash2229 2009

[33] T DrsquoSouza S Mengi S Hassarajani and S ChattopadhayayldquoEfficacy study of the bioactive fraction (F-3) of Acorus calamusin hyperlipidemiardquo Indian Journal of Pharmacology vol 39 no4 pp 196ndash200 2007

[34] P O Bonetti D R Holmes Jr A Lerman and G W BarsnessldquoEnhanced external counterpulsation for ischemic heart dis-ease whatrsquos behind the curtainrdquo Journal of the AmericanCollegeof Cardiology vol 41 no 11 pp 1918ndash1925 2003

[35] L K Mehta R Balaraman A H Amin P A Bafna and OD Gulati ldquoEffect of fruits of Moringa oleifera on the lipidprofile of normal and hypercholesterolaemic rabbitsrdquo Journal ofEthnopharmacology vol 86 no 2-3 pp 191ndash195 2003

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of AddictionHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AnesthesiologyResearch and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of AddictionHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AnesthesiologyResearch and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of