Lowering Cholesterol UPH Rev 2012

5/21/2018 Lowering Cholesterol UPH Rev 2012

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Lowering Cholesterol Natural

Products Drug Development

Leonardus B.S. Kardono

University of Indonesia, July 14, 2013


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INTRODUCTION

Cardiovascular diseases are the leading

cause of death in Indonesia where one of

the common pathological substrate

underlying this process is atherosclerosis.

The OxLDL plays a key role in the

initiation and progression of

atherosclerosis (Ross, 1993). One of thepotentially atherogenic properties of

OxLDL is its cytotoxicity to the cells of the

artery wall


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INTRODUCTION

Statins remain the first-line therapy for

preventing atherosclerotic cardiovascular

diseases, but undesirable side effects have

received much attention (Rosenson, 2004),however, some of them showed the

disadvantages, such as being hepatotoxic and

increased the blood sugar level. So the search

for new and safe antiatherosclerotic drugs hasprompted researchers to investigate the efficacy

of natural products (Wang et al., 2006).


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SEARCH FOR LOWERING

CHOLESTEROL

Search from Marine and Terrestrial Natural Products

(Medicinal Plants (Jamu), Jelly Fishes or Fermented

Microbes)

In the past mostly was conducted using animal model,

classical pharmacology.

Anticholesterol activity was evaluated in the laboratory or

by anticholesterol kits.

Some were studied in silico (Computer aided drug

design)

Currently the search is studied through molecular

biology, such as, using enzyme of Hydroxy methyl

glutaryl Co A inhibitory evaluation.


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Various Herbs Reported Active

for Lowering ChelsterolCurcuma xanthorrh iza Roxb.

The first useful anti cholesterol herb to be

discussed is Curcuma spp.

Our liver makes cholesterol as needed. If

we consume foods high in saturated fats,

the liver produces LDL cholesterol, which

is harmful to us. Curcuma rhizomes

extract works by limiting the production of

LDL cholesterol via a compound known as

curcumin, xanthorrhizol.


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Capsicum

Capsicum is a well known spicy herb

commonly used in much more than just

chili. Its stimulating properties have the

ability to increase blood flow as well assluggish circulation along with it.

Researchers have determined that this

herb has been shown to lower both highcholesterol and high blood pressure.


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Garlic

Garlic is another herb that has been used forcenturies in the treatment of many illnesses due

to its high content of sulfur compounds. It

contains roughly four times that of other

vegetables - cauliflower, onion and broccoli, alsohigh in sulfur. It keeps cholesterol levels in

balance by lowering LDL cholesterol levels, and

at the same time raising HDL cholesterol.

Garlic is a great herb. Indeed, besides being a

useful anti cholesterol herb, it has countless

other health benefits.


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Chinese Red Yeast Rice Extract

Researchers have proven that monacolin,an ingredient in red yeast rice, has the

ability to inhibit cholesterol production by

halting enzymes in the liver responsible forproducing it.

Ginger

One more of the anti cholesterol herbs isginger, which helps to raise HDL

cholesterol as well as reduce both

triglyceride and overall cholesterol levels.


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GARCINIA MANGOSTANA

-Mangostin sustains the cardiac mechanic

activities and decrease infarc area , prevent

the decrease of cardiac ATP and phospho

creatinine level in muscle cardiac

reperfusion. The xanthone protective effectis related to oxidative stress. n -Mangostin

prevents the protein oxidation induced by

reperfusion ulcer, lipid peroxidation(malondialdehyde and 4-hydroxynonenal

content)and the decrease of glutation.


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Heterobasidiomycetes (jelly

fungi) and Other Mushrooms

Auricular ia aur icula

Auricular ia po lytr icha (Hirneola

polytricha)

Tremella fuciformi

Termitomyces eurrhizus

Some of the active compounds are beta-

glucan


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O PEK BOK NIE (PREVENTING THE ARTERI

BLOCKING DUE TO CHOLESTEROL )

Auricular ia po lytr icha/Aur icular ia

auricu la (Jamur hitam putih/Jamur

Kuping) : 45 Gram

Ang Cho (Red Fruits): 10 fruitsSliced Ginger: 8 sliced (2mm thickness)

Meat (non fat): 60 Gram (optional ?)

Water : 8 Glass After washed thoroughly, boiled all

materials up 2 glasses, taken twice a

day (early in the morning and night).


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SAINTIFICATION OF JAMU FOR HEALTH CARE

RESEARCH SERVICES

Hiperglicemia

Hiper-tension

Hiperuricemia

Hipercholestrolemia

Implementation 2012

Osteo Arthritis

Anti-obesity

Anti-dispepsia

Anti-haemorrhoid

Breast Cancer

Hepatoprotector

Imunomodulator

AsmaCervical Cancer

Dermatitis alergy

Common cold

AphrodisiacAnemia

Prostate Cancer

Implementation (2013-

2014)

Implementation (2011)


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RESEARCH BASED ON DEGENERATIVE

DISEASES

Obesity

Formula based on Guazuma

ulmifoliaand Kaempferia

rotunda

Diabetes Hyper-lipidemia

Hyper

uricaemia Atherosclerosis

andcardiovascular

ArthritisImprovement for

Senility

Formula based on

Andrographis

paniculata

Formula based on Curmua

xanthorrhiza

Formula based on

Stelecocarpus

burahol

Formula based on

Artocarpus altilis

Formula based on Nicolaia

speciosa and Zingiberis

rhizomes

Formula based on Centella

asiatica

ImmuneResponse

Pandanus

conozoides


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Current Jamu Generic Preparation

Androgaphis paniculata, Tinospora crispa,Sonchus arvensis, (for Diabetes)

Caesalpinia sappan, Stelechocarpus burahol, (for

Hyperurecemia) Muraya paniculata, Guazuma ulmifolia, Curcuma

domestica, Curcuma xanthorhiza, (forHypercholesteroemia)

Apium graviolens,Orthosiphon aristatus, Centelaasiatica (for Hypertension).

The clinical observations showed that thesegeneric jamus are working well, although someimprovement are needed.


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SEARCH ON ANTICHOLESTEROL FROM

INDONESIAN FERMENTED RED YEAST

Red yeast was purchased in Serpongmarket

Solid State Fermentation resulted to the

isolation of Lovastatin/Monacolin and otherderivatives.

Further work on Anticholesterol Lovastatin

derived into Dehydrolovastatin.


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INTERACTIONLovastatin and HMG-CoA Reductase


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Interaction of Subnstrate (ball)with HMG-CoA reductase Active site

(wire string)

Interaction of Dehydrolovastatin i(grey wire string)

with HMG-CoA reductase Active site

(dark wire string)


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QSAR ANALYSIS USING HyperChem 7.0


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Treatment30 Wistar rats were divieded into 5 groups.

Group I = Normal Control

Group II = Induced High Cholestrol RatsGroup III = Simvastatin (7,2 mg/200 g bw rat)

Group IV = Dehydrolovastatin 7,2 mg/200 g bw rat)

Group V = Dehydrolovastatin 14,4 mg/200 g bw rat)

ANTICHOLESTEROL EVALUATION


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Cholesterol Total(mg/dl)

Triglyceride(mg/dl)

HDL

LDL(mg/dl)

106.29

172.53

102.28 103.85 94.79

0.00

20.00

40.00

60.00

80.00

100.00

120.00

140.00

160.00

180.00

1 2 3 4 5

Kelompok

1

1. Normal Control, 2. Cholesterol Induced, 3.Simvastatin 7,2 mg/200 gbb/day, 4.Dehidrolovastatin 7.2 mg/200 g bb/day, 5. Dehidrolovastatin14.4 mg/200 g bb/day,

ANTICHOLESTEROL EVALUATION


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Anticholesterol Evaluation Activity Results

Antikolesterol Dehydrolovastin and SimvastatinEvaluation

Parameter

Normal

Control

Hyperlipide

mia

Simvastatin

(7,2 mg/200 gbb)

Dehidrolovastatin

(7,2 mg/200 g bb)

Dehydrolovastatin

(14,4 mg/200 g bb)

Total

Cholesterol

(mg/dl)

(%)

111,7

9156,66 112,03

(28,49%)

106,64

(31,93 %)

105,54

(32,55 %)

Triglyserides

(mg/dl)

(%)

106,2

9172,53 102,28

(40,72%)

103,85

(40,0%)

94,79

(45,06%)LDL-

Cholesterol

(mg/dl)

(%)

32,34 72,99 30,23

(58,58%)

25,00

(65,75%)

28,77

(60,58%)

HDL-

Cholesterol

(mg/dl)

(%)

58,20 49,16 61,34

(24,77%)

60,87

(23,82%)

57,81

(17,60%)


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CONCLUSION

Indonesia is rich on Natural Products for the development ofnew anticholesterol active compounds.

Various studies were conducted using classicalpharmacology and biology molecular

Dehydrolovastatin showed anticholesterol activity andincreased the HDL value in rodent experiment.


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THANKYOU

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Lowering Cholesterol UPH Rev 2012