Journal or Scientific & Industri al Research Yol.60, January 200 I, j:Jp 1-9

Chemistry and Pharmacology of Rhubarb (Rheum species)- A Review Santosh K Agarwal *, Sudhir S Singh, Vijai Lakshmi+,

Sushma Verma and Sushi! Kumar Central Institute of Medicinal and Aromatic Plants (('SIR) , Lucknow 226 015 , India

+Central Drug Research Institute (CSIR), Luck now 226 00 I , India

Various chemica l constituents iso lated from rhubarb (Rheum ) species include anthraquinones, di anthrones, stilbencs. anthocyanins, navonoids, anthragl ycos icles , polyphenols , organic acids, essential oi ls, vitamins, chromenes, chromanone and chromone glycosides . Notable biological ac ti viti es reported rro111 ,, ,l. vari ous parts or the plant and its iso lates arc cath arti c. an tibacteri al, fatal poisOfling, antiviral, anti inllammatory, mollusciudal , anticoagulant , spas molyti c, cytotoxicity. chronic rcn;ll failure, chemiluminescence quencing and an ti -p latelet acti vities.

Introduction Rheum Linn (family polygonaceae; English name:

rhubarb), a large genu s of perennia l, stout he rbs and dis-tributed in the temperate and sub-tropical regions of the world, chiefly in Asian countries, viz. India (Kashmir, Assam, Sikkim), Nepal , Bhutan, China, Pak istan , Ko-rea, Turkey, Russ ia and Tibe t. Several species of this plant are used in medicine, some for culinary purposes and few others are grown as ornamental plants. There are three main types of rhubarb , viz. the Chinese Rhu-barb, the Indian or Himalayan Rhubarb and the Rhapontic Rhubarb u. Some known s peci es of Rh eum are R. acuminatum (R-1 ), R. alexandrae (R-2), R. altai cum (R-3), R. australe (R-4), R. compactum (R-5), R. coreanum (R-6), R.corodatum (R-7), R. delavayi (R-8), R. emodi (R-9), R. franzenbachii (R- 1 0), R. hotaoense (R-11 ), R. hybridium (R-1 2), R. kialense (R-1 3), R. /hasa ense (R-14), R. maximoviczii (R-15 ), R. moorcro.fiianum (R-16), R. nobile (R-17), /?. offlcina /e (R-1 8), /?. pa/aestinwn (R-19), R. palmatum (R-20), /?. pami/um (R-2 1 ), /?. ribes (R-22), /?. rhabarbamm (R-23), R. rhaponricwn (R-24), (R-13), R. lhasaense (R-14 ), R. maximoviczii (R- 15), /( moorcrojtianum (R- 16), /?. nobile (R- 17), /?. oJficina /e (R-1 8), R. palaestinum (R- 19), R. pa/matuiii (R-20), /?. pamilwn (R-21 ), R. ribes (R-22) , R. rhabarbarwn (R-23), R. rhaponticum (R-24), R. spiciforme (R-25), R. tanguticum (R-26), R. tataricum (R-27), R. undu/atum

*Author for correspondence CIMAP Publi cat ion No.: 99-11 R

(R-28) , R. webbianum (R-29), /?. willrockii (R-30) and R. qinlingense (R-31 ). About ten spec ies are found in India.

Indian rhubarb , which is offic ial in Indian Phar-macopoeia, consists of the dried rhizomes of R. enwdi and R. webbian um and other species of Rheum. Rhi zomes and roots of R. moorcroftianum and R. spicifonne are also reported to be mixed with the drug. The plant grows wild at an altitude of about 4000 to 12000 feet. Rhubarb has been successfully grown in certa in parts of Assam also. Indian rhubarb occurs in sub-cy lindrica l or irregu-lar pieces, ranging from 2 to 20 em in length and 1.5 to 2.0 em in diameter, much shrunken, lig ht in we ight. It is some what dark in colour, almost odourl ess or some-what fragrant with a bitte r and astringe nt taste. It con-tains anthraquinone derivatives and y ie lds about 25-30 per cent o f ~x trac t solubl e in 50 pe r cent aqueous alco-ho l' . In ayurvedic preparations, rhubarb has long been used as an ingredient of purgatives, laxatives and sto-

machic-tonics ' ~. It is hoped that the rev iew would be useful to those work ing in the fi e ld of phytochem ica l invest igations of rhubarb.

Chemistry A varie ty of const ituents have been iso lated fro m

Rheum spec ies and the ir structures e luc idated. They be-long to such classes as anthraquin ones, clianthroncs, stil-benes, anthocynin s, rla vo no icl s, an thrag lycosid es, polyphenols, essenti a l oi l. o rganic ac id s, chromcnc,

2 J SCI IND RES VOL.60 JANUA RY 2001

chromanone, chromone glycos ides and vitamins. Analy-sis of samples of the rhubarb contained (in percent ) ash, 9.3-4.9; protein , 1. 1; fibre, 1.3-0.8; catharti c acid , 3.5-3.2; organi c ac ids, 3.3-2.2 ; and sugar, 1.4- l . l ; respec-tively' .

Essential Oil.\ The essential oil s (0.05 per cent) obtained fro m

rhi zomes of R. cmodi have charac teri stic odour due to the presence of eugenol and meth yl heptyl k eton e~ . The vo latile oil from rhi zomes of R. polnw lun1 contained I 08 vola til e components of which 27.3 per cent were terpe-noid s. The main constituent s were (per cen t): palmitic aciu (22. 5) , paeono l ( 16. 2), a -co paene (9.8), met hyl stea rate (9.3), 8-cadinene (5.4), and methyl-eugenol (5.4)('. An 1 h raquinones

Many an thraq uinones have been iso lated from dif-ferent spec ies of rhu barb. A few of them are physcion , ch rysophanol (c hrysophanic acid or chrysophan) , rhein , emodi n, aloe-emodi n, rh e inal , hydroxy-meth yl an -th raq uinone and Jst izin. Out of these anthraqu inone de-rivatives, most of the rhubarb spec it.:s contain 7 physc ion, chry~oph anol, emodi n, al oe-emodin and rhein as shown in Tab le I. Indian rhubarb (R. cmodi) was found to con-tain free rhein (0.48) , free chrysophanol (0.50) and gly-cosidic rhein ( 1.52) and glycos idic chrysophanol (0.4 1 per cen t)1. The antimicrobial acti vity of rhein was al so observed aga inst Escherichia coli, Bacillus suht iles, Micrococcus luleus, Candida albicons. Clost rirliulil pe1ji-ingr'il.\' and Fusofacleriu/11 voriwn 1. We have also isolated a new anthraq uinone deri vative rheinal (0.008 p,cr cent) from the rh izomes of R. cnwdi ~. Dianthrones

Rheidin A is a heterodianthrone co mposed of one mole of emodin and one mole of rhein anthrone, obtai ned from 1

AGGARWAL eta/.: CHEM ISTRY & PH ARMACOLOGY OF RH UBARB 3

Chromene, Chrornanone, and Chromone Six chromone and chromanone deri vatives211 have

been isolated from rhubarb together with two chromone g lucos ides 211 Th ese are : 2,5-dimeth y l- 7- hyd roxy-chromene; 2-methyl-5-acetyl-7-hydroxy-chromene; 2-methyl-5-carboxy-methyl- 7 -hydrox y-chromenc; 2-(2'-hydroxy l-propy 1-5-methy 1-7 -hydroxychromene; 2- me-thyl-5-carbox-ymethyl-7-hyd roxy chromanone; Aloe-

sone-7-0- ~-D-gluco-pyranos ide and 2-methyl-5-(2'-oxo-4'-hydroxypentyl)-7-hydroxy c hromone-7-0 - ~ -Dglucopyranos ide.

Polyphenols A large number of polyphenols isolated from dif-

ferent spec ies of rhubarb include: (-)-epi gallocatechol, ( + )-ga ll ocatec hol, (- )-epigallocatec hol-gall ocatec hol, ( + )-gall ocatec hol ga ll ate, (+)-catechol, (-)epicatechol gallate, catechins, (-)-epicatechol, (- )-epicatechin ga llate, ga llic acid, glucoga llin, kaempferol, 4,8'-bis-3-0-galloyl-(-)-epicatechin , 4' ,8-3-0-galloy 1-(-)-epicatechin-( +)-cat-ec hin , d-catec hin , pyroga ll o l, ca rvacro l and 4-methoxyga llic ac id . The ast rin gent principle consists chiefl y of ga llic ac id , present as gl ucoga ll in , together with small amount of tannin and poss ibl y catec hin . Glucoga llin on hydrolysis yielded galli c acid and glu-cose1.

Anthraglycosides Anthraglycos ides are found almost in all the spe-

cies of rhubarb and a few of them were: rheochrys in , aloe-emod i n-8-0-~-D-g l ucos ide, emod i n-6-0-~-D-g l uco-side, rhe in- 8-0-~-D-g lucos i de, rheinos ide A, rheinos ide B, rhein os ide C and rhe in os ide D, sennos ide A and senn os ide B, to rachryso ne- 8-0-~-D-glucopy ra n os id e, kaempfe ro 1- 3-0-a- L-rh amn os id e, chryo- phan e i n, chrysop han ol-8-0- ~-D-gl ucos ide, emod in -8-0- ~-D-gluco-pyranos ide, chrysophano i - 1 -0- ~-D-g lucos id e and

rh e in-II -O-~-D-g lucos id e2 (Ta ble I). Pharmacology

Rhubarb is large ly used as purgative in wes tern medicine. It is a good laxative, stomac hic, bitter, tonic and ca tharti c, so it is well fitted for use in simpl e diar-rhoea2 It is so safe that it cou ld be given to children as well as old peop le. Its use is prohibited for pati ent s suf-fering from gou t, rheumati sm, ep il epsy and uri c acid . troubles. Powdered roots arc used fo r cleaning tee th and are also sp rinkled over ul cers for quick healin g.

The drug is used in Ayurveda. ln th e Unan i sys-tem, it is a constituents of " [tri fa l Mulayy in", used in ordinary constipati on and other di gesti ve disorders, ''Hab Shabyar" where headache of different intensity are con-sidered clue to a disturbance in the di ges ti ve system, "Haba Shafa", for an obstin ate type of cough and cold and of "Roughan Aq rab", applied on pil es because or the astringent action of Rheum. "Qur Didan" is an an-thelmintic' .

Rhubarb forms an important ingredi ent of a \'a ri-ety of medicines. It is an exce ll ent remedy for irrit ation of the bowels, common among child ren durin g teething and in chronic dysentry, du odenal catarrh or catarrh of the biliary ducts with jaundice and in certain sk in dis-eases2. Fres h rhubarb juice showed anti scorbuti c act iv-ity3

The plant also possesses antibiotic propcrti es 13 It is used as an antibacteri al aga inst Stapltvlococcus mm' us, Escherichia coli or Brucella obortu.1~ . Rhubarb extract had a laxative effect due to its content of hyd roxy me-thyl anthraquinone and tannins-' . It also has cathartic ef-fect357 Cooked leaf and stems are harm less in moderate quantities but the leaves may cause fa tal poisonin g~.

Rhubarb is used as an antiviral agent against Vori-cello zoster virus and He1pe.1 simplex virtt.\Tubello'x . The minimal inhibiti ve closes aga inst Voricc llo z.osrer and HcrJ"Jes simf'J iex vimsrubello G and JR ,

1 were I 00-

11\ J() - -5000 mg/L. It has also shown antiinflammatory act i v-ityl . Anthraquinones of rhubarb had mollusc icidal ac-ti vit y against the schi stosome vector snail s On colllclu-nio , Biomphalaria and Bulinw5~. Chrysophanic acid and cl -catechin obtained from rhubarb had shown prolonga-ti on of prothrombin time which is a measure of coagu-i

4 J SCI IND RES VOL.60 JANUARY 2001

Table I - List or compou nds iso lated from illerent spec ies or rhubarb

Sl. No. Name of compound

Essential Oils

Eugenol, bp, 255"

2 Meth yl hep tyl ketone

3 Paeonol

4 a -Co paene. bp, 246-25 1"

5 6

7

(aj 0 - 6.3" (c= 1.2 in C HC I1). Methyl stearate

P-Cadi nene

[a]o-25 1" Meth yl-eugenol

Anthraquinones

8

9

10

II

12

13

14

15

Physc ion, mp. 2 10"

Chrysophanol or Chrysophan

Chrysophanic ac id , mp, 196"

Aloe-emodin, mp. 223 -224"

Emodin, mp. 256-257"

Hydroxy-methyl anthraqui none

mp, 302"

Rhein, mp, 32 1-322"

Rheinal, mp, 236-238"

Isti zin

Dian thrones

16

17

18

19

Organi

20

2 1

22

Rheidin A

Sennidin C

Rheidin B

Rheidin C

Acids

Oxa lic acid, mp, 101 - 102"

Palmitic acid, mp, 63-64"

Aceti c acid , bp, 11 8"

Name or plant

R-9

R-9

R-20

R-20

R-20

R-20

R-20

Rhubarb, R-9 , R-20. R- 18,

R-26. R- 10. R-22. R- 16. R-31

Rhubarb, R-9, R-20. R- 18.

R-26. R-10. R-22, R- 16.

R-24. R-27

Rhubarb, R-9, R-20. R- 18.

R-26, R-1 0, R-6

Rhubarb, R-9. R-20, R- 18,

R-26, R- 10, R 24, R- 16. R-27

Rhubarb ,

Rhubarb, R-9, R-20. R- 18.

R-26. R- 1 0. R-22. R-24

R-9

Rhu barb

R-20

Rhubarb

Rhubarb

Rhubarb

Rhu barb

Rhubarb

Re ference~

4

4

6

6

6

6

6

2 1-29

I . 2 1-31

4, 2 1-23. 25-28, 32

4. 2 1-23. 25-3 1

4

1-4.2 1-24.26-28 .

30

2 I , 33

3, 8

3.9

3, 9

3,9

4.5

R-20. R-26

5, 10

- Contd.

AGGARWAL eta /.: C HEMISTRY & PHARMACOLOGY OF RH UBARB

Table I - Li st of compounds isolated from different species of rhubarb - Contd.

23

24

25

26

27

28

Stilbenes

29

30

3 1

32

33

34

35

36

37

38

Succinic ac id , mp, 185- 187"

Lac ti c acid, mp , 53"

[a] 0 - 2.6" Malic acid, mp , 13 1-1 32"

Citric ac id , mp , !53"

Fumaric acid, mp , 230"

Formic ac id , bp , I 00.5''

Rh aponti cin or Rhapontin

mp, 236-237"dcc

[a] 0 - 59.5" (Acetone) Deoxyrh aponticin

Rhaponti cin-~-D-g lucoside mp, 230-231 "

Desoxyrh apontigenin

Rhapont igenin, mp , 185"

Piceatanno l, mp , 23 1-232"

4'-0-Methylpiccid

Piceatanno i-4'-0-

-~ -D-glucopyranoside

Rhaponti genin -3'-0-

-~-D-glucopyranoside Piceatannol-3'-0-~-Dg lucopyranos ide (Rheumin )

Flavonoids

39 Quercetin, mp, 3 14" dec 40 lsoquercetin , mp, 225-227"

41 Meratin, mp, 180"

42 Rutin , mp, 2 14-2 15" dec

[a] 0 + 13.82" (Ethanol) 43 Quercetin -3,7- glu coarbi nos ides

Anthocyanins

44 Cyanidin-3-g lucoside mp, 205" dec

Rhubarb

Rhubarb

Rhubarb , R-1 2

Rhubarb

Rhubarb

Rhubarb

Rhubarb , R-22, R-24,

R-20, R- 18, R- 11

R-24, R-30

R-9, R-20, R-24

R-28

R-28 , R-1 I

R-2 8, R-30

R-20

R-30

R-28

R-28

R-27, R- 30

R-27, R-30

R-27

Rhubarb, R-27, R-30,

R-30

Rhubarb , R-24

5, 10 5, 10

5, 10 5, 10

10

10

24, 34-37

34,38,39

4,40, 41

42 , 43

2!i , 37 , 42 , 43

28 , 39, 42 , 43

41

39

44

37 , 44

12, 13

12, 13

12

12- 14

!3

15-17

- Contcl.

5

6 J SCI IND RES VOL.60 JANUA RY 2001

Table I - Li st or compounds isol

AGGARWAL eta/.: C HEMISTRY & PHARMACOLOGY OF RHUBARB

Tabl e I - Li st of compounds iso lated from different spec ies or rhubarb - Contd.

68

69

70

71

72

Gallic acid, mp. 235-240"

Glucogall in

Kaempfcro l , mp. 276-278"

4.8'-bi s-3 -0-Ga ll oyl-(- )-epica techi n 4 .8'-3-0 -Gall oyl-(- )-ep ica techi n -(+)-catechin

73 Pyroga ll o l, mp. 13 1- 1 3:1''

74

75

Carvacrol , bp. 11 8- 122"

4-Methoxygallic acid

Ant hraglycosides

76

77

78

79

84

85

8(i

87

88

Rheochrys in

Aloe-emodi n-8-0-~-D-gl ucosid

8 J SCI IND RES VOL.60 JANUARY 200 1

Table I - Li st o f compounds iso lated from different species or rhubarb - Contd

90 A l oe-cmod in - 1 -0-~- - D-gluco pyra n oside

91 Torachryso ne-8-0-~--D-g lucopyranosidc

92 K aempferol-3-0-a-L-rhamnosidc

93 Ch rysophanein. mp. 246"

94 Ch rysoph a no i-8-0-~-D-g lu cosi d c mp, 245-246"

95 Emod i n -8-0-~-D-glucopy ra nnsi de mp, 2 10-2 11 "

96 Chrysoph a n oi-1-0-~- D-g l ucos i dc mp. 248-249"

97 Chrysoph a no i-8-0-~-D--(6 '-malonyl)-g lucopyranosidc

98 Physcion-8-0-~-D-glu cosidc

in loweri ng serum cholesterol concentrati ons, especially LDL cholesterol, in hypercholesterolemic men1''.

Conclusion Rhubarb possesses wide range of biolog ica l activ i-

ties and have revealed compounds of many chemi cal classes . Ninety eight compounds iso lated from these species include five flavon oids , twelve anthraquinones, ten stilbenes, sixteen polyphenols and twenty-t hree anthrag lycos ides and rest others. It is believed that thi s rev iew would be of immense use for researchers work-in g in the fi eld of phytochemica l in vest igat ions.

References Ahmad Z, Jafri M A & Javed K , Indian Dmgs. ]5 ( 1998) 75-78.

2 Aganv:JI S K , Singh S S, Verma S & Kum;lr S. Inc/ion .I Chen1 , 3813 ( 1999) 749-75 1.

3 Thakur R S, Puri H S & Hussain A, Major Medicinal Plants oj' India , ( 1989) 443-447.

R-28 56

Rhubarb, R-28 20

Rhubarb 20

R-20 4

R-28. R- 3 1 44. 56

R-28. R-3 1 44.56

Rhu ba rb 4 1

R- 3 1 56

R-3 1 56

4 Chopra R N, ayyar, Chopra, Clos.wrr o( Indian Medicinal Plan is ( 1978) 212.

5 Yosu hi ko M , NiJIJIOII S/wkuhin Kug\'o Cakkaish i, J I ( 1964) 444-46: Chon Ah.11r, 64 ( 1966) 1269a.

6 Mi yazawa M , Minami no Y & Kameoka 1-1 . Flavour Fmgro11n ./, II ( 1996) 58-60.

7 Xiao P G, Chen B Z. Wang L W, Hn L Y & Lun SR. Guo Hang Zhou Yao 1-/sueh 1-/sueh Pao , 15 ( 1980) 3J-39: Che111 Ahsir. 93 ( 1980) 2453301'

8 Lern li J. Dequckcr R & Cuvcc lc J. Plwnn \Veekblad, X9 (I %3) 655-659; Che111 Ahsir. 60 ( I %4) 365g.

9 Lernl i J, Dequckcr R & Cuvcclc J. Phwm \Veekhlwl. 99 ( 1964)613-616:Che111Ah.l'll'. 61 (1964) 13 125c.

10 Blundstone H AW & Dickin son D . ./ SCI Food Agric. 15 ( 1%4) 94- 10 I : Chen1 Ahslr. 60 ( 1964) 1357011.

II Wang X , Zheng J & Chen Q, Zhong~uo )l:w.rue Za::.hi. 30 (I t)f.J5) 7 19-20; Che111 Ahsir 124 ( 14) ( 19%) 18575 1 r.

12 Chumha lov V T K & Nurgalieva G M, Kh i111 Prir Srwdin. 3 ( 1% 7) 345 -346: Che111 A IJs lr , 6X ( 196X) 275 16p.

13 A lyukina L S. BaigoLina V P & Rama7.anova Zh Tr. Ins/ /Joi Akad Nauk Ku;. SSt?. 28 ( 1970) 170-178: Che111 Ahstr, 73 ( 1970) 127773s.

AGGARWAL et a/. : C HEM ISTRY & PHARMACOLOGY OF RHUBARB 9

14 Horhammer L & Muller K , Arch Phar111 , 2X ( 195-+) 126: Ch('/11 AIJSfl, 49 ( 1955) 5701.

IS Wrol stad R E & Struthers B J, .I Chm111 , 55 ( 1971 ) 405--+0~. 16 Wro lstad R E & Heathcrbcll D A , J Food Sci , 33 ( I % ll) 592-

594. 17 Hctmanski W. Nvbo111 Nils Fmchtsafi l11d. 12 ( 190!\) 256-260:

C/ret/1 Ahstr, 71 ( 1969) 29360u. I S Nurgal icva G M & Chumbalov T K , Feno/inyo Soedin 1/.:h /Jiol

F11n/.:ts Mat er Vses Si111p !st. ( 1966) 93-95: Client Ahstr. 71 ( 1969) I 0257u.

19 Alli son R M , .I Sri Food Agric, 17 ( 1966) 554-557. 20 Kashiwada Y, Nonaka Gcrminacol & Nishioka I , fJhwochelllis -

try, 29 ( 1990) I 007-1009. 2 1 Wang Z, Hong X & Li Z, Zhrmggrw Zl11mgrao Za:hi. I X ( 1993)

488-491; Che111 Abstr, 120 ( 1994) 27479w. 22 StahlE & Mcnsscn H G, Otsch Apoth Ztg, 125 ( 19X5) 1-+ni-

1480; Che11t Abstr, 103 ( 1985) 109832u. 23 Ma X, Chen Y & Hui R, Chronrwogmphia , 27 ( 19X