Review Article

Journal of Advances in Drug Research,Vol 1, Issue 2, June 2011 46

Review Article ISSN: 2230-7761

CASSIA AURICULATA - A PHYTOPHARMACOLOGICAL REVIEW

ABSTRACT

Ayurveda is a traditional Indian medicinal system being practiced for thousands of years. Considerableresearch on pharmacognosy, phyto-chemistrty, pharmacology and clinical therapeutics has been carriedout on ayurvedic medicinal plants. Natural products, including plants, animals and minerals have beenthe basis of treatment of human diseases. The current accepted modern medicine or allopathy has beendeveloped over the years by scientific and observational efforts of scientists. However, the basis of itsdevelopment remains rooted in traditional medicine and therapies.Cassia auriculata Linn, commonlyknown as Tanner’s cassia belongs to family Caesalpiniaceae. It is an annual or biennial shrub foundthroughout India in open forests. Traditionally it is used as anti-diuretic, astringent, anti-rheumatic,anthelmintic and antiemetic. Various scientific studies reported the Antidiabetic, Antimicrobial, Antioxidant,Anthelmintic, Anticancer, Hepatoprotective, Immunomodulatory, Antihyperlipidemic, Laxative, Anti-nociceptive and Nephroprotective properties of this plant. So, the objective of the present review is tohighlight the phytochemical and pharmacological information of this plant, which will surely aid foridentification of lead compounds from C.auriculata and further research on this plant.

KEYWORDS: Ayurveda, Astringent, Antidiabetic, Antioxidant properties, Cassia auriculata.

INTRODUCTION:

Corresponding author:

Balakrishna R.B*1, Jagir R Patel1, Prabhakaran V2

1Karavali College of Pharmacy, Mangalore, Karnataka, India.

2Krishnateja College of Pharmacy, Tirupathi, India

The origin of Ayurveda is traced back tofour books of knowledge called Vedas: Rigveda,Samaveda, Yajurveda, and Atharvanaveda. Theinformation on health care was subsequentlydeveloped by many Ayurvedic practitioners andfinally compiled into three important books known

in Ayurveda as the senior triad (vriddha traya):Charak Samhita, Sushrut Samhita, and AshtangHridaya Samhita. These books contain basicconcepts of health and disease, diseasemanagement, anatomy and physiology, hygiene,materia medica, pharmacology and therapeutics,herbal formulations, pharmacy, and synthesis ofherbo-mineral formulae.(1)

Although there is no record of pharmacologicaltesting during the time period when Ayurvedic textswere written, 50 distinct pharmacological categoriesof medicinal plants were described. Similar toconventional medicine, Ayurvedic medicine hasalso benefited from advances in science andtechnology. These advances facilitated the

R.B.Balakrishna, B.Pharm.,

Karavali College of Pharmacy,Mangalore,

Karnataka.E mail : [email protected]: +919985436410


understanding of diseases, the development ofbetter pharmaceutical products, and the impleme-ntation of diagnostic techniques. Scientific studieson laboratory animals have now confirmed thepharmacological properties of many Ayurvedicherbs.

Cassia auriculata (CA) is an annual or biennialshrub found throughout India in open forests. Theleaves are bitter, astringent, acrid, thermogenic,haematinic, constipating and expectorant; seedsare also bitter, astringent, acrid, cooling, ophtha-lmic, diuretic, alexeteric and vulnerary. The leavesare used for ulcer, leprosy and skin diseases;flowers were used in diabetes and throat troublesand the fruit is useful in vomiting. The leaf of thisplant has been used in the traditional system ofIndian medicine for the treatment of jaundice, liverdiseases, leprosy and ulcers. The powdered driedflower bud is used as a substitute for tea in thecase of diabetic patients and it is also supposed toimprove the complexion in women and alsoconsidered to be one of the important dye yieldingplants in India.(2)

Source and Botanical Description:

Botanical source: Cassia auriculata Linn.

Family : Caesalpiniaceae.

Synonym : Senna auriculata

Sanskrit Synonyms: Avartaki, Hemapushpam, Mayahari.

Regional Names: English:Tanner’s Cassia,Tanner’s Senna.

Hindi : Awal, Tarval, Tarvar.

Gujarati : Aval.

Telugu : Tangedu, Merakatangedu.

Tamil : Avarai, Avirai, Avaram, Semmalai.

Malayalam : Avara, Aviram, Ponnaviram, Jimute.

Kannada : Avarike, Ollethangadi, Taravadagida.

Shrub or small tree up to 7 m tall, with trunk up to20 cm in diameter; bark thin, brown, lenticellate.Leaves alternate, paripinnately compound; stipuleslarge and leafy, broadly reniform, 7–22 mm wide,persistent; petiole 10–14 cm long; rachis providedwith a gland between each pair of leaflets; leaflets6–13 pairs, oblong-elliptical to obovate-elliptical,10–35 mm × 5–12 mm, rounded and mucronate atapex, glabrous to pubescent. Inflorescence anaxillary raceme, 2–8-flowered. Flowers bisexual,zygomorphic, 5-merous; sepals rounded at apex;petals free, unequal, 1.5–3 cm long, yellow; stamens10, the 3 lower ones largest and fertile, othersusually sterile; ovary superior, falcate, c. 1.5 cmlong, stalked, style c. 1 cm long. Fruit a flattenedcylindrical pod 5–18 cm × 1–2 cm, transverselyundulate between the 10–20 seeds, indehiscent.Seeds compressed ovoid-cylindrical, 7–9 mm × 4–5 mm, with a distinct areole on each face.(3), (4)

Distribution

It is found in dry zones of southern, western andcentral India extending upto Rajasthan in north;also cultivated in some parts of Punjab, Haryana,Uttar pradesh and West Bengal, and often plantedin gardens for ornament and as hedges.(5)


Phytoconstituents

Stem Bark

Bark contains tannins (25 %) and ash (5%).(6) TheStem bark afforded the dimeric procyanidins,fisetinidol-(4 8”)-catechin, fisetinidol-(4 8”)-epicatechin, fisetinidol-(4 8”)-gallocatechin,fisetinidol-(4 8”)-epigallocatechin(7), rutin(5),Leucoanthocyanin -Goratensidine, characterizedas 4', 5, 7-trihydroxyflavan-3,4-diol(6) and theamorphous material extracted by acetone from barkconsisted largely of (-)-Auriculacacidin (5,2',4'-trihydroxyflavan-3,4-diol), a compound of noveltype characterized by crystalline derivatives.(8)

Heartwood

The heart wood had anthocyanin glycoside,pelargonodin-5-O- -D-galactoside.(7)

Leaves

1,3,8-trihydroxy-2-methylanthraquinone, 5-acetonyl-7-hydroxy-2-methylchromone, its C-glycoside and 5-acetonyl-7- -D-glucopyranosyloxy-2-methylchromone were isolated from leaves.(6)

Myristyl alcohol(1 g), sitosterol -D-glucoside(0.1 g), quercetin 3-O-glucoside (0.2 g), rutin (0.5g) and di-2-ethyl.-hexylphthalate (0.5 g) were alsoreported in the ethanol extract of 650 g of freshleaves.(9)

Roots

1,3-dihydroxy-2-methylanthraquinone; 1,3,8-trihydroxy-6-methoxy-2-methylanthra quinone;1,8-dihydroxy-6-methoxy-2-methyl anthra-quinone-3-O-rutinoside, 1,8-dihydroxy -2-methylanthraquinone-3-O-rutinoside(6) and a flavoneglycoside, 7', 4'-dihydroxyflavone-5-O- -D-galactopyranoside were reported in roots.(7)

Root Bark

A Chalcone 3', 6'-dihydroxy-4-methoxychalcone,two Leucoanthocyanins leucocyanidin-3-O- -L-

rhamnopyroside and leucopeonidin-3-O- -L-rhamnopyroside were isolated from root bark.(6)

Flowers

Auricassidin, kaempferol, -sitosterol12, octasonol,hentrioctanol, ceryl alcohol, peonidin-3-O- -L-rhamnopyranoside were reported to be present inflowers.(6)

Steroids, triterpenoids, lipids and flavonoids werefound to be present in the alcoholic extract of theflower while steroids and lipids were in its petroleumether fraction.(10)

Fruits

Cinnammic acid and sucrose were isolated fromfruits.(6)

Pods

Nonacosane, nonacosane-6-one, chrysophanol,emodin and rubiadin have been isolated from theshell of the pods.(5)

Seeds

Flavanol glycosides, Cassiglucin whose structurewas determined as 1,3-dihydroxy -6,8-dimethoxy-2-methylanthraquinone and Velutin-5-O- -L-rhamnopyranoside; glycosides kaempferol-3-O- -mannopyranosyl-(1 4)-O- -D-glucopyranoside,1,5-dihydroxy-4,7-dimethoxy-2-methylan-thraquinone-3-O- -L-rhamnopyranoside, 1,3,6,7,8-pentahydroxy-4-methoxy-2-methylanthraquinone,3-hydroxy-6,8-dimethoxy 2-methylanthraquinone-1-O- -D-glucopyroside, 3-hydroxy-6,8-dimethoxy-2-methylanthraquinone-1-O-rhamnopyranoside,chrysophanol and physcion were present inseeds.(6)

The total oil content in the seeds was found to be3.25%. Three sterols (cholesterol, stigmasteroland -sitosterol) and four fatty acids (palmiticacid, stearic acid, oleic acid and linoleic acid) werefound from the seed oil of both plants.(11)


The total amount of free and combined forms ofemodin, chrysophanol and physcione was foundto be 0.53% (12)

Traditional Uses

The bark is astringent and useful for gargles insore throat, in enemas, rheumatism and eyediseases. It is recommended in diabetes, and formsan ingredient in many preparations. Its decoctionis given in stomachache, and the juice of freshbark in dysentery. (13), (14)

The leaves, known as ‘Palthe senna’, are used asan adulterant of Senna; pods are also sometimessimilarly employed. A tea, known as ‘Matara” or‘Ceylon Tea’ made from the aromatic leaves driedpetals is considered refrigerant. The leaves areanthelmintic, and good for ulcers, skin diseasesand leprosy; their perfusion possesses slightpurgative property. Ground with urd and poppyseeds the leaves are applied to the herpeticeruptions. (13), (14)

The pods are anthelmintic, emetic and useful inurinary discharges. The seeds are consideredaphrodisiac, anthelmintic, alexipharmic andrefrigerant. They are used in chronic purulentopthalalmia and conjunctivitis, chyluria, gout,gonorrhea, dysentery, cough and asthma. Theyare widely used in diabetes. (13), (14)

The roots are considered astringent, cooling,depurative, alexeteric and useful in thirst,urethrorrhoea, leprosy, tumours, skin-diseases andasthma. A decoction of the roots is used as a tonic.The roots show interferon-like activity againstRanikhet Disease Virus. (13), (14)

The flowers are astringent and used in throattroubles, pharyngopathy and urethrorrhoea. Anaqueous extract of the flowers and leavespossesses hypoglycaemic activity. The flowersenter into compound syrup given for nocturnalemissions. (13), (14)

The extract of seedlings has fungistatic properties.(5) Leaves and Bark independently usually appliedon the wound for faster healing.(15), (16)

Pharmacological Activities:

Cassia auriculata has been widely screened forits various pharmacological activities. It hasrelatively well documented Antidiabetic,Antimicrobial, Antioxi-dant, Anthelmintic,Anticancer, Hepatoprotective, Immunomodulatory,Antihyperlipidemic, Laxative, Anti-nociceptive andNephroprotective properties. The various reportedpharmacological activities of Cassia auriculatahighlight the therapeutic potential of Cassiaauriculata and limitations in our knowledge asclaimed in traditional Indian medicine.

Antidiabetic activity

Leaves and flowers have promising antidiabeticactivity.(17), (18), (19) Several workers have reportedthe anti-diabetic activity of Cassia auriculata Inone study, oral administration of aqueous leafextract of Cassia auriculata. to alloxan-inducedmild diabetic (MD) and severe diabetic (SD) rabbitsproduced dose dependent fall in fasting bloodglucose up to 400 mg/kg dose from day 3 to day 21.Further, a significant elevation in the levels ofinsulin and reduction in glycosylated haemoglobin(HbA1c) was observed in both MD and SD rabbitswhen treated with 400 mg/kg dose of the extractwhich was comparable to that of glibenclamide (600µg/kg).(20), (21)

Oral administration of 0.45 g/kg body weight of theaqueous extract of the flower resulted in asignificant reduction in blood glucose and anincrease in plasma insulin.(22),( 23)

Petroleum ether and ethyl acetate extracts of Cassiaauriculata seeds, obtained by soxhlet extractionmethod showed highly significant antidiabeticactivity in alloxan (60 mg/kg through tail vein)induced hypoglycemic rats.(24)


The administration of methanolic root extract ofCassia auriculata to diabetic animals for 30 days,reverted the effects of streptozocin, and causedsignificant decrease in blood glucose (81.42%deviation when compared with blood glucoselevels) and lipid levels. Along with this, the liverglycogen level also increased significantlyindicating the sugar lowering capacity of theextract.(25)

Hydromethanolic extract along with its n-butanolfraction of Cassia auriculata flowers exhibitedsignificant reduction in blood glucose levels andwas also found effective in restoring the bloodlipids and proteins to normal levels in alloxaninduced diabetes in rats.(26)

Aqueous flower extract (CFEt) at 0.45 g/kgsignificantly decreased blood glucose,glycosylated haemoglobin and gluconeogenicenzymes and increased plasma insulin,haemoglobin and hexokinase activity, whichproved that enhanced gluconeogenesis duringdiabetes is shifted towards normal and that theextract enhances the utilization of glucose throughincreased glycolysis.(27)

The oral administration of water-soluble fractionof the ethanolic flower extract at a dose of 0.25 and0.5g/kg of body weight exhibited a significantreduction in the blood glucose level and aremarkable increase in plasma insulin level whencompared to aqueous extract-treated rats. (28)

Glucose uptake and glycogen deposition studiessuggest that Cassia auriculata aqueous leafextract probably has no direct insulin like effectwhich can enhance the peripheral utilization ofglucose.(29)

Oral treatment with the Cassia auriculata flowerextract and glibenclamide improved the erythrocytemembrane insulin binding sites with concomitantincrease of plasma insulin.(30)

Methanolic extract of dried flowers showed thestrongest AGH ( -glucosidase) inhibitory activityin vitro preferably on maltase giving an IC50 valueof 0.023 mg/mL and inhibited the maltase activitycompetitively. As a result of single oral admini-stration of methanol extract in Sprague-Dawley rats,a significant and potent lowering of blood glycemicresponse toward maltose ingestion was observedat 30 min after dosing of 5 mg/kg, thus, concurrentlysuppressed insulin activity.(31)

Cassia auriculata failed to increase glucose uptakein isolated rat hemidiaphragm in spite of apparentglucose lowering activity both in normal anddiabetic rats.(32)

The combined aqueous extracts of Cassiaauriculata and Aegle marmelos of treated animalsrevealed restoration of -cells at 450mg/body wt.(33)

The possible mechanism by which CFEt bringsabout its antihyperglycemic action may be bypotentiation of pancreatic secretion of insulinfrom -cell of islets or due to enhanced transportof blood glucose to peripheral tissue. This wasclearly evidenced by the increased level of insulinin diabetic rats treated with CFEt(23).

Antimicrobial Activity

The antibacterial property of Cassia auriculatawas reported against human pathogens by usinghexane, chloroform, ethyl acetate, acetone andmethanolic extracts. The maximum antibacterialactivity recorded in methanolic extracts againstVibrio cholorae and Staphylococcus aureus.Minimum activity was noted in chloroform extractsagainst Pseudomonas aeruginosa, no inhibitionzone present in chloroform extract against E.coli.(34), (35) Methanolic and petroleum ether extractsshowed significant antimicrobial and radicalscavenging activities and the most susceptiblemicroorganisms were found to be Pseudomonasaeruginosa and Candida albicans.(36) Methanolic


extract exhibited a higher degree of antimicrobialactivity as compared with hexane extract.(37), (38)

Maximal antibacterial activity of ethanolic,methanolic and aqueous extracts of dry flower andethanolic, methanolic and acetone extracts of freshflower was observed on Staphylococcus aureus,Enterococcus faecalis, Bacillus subtilis(39),(40),Salmonella typhi, Salmonella paratyphi A,Escherichia coli ,(39),(41), Proteus mirabilis,Pseudomonas aeruginosa using agar disc diffusionmethod(4) and cup-plate method.(42)

Aqueous leaf extract was more active than theethanol extract and Proteus vulgaris was sensitiveto ethanolic leaf extracts of Cassia auriculata.Whereas ethanolic root extract seem to be moreactive compared to aqueous extract againstBacillus subtilis(43)

Both ethanol and aqueous extracts of Cassiaauriculata leaves and barks exhibit antibacterialactivity against S.aureus and only the ethanolextracts of leaf and bark were detected againstBacillus subtilis.(44)

Antioxidant Activity

The ethanol and methanol extracts of Cassiaauriculata flowers were reported for antioxidantactivity by improved assay based on thedecolorization of the radical monocation of 2,22 -azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH)radical scavenging method.(45)

Antioxidant activity of ethyl acetate extract ofCassia auriculata leaves by using In vitro modelwas reported with the help of Nitric-oxidescavenging activity and DPPH method. Ethylacetate extract has been extremely effective inscaven-ging nitric-oxide (IC50 51.3ìg/ml). Ininhibition of DPPH Radical Scavenging activity(IC50 96.6ìg/ml) Ethyl acetate extract has showeddifferent levels of antioxidant activities.(46) Cassia

auriculata aqueous leaf extract decreased oxidativestress which might be due to its antioxidantproperties.(47)

Methanolic extract of fruits of Cassia auriculatashowed the highest antioxidant activity while themethanol extract of leaves and flowers possessedthe lowest antioxidant activity when tested for In-vitro antioxidant activity of methanolic extract ofCassia auriculata Linn. leaves, fruits and flowersusing nitric acid radical, DPPH (1,1-diphenyl-2-picrylhydrazyl) and hydrogen peroxide scavengingassay where ascorbic acid and rutin served as thestandard and positive control.(48)

Cassia auriculata flower extract and glibenclamideon antioxidants and lipid peroxidation in the brainsof streptozotocin-induced diabetic rats showedsignificant increase in the activities of superoxidedismutase, catalase, glutathione peroxidase,glutathione-S-transferase and reduced glutathione.Both the treated groups showed significantdecrease in thiobarbituric reactive substances(TBARS) and hydroperoxide formation, suggestingthier role in protection against lipid peroxidationinduced membrane damage.(49)

Cassia auriculata L. seedlings irradiated withultraviolet B (UV-B) in an environment-controlchamber and the two doses assayed (7.5 and 15.0kJ m”2) induced oxidative damage with an increasein lipid peroxidation and hydrogen peroxide and adecrease in chlorophyll and total phenol contents.The ascorbate and dehydroascorbate content aswell as the reduced glutathione/oxidized gluta-thione content and ratio significantly increased.The UV-B stress led to significant increases of theactivity of superoxide dismutase, catalase,peroxidase and polyphenol oxidase. The seedlingstried to counteract high concentrations of oxygenspecies produced under UV-B stress through a co-ordinated increase in the contents and activities ofantioxidants involved in detoxification.(50), (51)


Antihelmintic activity

The aqueous extract of Cassia auriculata leavesexhibited significant anthelmintic activity at 50mg/ml on earthworms (Eicinia faeteda), tapeworms(Raillietina spiralis) and roundworms (Ascardiagalli).(52)

Anticancer activity

Cassia auriculata leaf extract inhibited theproliferation of human breast adenocarcinoma(MCF-7) and human larynx carcinoma (Hep-2) celllines through induction of apoptosis representedby nuclear fragmentation and condensation,associated with the appearance of A0 peak in cellcycle analysis. In addition, the extract treated MCF-7 and Hep-2 cells had decreased expression of anti-apoptotic Bcl-2 protein and increased expressionof pro-apoptotic Bax protein, eventually leading adecrease in the Bcl-2/Bax ratio.(53)

The methanolic extract C.a. root showed significantconcentration-dependent inhibitory effect againstthe Acridine Orange-induced chloroplastmutagenesis of Euglena gracilis. The possiblemechanism of their antimutagenic activity couldbe the scavenging action for reactive oxygenspecies (ROS) such as singlet oxygen and/orsuperoxide anion radical as ROS play a central rolein multistage mutagenesis and carcinogenesis.(54)

Hepatoprotective activity

Cassia auriculata flowers had shownhepatoprotective activity against paracetamolinduced liver injury.(55) Microscopic examinationof alcohol-treated rat liver showed inflammatorycell infiltrates and fatty changes, which werereversed on treatment with Cassia auriculata leafextract.(53) The hepatoprotection offered by the leafextract were mediated probably due to theprotection against free radical mediated oxidativestress in experimental hepatotoxicity.(56)

Immunomodulatory activity

Methanolic extract of Cassia auriculata tested bythe humoral (antibody titre) and cellular (foot padswelling) immune responses to the antigenicchallenge by sheep RBCs and by neutrophiladhesion test, showed that it significantlystimulated the cell mediated immunity by facilitatingthe foot pad thickness responses to the sheepRBCs in sensitized rats.(57)

Antihyperlipidaemic activity

The antihyperlipidaemic effect of CFEt may be dueto the down regulation of NADPH and NADH, acofactor in the fat metabolism. Higher activity ofglucose-6-phosphatase provides H+ which bindswith NADP+ in the form of NADPH and is helpfulin the synthesis of fats from carbohydrates. Whenglycolysis slows down because of cellular activity,the pentose phosphate pathway still remain activein liver to breakdown glucose that continuouslyprovides NADPH which converts acetyl radicalsinto long fatty acid chains. CFEt may be capable ofoxidising NADPH. Enhanced hexokinase activityin CFEt treated rats suggests greater uptake ofglucose from blood by the liver cells. (23)

Activities of enzymes suggest that enhanced lipidmetabolism during diabetes is shifted towardscarbohydrate metabolism and it enhances theutilisation of glucose at the peripheral sites. Oneof the possible actions of CFEt may be due to itsinhibition of endogenous synthesis of lipids. (23)

CFEt may antagonise the metabolic aberration andthereby restore the normal metabolism by tiltingthe balance from high lipids to high carbohydrateturnover. Alteration of fatty acid composition byincreased lipid levels contribute to lowering theresistance of tissues and higher rate of oxidativestress. Decreased activity of glucose-6-phosphatase through pentose phosphate shuntresults in high reduced glutathione to oxidized


glutathione ratio (GSH/GSSG), which is coupledwith conversion of NADPH to NADP. CFEt mayproduce high NADP+ which results in downregulation of lipogenesis and lower risk of thetissues for oxidative stress and high resistance fordiabetes. (23)

Treatment with Cassia auriculata leaf extract hasa lipid-lowering effect in rats with experimentallyinduced, alcohol-related liver damage. This isassociated with a reversal of steatosis in the liverand of spongiosis in the brain.(58)

The levels of serum TC, TG, LDL, and VLDL werereduced significantly, where as HDL levels wereincreased in animals fed with aqueous extract offlowers of Cassia auriculata on streptozotocin(STZ) induced diabetic rats.(59)

Laxative Activity

The methanolic extract from the flowers of Cassiaauriculata showed a significant and dose-dependent laxative activity, as indicated byincreased faecal output in rats. Such laxativeactivity was comparable to that of the standard.The laxative activity of Cassia auriculata wasattributed to the presence of anthracene derivativesin its flowers.(60) Ethanol extract of pods was alsoreported to have laxative activity in rats.(61)

Anti-nociceptive activity

The aqueous extract of Cassia auriculatapossessed anti-nociceptive activity in mice at thedoses of 150, 300, 500, mg/kg.(62)

Nephroprotective Activity

In the cisplatin model, the ethanol extract of theroots at doses of 300 and 600 mg/kg body wt. inmale albino rats, reduced elevated blood urea andserum creatinine and normalized the histopa-thological changes in the curative regimen. In thegentamicin model, the ethanol extract at a dose of

600 mg/kg body wt. reduced blood urea and serumcreatinine effectively in both the curative and thepreventive regimen. The extract had a marked nitricoxide free-radical-scavenging effect. The probablemechanism of nephroprotection by Cassiaauriculata against cisplatin- and gentamicin-induced renal injury could be due to its antioxidantand free-radical-scavenging property.(63)

CONCLUSION

In the present review we have made an attempt tocongregate the botanical, phytochemical, pharma-cological and ethno pharmacological informationon Cassia auriculata. This information will surelyhelp researchers/Investigators to carry out furtherwork on Cassia auriculata , which may help inidentifying lead compounds or developing suitableformulations.

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