Gupta Sudesh et al. IRJP 2012, 3 (12) INTERNATIONAL RESEARCH JOURNAL OF PHARMACY www.irjponline.com ISSN 2230 – 8407 Review Article

ETHNOPHARMACOLOGICAL POTENTIAL OF PROCERA: AN OVERVIEW Gupta Sudesh1*, Gupta Bhawana2, Kapoor Karishma1, Sharma pooja1 1Department of PG studies in Shalyatantra, Jammu Institute of Ayurveda and Research, Nardini( Raipur), Bantalab Jammu, J&K, India 2Medical officer, National Rural Health Mission, Ministry of Health and Family Welfare, Govt of India, PHC-Siot, District- Rajouri, J&K, India

Article Received on: 07/10/12 Revised on: 11/11/12 Approved for publication: 02/12/12

*Email: [email protected]

ABSTRACT The herbal medicine occupy distinct position right from ancient period. The Calotropis procera is known by different names in different part of the world. It is a wild growing medicinal plant distributed throughout India. The various parts of the plant are practiced in various traditional systems of medicine around the world and popular among the various ethnic groups for the treatment of variety of ailments. Following the various traditional claims on use of Calotropis procera in curing number of diseases, considerable efforts have been made by researchers to verify its utility through scientific pharmacological screenings. Pharmacological studies have revealed that aqueous and organic extracts of various parts of Calotropis procera and its constituents possess a wide range of biological activities such as antidiabetic, analgesic, anti-inflammatory, antiarthritic, antioxidant, anthelmintic, anticandidial, wound healing, anticonvulsant, antitumour, antiasthmatic, hepatoprotective and cytotoxic. The studies have also revealed the toxic effects of the plant in some experimental animal models on chronic use. This review presents a detailed survey of the literatures on traditional, pharmacognostical, phytochemical and experimentally evaluated medicinal uses of Calotropis procera. Keywords: Calotropis procera, Medicinal , Ayurvedic medicine, Pharmacological studies, Toxic effects

INTRODUCTION highlight the various traditional, folkloric uses, Calotropis procera is a genus of about six species of shrubs pharmacognostical, phytochemical and pharmacological or small trees, distributed in tropical and subtropical Africa investigations carried out over years, to explain the and Asia. Among these three species found in India and two multifaceted role of this medicinal plant. of them, C.procera and C.gigantia are of economic and medicinal importance. The generic name Calotropis is taken Table 1: Vernacular Names of Calotropis Procera Languages Vernacular Names from kalos (~beautiful) and Tropis (~a keel), alluding to the Sanskrit Shweta arka, Ravi, Arka good look of the keel of flower. Calotropis procera of family English Madar tree Asclepiadaceae is a tropical plant growing wild in warm Hindi Aak, Akavana, Madar climate upto an altitude of about 1050 meters. The plant is Marathi Rui, Mandara Gujarati Akado distributed throughout india particularly abduntant in Punjabi Ak Rajasthan. It also occurs in Pakistan, Africa, Mexico, Kannada Ekka, Ekkadagida Australia, Egypt, Central and South America and Caribbean Telgu Jilledu island1. The Plant is a small shrub covered with cottony Tamil Vellerukku Urdu Madar, Aak tomentum. The bark is soft, corky and light grey. The leaves Oria Arakha are opposite, sessible, oblong-obovate, short pointed to blunt Kashmiri Acka at the apex and are about 7 to 18cm long and 5 to 13cm Bengali Akanda, Akone broad, slightly leathery and have a fine coat of soft hair. The Assami Akand, Akan flowers are white to pink or spotted purple. The fruit are Malyalam Erikku inflated, 8-12cm long, grey-green in colour and release flat, Medicinal Uses: In Traditional Medicine brown seeds with a tuft of white hair at one end. The roots The plant has been widely used in the Ayurvedic, Unani, are simple, whitish-grey in colour with wrinkles, curved Arabic and Sudanese-Indian traditional system of medicine woody appearance and exhibit marks of sap exudation on the for the treatment of various ailments. It has been used as a surface. The root is bitter in taste and has no specific odour. purgative, anthelmintic, digestive, stomachic, emetic, The aerial parts of the plant contain milky sap called latex 2 expectorant, sedative, blood purifier, an antidote for snake present in the lactiferous channels . Calotropis procera is poisoning and for the treatment of ulcers, tumors, leprosy, known by various names like apple, Sodom apple, asthma, boils, dysentery, eczema, piles and diseases of liver, Swallow wort, and Milkweed. In India, the plant is known by abdomen and spleen3. various vernacular names. Ethnobotanical Uses The various parts of the plant viz., flowers, stem, leaves, Almost all the parts of C.procera have been documented to roots and the milky latex are practiced in various indigenous possess medicinal virtues in ethnobotanical surveys systems of medicine around the world and popular among the conducted by researchers in India. The kol tribes of Banda various ethnic groups in India for the treatment of variety of district, Uttar Pradesh are using leaves for the cure of cold, ailments. Following a large number of claims on the wide cough and latex for toothache and scorpion bite4. The tribals range of folk medicinal properties of C.procera, considerable of sagar district of Madhya Pradesh using latex of the plant efforts have been made by the researchers to justify its for the treatment of dropsy, rheumatism, leprosy and taeniasis efficacy as a curative agent through pharmacological while roots for elephantiasis5. Taxo-ethnobotanical studies of investigations. The objectives of present review is to rural areas in rajouri district of Jammu have reported that the Page 19 Gupta Sudesh et al. IRJP 2012, 3 (12) native villagers are using latex for application on wounds and Root: Transverse section of matured root shows three to eight as a masticatory6. layers of tangentially elongated and compressed cells with In other surveys, latex has been described to possess suberised wall composing phellem. The phellem is followed abortifaciets7, antiseptic8 and laxative properties9. The roots by phellongen which is distinct and consists two to three of the plant reported to be beneficial in cough, asthma10, layers of tangentially elongated cells. Phelloderm is fever and swellings11; while flowers for the treatment of composed of large polyhedral tangentially elongated cells. cholera12 and stomach disorders13. Some of the cells possess prismatic and rosette crystals of calcium oxalate and contain starch grains. The secondary phloem which occupies a broad zone consists of sieve tubes, companion cells, numerous phloem, parenchymatous cells and is transverse by uni to tetraseriate medullary rays. The phloem is followed by cambium in the form of narrow strip containing two to five rows of thin walled tangentially elongated cells. Secondary xylem occupied central portion of root and consists vessels, tracheids, fibers and xylem parenchyma20. Chemical Constituents The entire plant has been reported to contain alkaloids, sterols, flavonoids, cardiac glycosides, triterpenoids and usharin21. The root bark was found to contain In Ayurveda benzoyllineolone, benzoylisolineolone, calotropterpenyl The plant is attributed medicinal in number of classical texts ester, calotropursenyl acetate and calotropfriedelenyl acetate. of Ayurveda like Ashtang Hridays, Bhavprakash Nigantu, The root and root bark also reported to contain α-amyrin, β- Dhanvantri Nigantu, Raj Nigantu, Shaligram Nigantu, amyrin, taraxasterol and its four J-isomer, taraxasteryl 14,15 Sushruta Samhita, etc . It is reported to have tikta rasa, isovalerate, taraxasteryl acetate, β-sitosterol and quercetin-3- laghu guna, ushna virya and katu vipaka. It is mentioned as rutinoside22. The latex of C.procera has been analysed by bitter tonic, laxative, anthelmintic, expectorant and to cure various workers for their chemical constituents. The latex is ulcers. The leaves are applied hot to the abdomen to relieve acidic in nature, with specific gravity of 1.021 and contains the pain inside. The flowers are described as tonic, appetizer, 14.8% solids. A nontoxic proteolytic ezyme, (2- stomachie, antisialagogue, to cure piles and asthma16. The 3%) and a powerful bacteriolytic agent capable of lysing roots of the plant are reputed to be useful and utilized in Micrococcus lysodeikticus have been isolated from the preparation of Dhanvantri Ghrita, Chitrakadi taila, latex23. Prabhanjana Vimardana taila, Mahanarayan taila, Various cardiac glycosides viz., calotropin, calactin, Saindhavadi taila, Arka lavana, Abhaya lavana, Vajraka calotoxin, usharin, usharidin and voruscharin are found to kshara, Ekangveera rasa, Bhrihat Kasturibhairva rasa, contain in the latex of the plant24. Latex also reported to Vatavidhavamsana rasa, etc. All these are classical Ayurvedic contain proteases calotropin DI and DII and calotropin FI and 17 preparations . FII, an enzyme with invertase activity and trypsin. Non- Therapeutic Utilities Atriterpene characterized as taraxast-20(30)-en-3(4-methyl-3- Latex obtained from the plant is used to a limited extent in pentenoate) has been isolated from the latex25. Mudarine has the tanning industry for the purpose of deodorizing, removing been isolated as the principal active constituent from the hairs and imparting a yellow color to the hides. Stem of the leaves of plant. The leaves and stalk found to contain plant yields fibers, which are used in rural parts of India for calotropin, calotropagenin, cardenolides, stigmasterol, β- making fishing nets and lines, bowstrings and twine. The sitosterol, quercetin-3-rutinoside and triterpenoids26. floss, being short stapled, by admixing with cotton used for Procesterol, a new steroidal hdroxy ketone, has been isolated 18 stuffing mattresses and pillows . from the fresh and undried flowers of C.procera27. Pharmacognostical Studies Pharmacological Activities Leaf: Transverse section through midrib shows an upper and Antidiabetic Activity lower single layered epidermis externally covered with thick, Dry latex of C.procera was evaluated for its antioxidant and striated cuticle, few epidermal cells on both surfaces of leaf anti-hyperglycemic effects against alloxan-induced diabetes elongated to form uni-seriate, 2-3 celled trichomes, epidermal in rats. Daily oral administration of dry latex at 100 and cells cubical and radially elongated, epidermis followed by 3- 400mg/kg doses produced a dose dependent decrease in the 8 layered collenchymas on both lower and upper surfaces, blood glucose and increase in the hepatic glycogen content. parenchymatous cells thin walled, isodiametric to circular Dry latex also prevented the loss of body weight in diabetic with intercellular spaces present in ground tissue, stele rats and brought down the daily water consumption to values crescent shaped composed of bicollateral and open vascular comparable to normal rats. Dry latex also produced an bundle, xylem consists mostly of vessels and tracheids, a increase in the hepatic levels of the endogenous antioxidents, strip of cambium present between xylem and phloem tissue, namely superoxide dismutase(SOD), catalase and laticifers also present in phloem and parenchymatous zone. glutathione, while it brought down the levels of the Lamina shows mesophyll differentiated into a palisade and thiobarbituric acid-reactive substances (TBARS) in alloxan- spongy tissue, upper and lower epidermis covered externally induced diabetic rats. The efficacy of dry latex as an with a thick, striated cuticle, spongy parenchyma tissues antioxidant and as an anti-diabetic agent was found almost radially elongated with intercellular spaces, central comparable to the standard anti diabetic drug, cells irregular in shape, laticiers and vascular bundles also glibenclamide28. present scattered in this region19. In one study the various parts of the plant, viz. roots, aerial parts and latex have been evaluated for analgesic activity. Page 20 Gupta Sudesh et al. IRJP 2012, 3 (12) The ethanol extract of aerial parts, chloroform extracts of eosinophils were the main features of haemonchosis in the roots and the aqueous solution of dried latex were tested in sheep. In the sheep treated with single oral doses of 0.01 ml acetic acid induced writhing model and exhibited significant and 0,02 ml/kg body weight of C. procera latex, it analgesic activity. The ethanolic extract of flowers of the significantly decreased the egg production and fewer adult plant found to possess a weak analgesic activity29. Haemonchus worms were found in the abomasums. Although Antipyretic Activity the appetite improved, the hemoglobin concentration and The ethanolic extract of the aerial parts, aqueous extract of serum copper, iron, and zinc levels were still reduced after flowers and aqueous solution of the dry latex of the dry latex therapy with Calotropis latex. Both fresh and aqueous extract of C.procera showed significant antipyretic activity in animal of dried latex were evaluated for their anthelmintic potential models that was comparable to aspirin30. using adult earthworms as test worm. Both fresh and aqueous Anti Inflammatory Activity extract exhibited a dose-dependent inhibition of spontaneous The crude dry latex of C. procera possesses a potent anti- motility and evoked responses to pin-prick. With higher inflammatory activity .The anti-inflammatory activity of doses (100% fresh latex) the effects were comparable with petroleum ether , acetone , methanol and aqueous extracts of that of 3% piperazine. The study suggested that it might be dry latex of C. procera was tested in the carrageenan induced effective against parasitic infections of both animals and srat paw oedema model. All the fractions exhibited rat paw humans caused by Ostertagia, Nematodirus, Dictyocaulis, edema model. All the fractions exhibited anti-inflammatory Taenia, Ascaris and Fasciola. The anthelmintic activity in activity but inhibition of edema was found to be greatest with comparison with levamisole through in vitro and in vivo the acetone and aqueous extracts31. studies and found activity against nematodes36. The anti-inflammatory property of the latex of C. procera Spasmolytic Activity was studied on carrageenin and formalin-induced rat paw The aquas extract of C. procera was evaluated for its oedema model. A single dose of the aqueous suspension of spasmolytic effect using in vitro trachea smooth muscle chain the dried latex was effective to a significant level against the of guinea pigs. The extract(50, 100 & 200 µg/ml) showed a acute inflammatory response32. dose dependent relaxant activity probably exhibited through A chloroform-soluble fraction from C.procera root showed the direct relaxant action on the smooth muscles37. significant dose-related anti-inflammatory activity in rats Antimalarial Activity using the pharmacologic models of carrageenan-induced Following an ethnobotanical approach, screened the ethnolic pedal oedema , cotton pellet granuloma anad formaldehyde- extracts of C. procera leaves, stems roots flowers and flower induced arthritis33. buds, for their in vitro anti malarial activity against Hepatoprotective Activity chloroquine sensitive and chloroquine resistant plasmodium The latex of C.procera was evaluated for its hepatoprotective falciparum strains. In further investigation in vitro effect against carbon tetrachloride(CCL4)induced haemolysis of human erythrocytes have been studied with hepatotoxicity in rats. Subcutaneous injection of CCL4 above extracts. The putative anti-plasmodium activity of the administered twice a week, produced a marked elevation in extracts was correlated to their cytotoxicity as represented by the serum level of aspartate transaminase (AST), factor the in vitro rate of haemolysis38. alpha(TNF-α). Histological analysis of the liver of these rats Antidiarrhoeal Activity revealed marked necroinflammatory changes that were The dry latex of C.procera has been evaluated for associated with increase in the levels of TBARS, PGE2 and antidiarrhoeal activity. Like atropine and phenylbutazone, catalase and decrease in the levels of glutathione (GSH), single oral dose of dry latex 500mg/kg produced a significant superoxide dismutase (SOD) and glutathione peroxidase decrease in frequency of defecation, severity of diarrhea and (GPχ). Daily oral administration of aqueous suspension of afforded protection from diarrhea in 80% rates treated with dried latex (DL) of C. procera at 5, 50 and 100mg/kg doses Castor oil. DL produced a decrease in intestinal transit (27- produced a dose-dependent reduction in the serum levels of 37%) as compared to both normal and Castor oil treated liver enzymes and inflammatory mediators and attenuated the animals. Unlike atropine, dry latex significantly inhibited necro-inflammatory changes in the liver34. castor oil induced enteropooling. However, it did not alter the Hydro-ethanolic extract (70%) of C. procera flower was electrolyte concentration in the intestinal fluid as compared to tested for its hepatoprotective effect against paracetamol- castor oil treated rats39. induced hepatitis in rats. Alteration in the levels of Wound Healing Activity biochemical markers of hepatic damage like SGPT, SGOT, Based on its traditional use, this plant was evaluated for its ALP, bilirubin, cholesterol, HDL and tissue GSH were tested wound healing potential. For this purpose four full thickness in both treated and untreated groups. Paracetamol (2g/kg) has excisional wounds of 8.0mm diameter were inflicted on the enhanced the SGPT, SGOT, ALP, bilirubin and cholesterol back of guinea pigs. Topical application of 20µl of 1.0% levels and reduced the serum levels of HDL and tissue level sterile solution of the latex of c.procera twice daily was of GSH. Treatment with hydro-ethanolic exatract of C. followed for 7 days. The latex significantly augmented the procera flower (200mg/kg and 400mg/kg) has brought back healing process by markedly increasing collagen, DNA and the altered levels of biochemical markers to the near normal protein synthesis and epithelisation leading to reduction in levels in the dose dependent manner. In one study, evaluated wound area thus the study provided a scientific rationale for hepatoprotective activity of chloroform extract of roots of C. the traditional use of this plant in the management of procera against CCL4 induced liver injury and found to wounds40. possess significant protective activity35. Antiasthmatic Activity Anthelmintic Activity Following the ethnobotanical approach, flowers of C.procera The latex of C. procera has been shown to possess have been evaluated for its usefulness in the treatment of anthelmintic activity against Haemonchus contortus infection asthma. A clinical study on human beings showed the good in Najdi sheep. Inappetence, dullness, erosive abomasitis, recovery from the symptoms of asthma41. decreased haemoglobin concentration and increased Page 21 Gupta Sudesh et al. IRJP 2012, 3 (12) 16. Kirtikar K.R. and Basu B.D: Indian Medicinal Plants. M/S Bishen Singh Toxicity Report nd Although C.procera is associated with variety of medicinal Mahendra Pal singh, Dehradun, 2 Edition, pp. 1606-1607 (1935). 17. Anonymous: The Ayurvedic Formulary of India. Part-I, Ministry of virtues, but has been observed to be potentially injurious after Health and Family Welfare, New Delhi, pp. 22-23 (1978). prolonged or chronic use. In one study , the effect of flower 18. Chopra R.N., Chopra I.C., Handa K.L. and Kapoor L.D: Chopra’s extract of plant on testicular function of the Indian desert indigenous drugs of India. UN Dhur and Sons Pvt. Ltd., Calcutta, pp. male gerbil meriones hurrianae. The extract was given orally 87-89 (1958). 42 19. Anonymous: The Ayurvedic Pharmacopoeia of India. Part-I, Vol-I, for 30 days and caused wide spread testicular necrosis . Ministry of Health and Family Welfare, Govt. of India, New Delhi, pp.10-11 (2001). CONCLUSION 20. Sharma A.K: Pharmacognostical studies on the roots of Calotropis In the present scenario, traditional knowledge system in our procera R.Br. In:recent Progress in Medicinal Plants, by DK Majumdar, JN Govil, VK Singh and RK Sharma(Editors), Studium Press LLC, country is fast eroding and there is an urgent needs to USA, Vol.9,pp 253-267 (2005). inventoried, record all ethno-botanical and cultural 21. Edman M.D: Nutrient and cardenolide composition of solvent extracted information among the diverse ethnic communities before Calotropis procera. J.agri. Food. Chem. 313, 509-513 (1983). the traditional cultures is completely lost. Therefore 22. Rastogi R.P. and Mehrotra B.N: Compendium of Indian Medicinal Plants. Central Drugs Research Institute, Lucknow and publication & documentation of information on ethnomedicinal uses will Information Directorate, New Delhi, Vol. 1, pp. 71-72 (1993). help in conserving the knowledge. Many traditional plant 23. Shukla O.P. and Krishnamurti C.R: Properties and partial purification of based remedies are back in use and find increasing bacteriolytic enzyme from the latex of Calotropis procera(Madar). J.Sci. application as source of direct therapeutic agents, as raw indust.Res.20c, 109-112 (1961). 24. Rastogi R.P. and Mehrotra B.N: Compendium of Indian Medicinal materials based for the elaboration of more complex semi Plants. Central Drugs Research Institute, Lucknow and publication & synthetic compounds, as models for new synthetic Information Directorate, New Delhi, Vol. 1, pp. 71-72 (1993). compounds and as taxonomic markers for the discovery of 25. Rastogi R.P. and Mehrotra B.N: Compendium of Indian Medicinal new compounds. 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