Calotropis procera

Synonyms

Asclepias procera, Asclepias procera, Asclepias heterophylla, Calotropis hamiltonii, Calotropis heterophylla, Calotropis inflexa, Calotropis mudari, Calotropis syriaca, Calotropis wallichii, Calotropis procera [2][4]

Vernacular Names:

Malaysia

Remiga, Rembiga

English French Cotton, Mudar Plant, Calotropis, Rubber Bush, Apple of Sodom, Mudar, Madar, King’s Crown, Rooster Tree
Indonesia

Widuri

India

Akra,  Alarka (Sanskrit);  Madar (Hindi)

English Dead Sea Apple, Milkweed, Sodom Apple, Swallow-wort, Indian Milkweed, King’s Crown Kapok
Arabic Oshar
Berber

Torcha, Touza, Ngeyi

French

Calotrope, Fatetone, Pomme de Sodome

German

Wahre Mudarpflanzer, Gomeiner

Italian

Calotropo

Spanish

Algodon extranjero, Cazuela

Turkish

Ipekag

General Information

Description

Calotropis procera is a member of the Asclepiadaceae family. It is a medium sized shrub or small tree that grows up to 4m high with a generally waxy appearance and copious milky sap. The stem is grey-green in colour, smooth, rather crooked and covered with thick corky bark, branching sometime almost from the base. The leaves are grey-green, opposite, alternating, waxy, thick and rounded-ovate. They measure 5-15cm x 4-10cm with a short pointed tip and a heart-shaped base partly clasping the stem; a stiff brush of hairs occur at the base of the midvein. The flowers are white with deep purple blotch at the base of each lobe and deep purple scales between the petals and the stamens; more or less tubular, 5-lobed, measure 2-3cm across, devoid of milky sap. They are grouped in umbels in which the outer flowers open first while the inner do not develop fully. The fruit is a grey-green bladdery pod measuring 8-12cm long, rounded at the base but shortly pointed at the tip and containing numerous seeds. The seeds are brown, flattened, with a tuft of long white hair at one end.[4]

Plant Part Used

Root, root-bark, bark, leaves and leaf juice and flowers [1][2]

Chemical Constituents

Akundaric acid; akundrol; akundarol isovalerate; calotropin; caoutchouc; madaralbum; madarfluavil; mudaric acid; mudarine; mudarol isovalerate; mudrol; pekilocerin A; silver salt; uscharidin; uzarigenin; uzarigenin 3-O[b-D-glucopyranosyl-(1->2)-b-D-glucopyranoside]; voruscharin. [1][2][5][6]

Traditional Used:

Gastrointestinal Diseases

Powdered root of C. procera had been used as a remedy for dysentery but traditional practitioners warn of the prevailing side effects which are very much similar to those of ipecacuanha i.e. vomiting and depression with bilious stools. Some advocate the use of tinctures of the roots, however, it seems that the powdered root is superior in its effects. In Gambia, the young leaves boiled in water and mixed with cook rice seem to be the remedy for dysentery. The root bark is regarded as an excellent medication for colic and stomach problems in some African countries; in Sudan it is used for jaundice. For intestinal worm infestation, the Kusasi of Ghana make a salve from root and leaf ash with shea butter that is rubbed into scarifications on the abdomen of children. Unani medicine advocate the use of the roots to treat haemorrhoids, tape worms and the root decoction is used to treat ancylostomiasis (worm disease).[2][3][7]

Respiratory Diseases

Asthma is treated by using either the flowers or the roots in a decoction. A decoction of the leaves is given to relieve cough. For whooping cough the leaves are boiled with Momordica charantia and the decoction is drank a glassful each time. The root is also good for asthma and cough according to Unani medicine. In Egypt the dried leaves are smoked in pipes for relieving cough.[3][7]

Infectious Diseases

C. procera is popularly used to treat leprosy in Africa. Various methods had been employed for this. In Bamako, the patient is bathed with an 8-day macerate, and in Senegal the patient is given a diluted decoction of the roots. The Gambians uses the juice of the boiled leaves as a remedy for leprosy. There are others who advocate the writing of Quranic verses on the leaves before boiling. The root is also used in the treatment of venereal diseases like gonorrhea and syphilis. In these cases the root or root bark is fermented in honey and given to the patient to drink.[3]

Other uses

A remedy for snake bite is to take the root with black pepper in the dose of 5 to 10 grains. For women with hypermenorrhoea the dried leaves are used to control the bleeding while in cases of amenorrhoea a decoction of the leaves mixed with shea butter is given. In cases of dystochia a little of the powdered roots mixed in water is prescribed to be given 15 minutes after delivery. In Sudan the latex is used to procure abortion. The stem bark is considered an aphrodisiac while the dried flowers is a remedy for impotency. The Nubians made use of the latex to cure toothache and to loosen the tooth to facilitate extraction; the Pathans on the other hand used fresh roots as toothbrush to prevent and cure toothache. Circulatory and cardiac problems are treated with diluted extract of the root bark. An infusion of one leaf in one glass of water is drunk against arterial hypertension.[2][3]

Pre-Clinical Data

Pharmacology

Anti-inflammatory activity

The flowers, the roots and the latex of C. procera all have anti-inflammatory activities. This fact had been proven a few studies. [9-11] A study [12] concluded that the anti-inflammatory effects of dried latex of C. procera was due to its ability to inhibit histamine and bradykinin and partially inhibiting prostaglandin E2. Another study [13] identified the active anti-inflammatory compound to be protein in nature. They found that the protein was able to inhibit neutrophil migration induced by carrageenin. On the basis of this they suggested that in inhibitory effect of the latex is likely to be cell-mediated. Reports concurred with this finding and suggested that this effect is mediated through NO production.

Antipyretic, analgesic and neuromuscular blocking activity

A study on the analgesic and antipyretic effects of their ethanolic extract of the flowers of C. procera by using the ethanol extract of the plant to show a significant antipyretic, analgesic and neuromuscular blocking activity. [9][14] Two studies [15] [16] focused on the analgesic properties of the dry latex. They showed that the anti-nociceptive effect was not dependent on the opiod system.

Antitussive activity

A study [17] found that the aqueous extract of the stem bark was able to suppress cough induced by bronchial irritation by ammoniac in Guinea pig.

Antiulcerogenic activity

The chloroform fraction of C. procera root extract showed significant anti-ulcer activity against aspirin, indomethacin, ethanol, indomethacin + ethanol and stress-induced ulceration. A study [18] found that the extract not only inhibit gastric secretory volume and total acidity, it also inhibited arachidonic acid metabolism making the inhibition of 5-lipoxygenase as a probable mechanism for its anti-ulcer activity. Bharti et al. [19] found that the dried latex of C. procera has the therapeutic potential to relieve gastric hyperacidity and to prevent gastric ulceration induced by necrotizing agents.

Antidiarrhoeal activity

A single dose of dry latex of C. procera was able to significantly decrease the frequency of defaecation, the severity of diarrhea and afforded protection from diarrhea in 10% of rats treated with castor oil. This was achieved through reduction in intestinal transit and inhibition of castor oil induced intestinal fluid accumulation.[20]

Wound healing activity

A study [21] on application of 20 microl of 1% sterile solution of the latex of C. procera on full thickness wound of rats twice daily for 7 days found that there was augmentation of healing process through  marked increase in collagen, DNA and protein synthesis and epithelisation leading to reduction of wound area.

Antifertility activity

Studies [22] involving ethanol and aqueous extracts of C. procera roots to study their effect on oestrous cycle and on some parameters of oestrogenic functionality in rats. There was evidence of interruption in normal oestrous cycle by both extracts through prolongation of the dioestrous stage of the oestrous cycle with consequent temporary inhibition of ovulation. Another study [23] found their ethanol extract of the roots did not show andy antioestrogenic activity, however, there was evidence of strong anti-implantation and uterotropic activity at dose level of 250mg/kg.

Cardioprotective activity

A study [24] found that by pretreating albino rats with 300mg/kg of ethanol extract of latex of C. procera thrice daily for 30 days, there was significant reduction in the elevated marker enzyme levels in serum and heart homogenates in isoproterenol-induced myocardial infarction. Histopathological studies showed a marked protection by the extract against myocardial necrotic damage.

Smooth muscle relaxant activity

A study [14] reported earlier the ability of their ethanol extract to induce smooth muscle relaxation. Another study [25]demonstrated similar activity with their ethanol extract of the plant. They believe this could be through direct relaxant action on the smooth muscle. Studies [26] found that the oral administration of dry latex decreased intestinal transit time and also decrease intestinal content. At lower doses there was a dose-dependent contractions of gastrointestinal smooth muscles that was followed by desensitization at higher doses.

Antioxidant activity

C. procera exhibit anti-oxidant activity. Study [27] found this activity in their dry latex, while Qureshi et al. [28] showed this activity in their ethanol extracts of the flowers.

Antidiabetic activity

Roy et al. [27] studied on the effects of the dry latex of C. procera on the blood glucose levels in alloxan-induced diabetic rats. Daily oral dose of the dry latex at 100mg/kg and 400mg/kg reduced the blood glucose level and increased hepatic glycogen content. At the same time it also prevented the loss of body weight and reduced daily water consumption to normal rat’s levels.

Hepatoprotective activity

A number of workers studied the hepatoprotective activity of C. procera. Both studies [28][29] on the effects of their ethanol extracts of the flowers against liver damage induced by CCl4 and paracetamol respectively. Their results were similar i.e. there was reduction of the biochemical markers of hepatic injury (serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, bilirubin, cholesterol, HDL and tissue glutathione (GSH) levels.). The presence of quercetin related flavonoids could be play a role in this hepatoprotective activity. Padhy et al. [30] working on the latex also found liver protective activity in it.

Cytotoxicity activity

The roots and latex of C. procera exhibited cytotoxic activity. In their studies of the methanol extracts of the roots, Van Quaquebeke et al. [31] managed to isolate cardenolide which had antitumout activity together with inhibitory influence on the Na+/K+ ATPase activity. Cardenoline was found to be active against 57 human cancer cell lines. Mathur et al. [32] found their root extracts were active against Hep2 cells and this is due to its ability to cause apoptosis and disruption of cell cycle at S phase preventing cells from entering G2/M phase. Choedon et al. [33] found that their methanol extract of the latex could protect their X15-myc transgenic mice against hepatocarcinogenesis without any adverse effects. There was extensive cell death in both Huh-7 and COS-1 cells with extensive fragmentation of DNA in both. The laticifer proteins [34] (LP) isolate from the latex showed considerable cytotoxic activity on SF295 and MDA-MB-435 cell lines. LP was found to express its cytotoxic activity through inhibition of DNA synthesis by alteration in the topology of DNA. It was also found to inhibit topoisomerase I activity.

Antimicrobial activity

A study [9] had earlier reported the antibacterial activity of their ethanol extracts of the flowers of C. procera. It could inhibit the growth of both Gram-positive and Gram-negative bacteria. Another study [35][36] found the Calotropis procera had the most effective antibacterial properties as compared to other Moroccan medicinal plants they studies.

Toxicities

Toxicity studies of latex of Calotropis procera

The latex has a direct irritant action on the mucous membrane particularly in the eye. Skin reactions to this plant may be caused by allergy rather than to a direct irritant action. All parts of the plant contain a cardioactive steroid and calcium oxalate crystals. Toxin: An unidentified vesicant allergen in the latex, calcium oxalate crystals and cardioactive steroids resembling digitalis.

Clinical Findings

Human intoxication from this plant have been reported in modern times. Ingestion of calcium oxalates causes a painful burning sensation of the lips and mouth. There is an inflammatory reaction, often with oedema and blistering. Hoarseness, dysphonia and dysphagia may result. Poisoning would be expected to produce clinical findings typical of cardioactive steroids. Toxicity has a variable latent period that depends on the quantity ingested. Dysrhythmias include sinus bradycardia, premature ventricular contractions, atrio-ventricular conduction defects, or ventricular tachydysrhythmias. Hyperkalemia, if present, may be an indicator of toxicity.

Management

Calcium oxalate toxicity: the pain and oedema recede slowly without therapy. Cool liquids or demulcents held in the mouth may bring some relief. Analgesics may be indicated. The insoluble oxalate in the plants does not cause systemic oxalate poisoning.

Cardioactive steroid toxicity: Gastrointestinal decontamination as appropriate, serial electrocardiograms, and serum potassium determinations should be performed. If serious cardioactive steroid toxicity is considered, digoxin-specific Fab should be administered. Consultation with a Poison Control Center should be considered.[7]

Clinical Data

Clinical Trials

No documentation

Adverse Effects in Human:

A report of adverse reaction to the drug was made by Behl et al. [5]. A 76 year old male developed severe dermatological lesions of the skin and mucous membranes following ingestion of burnt leaves of C. procera for two weeks. The lesions appeared as flaccid blisters on non-inflammatory base over the back with eroded and crusted lesions ocvee the rest of the body. Nikolsky’s was positive. Lesion developed from the mouth spreading all over the body except the palms and soles; genital and conjuctival mucosae.

C. procera induced keratitis was reported by a number of workers.[37-40] The clinical picture of this keratitis include painless dimness of vision with photophobia, conjunctival congestion and mild to severe corneal oedema. This could subsequently lead to epithelial defect, iridocyclitis and secondary glaucoma as complications. All workers agreed that this is reversible provided the latex did not penetrate the corneal stroma and induce permanent loss of endothelial cells. Treatment with local steroid drops seems to be the best way of handling this situation. Basak et al. [39] advocate to use anti-glaucoma agents, cycloplegics, hypertonic saline and tears supplement to address any prevailing complications.

Used in Certain Conditions

Pregnancy / Breastfeeding

No documentation

Age Limitations

Neonates / Adolescents

No documentation

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

No documentation

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

No documentation

Case Reports

No documentation

References

    1. Botanical: A Modern Herbal. http://www.botanical.com/botanical/mgmh/c/calotr09.html [Accessed on 3/3/2010]
    2. H. Panda,  Medicinal Plants Cultivation & Their Uses, Asia Pacific Business Press, Delhi, 2000. pg231-234
    3. Hans Dieter Neuwinger, African ethnobotany: poisons and drugs : chemistry, pharmacology, toxicology, CRC Press, Stuttgart, 1996.  pg 226-228
    4. William Thomas Parsons, Eric George Cuthbertson, Noxious weeds of Australia, CSIRO Publishing, Collingwood,  2001. pg173-174
    5. Indian Journal of Dermatology, Veneorlogy and Leprology. http://www.ijdvl.com/article.asp?issn=0378-6323;year=2002;volume=68;issue=3;spage=150;epage=151;aulast=Behl [Accessed on 3/3/2010]
    6. Viqar Uddin Ahmad, Anwer Basha Spectroscopic Data of Steroid Glycoside, Volume 4 Sppringer Science and Business Media New York 2006 pgs. 2337, 2403, 2663, 2665, 2717
    7. Lewis Nelson, Richard D. Shih, Micheal J. Balick, Handbook of Poisonous and Injurious Plants Springer – Verlag New York 2007 pg. 103 – 104
    8. NIIR Board of Consultants and Engineers Handbook on Unani Medicines with Formulae, Processes, Uses and Analysis Asia Pacific Business Press Delhi pg. 300
    9. Mascolo N, Sharma R, Jain SC, Capasso F. Ethnopharmacology of Calotropis procera flowers. J Ethnopharmacol. 1988 Feb-Mar;22(2):211-21.
    10. Basu A, Chaudhuri AK. Preliminary studies on the antiinflammatory and analgesic activities of Calotropis procera root extract. J Ethnopharmacol. 1991 Mar;31(3):319-24.
    11. Kumar VL, Basu N. Anti-inflammatory activity of the latex of Calotropis procera. J Ethnopharmacol. 1994 Oct;44(2):123-5.
    12. Arya S, Kumar VL. Antiinflammatory efficacy of extracts of latex of Calotropis procera against different mediators of inflammation. Mediators Inflamm. 2005 Aug 31;2005(4):228-32.
    13. Alencar NM, Figueiredo IS, Vale MR, Bitencurt FS, Oliveira JS, Ribeiro RA, Ramos MV. Anti-inflammatory effect of the latex from Calotropis procera in three different experimental models: peritonitis, paw edema and hemorrhagic cystitis. Planta Med. 2004 Dec;70(12):1144-9.
    14. Mossa JS, Tariq M, Mohsin A, Ageel AM, al-Yahya MA, al-Said MS, Rafatullah S. Pharmacological studies on aerial parts of Calotropis procera. Am J Chin Med. 1991;19(3-4):223-31.
    15. Dewan S, Sangraula H, Kumar VL. Preliminary studies on the analgesic activity of latex of Calotropris procera. J Ethnopharmacol. 2000 Nov;73(1-2):307-11.
    16. Soares PM, Lima SR, Matos SG, Andrade MM, Patrocínio MC, de Freitas CD, Ramos MV, Criddle DN, Cardi BA, Carvalho KM, Assreuy AM, Vasconcelos SM. Antinociceptive activity of Calotropis procera latex in mice. J Ethnopharmacol. 2005 May 13;99(1):125-9.
    17. Dieye AM, Tidjani MA, Diouf A, Bassene E, Faye B. [Senegalese pharmacopoeia: study of acute toxicity and antitussive activity of Calotropis procera AIT (Asclepiadaceae)] Dakar Med. 1993;38(1):69-72.
    18. Sen T, Basu A, Chaudhuri AK. Studies on the possible mechanism of the gastric mucosal protection by Calotropis procera--involvement of 5-lipoxygenase pathway. Fundam Clin Pharmacol. 1998;12(1):82-7.
    19. Bharti S, Wahane VD, Kumar VL. Protective effect of Calotropis procera latex extracts on experimentally induced gastric ulcers in rat. J Ethnopharmacol. 2010 Feb 3;127(2):440-4.
    20. Kumar S, Dewan S, Sangraula H, Kumar VL. Anti-diarrhoeal activity of the latex of Calotropis procera. J Ethnopharmacol. 2001 Jun;76(1):115-8.
    21. Rasik AM, Raghubir R, Gupta A, Shukla A, Dubey MP, Srivastava S, Jain HK, Kulshrestha DK. Healing potential of Calotropis procera on dermal wounds in Guinea pigs. J Ethnopharmacol. 1999 Dec 15;68(1-3):261-6.
    22. Circosta C, Sanogo R, Occhiuto F. Effects of Calotropis procera on oestrous cycle and on oestrogenic functionality  in rats. Farmaco. 2001 May-Jul;56(5-7):373-8.
    23. Kamath JV, Rana AC. Preliminary study on antifertility activity of Calotropis procera roots in female rats. Fitoterapia. 2002 Apr;73(2):111-5.
    24. Ahmed KK, Rana AC, Dixit VK. Effect of Calotropis procera latex on isoproterenol induced myocardial infarction in albino rats. Phytomedicine. 2004;11(4):327-30.
    25. Iwalewa EO, Elujoba AA, Bankole OA. In vitro spasmolytic effect of aqueous extract of Calotropis procera on Guinea-pig trachea smooth muscle chain. Fitoterapia. 2005 Mar;76(2):250-3.
    26. Kumar VL, Shivkar YM. In vivo and in vitro effect of latex of Calotropis procera on gastrointestinal smooth muscles. J Ethnopharmacol. 2004 Aug;93(2-3):377-9.
    27. Roy S, Sehgal R, Padhy BM, Kumar VL. Antioxidant and protective effect of latex of Calotropis procera against alloxan-induced diabetes in rats. J Ethnopharmacol. 2005 Dec 1;102(3):470-3.
    28. Qureshi AA, Prakash T, Patil T, Viswanath Swamy AH, Gouda AV, Prabhu K, Setty SR. Hepatoprotective and antioxidant activities of flowers of Calotropis procera (Ait) R. Br. in CCl4 induced hepatic damage. Indian J Exp Biol. 2007 Mar;45(3):304-10.
    29. Ramachandra Setty S, Quereshi AA, Viswanath Swamy AH, Patil T, Prakash T, Prabhu K, Veeran Gouda A. Hepatoprotective activity of Calotropis procera flowers against paracetamol-induced hepatic injury in rats. Fitoterapia. 2007 Dec;78(7-8):451-4.
    30. Padhy BM, Srivastava A, Kumar VL. Calotropis procera latex affords protection against carbon tetrachloride induced hepatotoxicity in rats. J Ethnopharmacol. 2007 Sep 25;113(3):498-502
    31. Van Quaquebeke E, Simon G, André A, Dewelle J, El Yazidi M, Bruyneel F, Tuti J, Nacoulma O, Guissou P, Decaestecker C, Braekman JC, Kiss R, Darro F. Identification of a novel cardenolide (2''-oxovoruscharin) from Calotropis procera and the hemisynthesis of novel derivatives displaying potent in vitro antitumor activities and high in vivo tolerance: structure-activity relationship  analyses. J Med Chem. 2005 Feb 10;48(3):849-56.
    32. Mathur R, Gupta SK, Mathur SR, Velpandian T. Anti-tumor studies with extracts of Calotropis procera (Ait.) R.Br. root employing Hep2 cells and their possible mechanism of action. Indian J Exp Biol. 2009 May;47(5):343-8.
    33. Choedon T, Mathan G, Arya S, Kumar VL, Kumar V. Anticancer and cytotoxic properties of the latex of Calotropis procera in a transgenic mouse model of hepatocellular carcinoma. World J Gastroenterol. 2006 Apr 28;12(16):2517-22.
    34. Soares de Oliveira J, Pereira Bezerra D, Teixeira de Freitas CD, Delano Barreto Marinho Filho J, Odorico de Moraes M, Pessoa C, Costa-Lotufo LV, Ramos MV. In vitro cytotoxicity against different human cancer cell lines of laticifer proteins of Calotropis procera (Ait.) R. Br. Toxicol In Vitro. 2007 Dec;21(8):1563-73.
    35. Larhsini M, Oumoulid L, Lazrek HB, Wataleb S, Bousaid M, Bekkouche K, Markouk M, Jana M. Screening of antibacterial and antiparasitic activities of six Moroccan medicinal plants. Therapie. 1999 Nov-Dec;54(6):763-5
    36. Larhsini M, Oumoulid L, Lazrek HB, Wataleb S, Bousaid M, Bekkouche K, Jana M. Antibacterial activity of some Moroccan medicinal plants. Phytother Res. 2001 May;15(3):250-2.
    37. Al-Mezaine HS, Al-Rajhi AA, Al-Assiri A, Wagoner MD. Calotropis procera (ushaar) keratitis. Am J Ophthalmol. 2005 Jan;139(1):199-202.
    38. Pandey N, Chandrakar AK, Garg ML, Patel SS. Calotropis procera -induced keratitis. Indian J Ophthalmol. 2009 Jan-Feb;57(1):58-60.
    39. Basak SK, Bhaumik A, Mohanta A, Singhal P. Ocular toxicity by latex of Calotropis procera (Sodom apple). Indian J Ophthalmol. 2009 May-Jun;57(3):232-4.
    40. Al-Mezaine HS, Al-Amry MA, Al-Assiri A, Fadel TS, Tabbara KF, Al-Rajhi AA. Corneal endothelial cytotoxicity of the Calotropis procera (ushaar) plant. Cornea. 2008 May;27(4):504-6.