Umbels : cottony, Old glabrous, long peduncle

Corolla : lobes erect, Coronal scale, glabrous or pubescent

Follicles : 8.5 – 10.5 cm, recurved

Seeds : Ovoid³

The flowers are large, beautiful lilac or purple tinged, arranged in umbellate corymbs on erect cylindrical shoot peduncles³

The fruits are short, Ovoid, curved, thick, fleshy follicles covered with white woolly pubescence.³

It is common in western and central India from Punjab to often found as a weed in agricultural lands. The plant of Caltrops procure are shown in figure no1.

Figure no1: Caltrops procure

Chemical Constituents:

Ethanolic extracts of flowers, buds and roots of Calotropis procera contain alkaloids, carbohydrates, glycosides, phenolic compounds/tannins, proteins and amino acids, flavonoids, saponins, sterols, acidic compounds and resins.

A yellow bitter resin, a black acid resin, madaralbum, a crystalline colourless substance, madarfluavil, an crystalline coloured substance, caoutchouc, and a pewliar principle which geletinizer on heating, called Mudorine. Lewin found a neulral principal, calatropin, a veery active poison of digitalis type.

Pentacyclic triterpenes, alkaloid, cardinolides, phytosterols, triterpenoid saponin have found in root extract ¹²

Latex is chemically composed of various compounds like cardenolides, proteolytic enzymes.

It contains a number of cardioactive glycosides, calactin, calolropain, calotropagenin, proceroside, syriogenine, calotoxin, uscharin, uzarigenin, voruscharin, tannins, flavonoids, sterols and /or triterpenes.¹⁴

Other compounds found were benzoylisolineolon and benzoyllineolone¹⁵, procesterol¹⁶, a steroidal hydroxyl ketone¹⁷, flavonol glycosides¹⁷, organic carbonate along with stigmasterol and B – sitosterol¹⁸, and procerain, a stable cysteine protease.¹⁷

Essential elements Al, As, Cu, Ca, Cr, Cd, Fe, K, Mn, Na, Pb and Zn have been analyzed from C. procera in variable range.⁴

Two phyto constituents Procero rsenyl. Acetate, urs-18 X H-12, 20(30)-diene-3B-yl acetate, Proceranol, N-triacontan-10B-01) have be reported from roots of Calotropis procera as natural productions.²⁰

Pharmacological Activities:

Antipyretic activity:²¹

Hyperpyrexia was induced in mice by 20 ml/kg S.C. administration of a 20 % aqueous suspension of brewer’s yeast. These animals were then fasted for the duration of experiment. The rectal temperatures were taken 24 hr after yeast injection to determine the pyretic response to yeast Temperature taken 1 h prior to drug administration infevered animals served as pre-drog control. Plant extract was administered orally in a dose of 500 mg /kg body weight and temperatures were recorded at 30, 90 and 150 min flowing drug administration. Thus, ethanolic extract of C. procera produced significant reduction of yeast induce increase in body temperature suggesting its antipyretic activity.²¹

Analgesic activity:²¹

The hot plate method described by Torner (1965) was seed for the determination of analgesic activity: The animals were dropped gently on a hotplate and maintained at 55± 0.5⁰C. The reaction time was taken as the interval extending from the instant the animal reaches the hot plate till the moment the animal licks its fore text or jumps out. The reaction time is measured to the nearest 1/5 sec, 10 min before oral administration of drug (plant extract) 500mg 1 kg and at 30,40 and 150 min thereafter. There was a significant increase in reaction time of the treated mice placed on hot plate confirming analgesic activity of extract.²¹

Anti- inflammatory activity:²²

The DL of Calotropis procera inhibited the formation of paw-odema to significant level in rat treated either with carrageenin or formalin. At a dose of 5mg/rat, the DL produced 71% inhibition in the case of the carageenin – induced odema (p<0.005). However, at higher dose (50mg/rat), the anti inflammatory effect of 02 was comparably in both carageenin and formalin induced odema groups, i.e, 96% and 98% respectively. Furthermore the DL mediated inhibition of the carrageenin induced odema was 1.3 fold better as compared to phenyl butazone. Thus, showing a significant anti – inflammatory activity ²².

Protective activity on gastric ulcers:²²

The latex collected from the aerial parts of the plant growing in wild was air dried under shade at ambient temperature, ground to small granules (DL) and subjected to sequential soxhlation with petroleum ether and methanol. The methanol extract thus obtained was dried (Me DL). Both DL and Me DL were triturated in normal saline for oral administration in rats and their PH was found to be 5.8 and 4.5 respectively. Hastric lesions were induced in rats by oral administration of DL and Me DL produced a significant does-dependent decrease in extent of gastric mucosal damage in both ethanol and aspirin models. In ethanol model both DL and Me DL were more effective than famotidine and produced 96% and 81% in gastric ulceration of 100 and 50 mg lkg dose respectively as compared to 63% inhibition in famotidine treated group. The effect of DL and Me DL was comparable in aspirin model where 70-80% inhibition was observed against 99% inhibition in famotidine treated group. The effect of DL and Me DL was comparable in aspirin in famotidine treated group. Thus, dried latex and Methanolic extract of latex of C. procera shows protective effect on gastric ulcers.²²

Protective effect on gastric hemorrhage:²²

Oral administration of alcohol produced gastric hemorrhage with a median score of 9 in the EC group against 0 in NC group. Treatment of rats with dried later and Methanolic extract of later (Me DL) of C. procera produced a significant decrease in gastric hemorrhage and a median hemorrhagic score of 1 and 2 was obtained in DL 100 and Me DL 50 group respectively. Thus dried later and Methanolic extract of later of C. procera shows protective effect on gastric hemorrhage. ¹⁸

Anthelmintic activity:²³

In-vitro trials demonstrated time dependent anthelmintic. Activity booth of Calotropis Aqueous Extract (CAE) and Calotropis Methanolic Extract (CME) of Calotropis proura flowers against Haemonchus contortus. In vitro paralysis of Oesophagostomum colombianum and Bunostomum trigonocephalum in 4 and 6h, respectively was reported on post exposure to 1% calotropain isolated from latex of Calotropis procera. 24 fresh as well as aqueous extracts of dried latex of Calotropis procera. Exhibited a dose dependent inhibition of spontaneous motility (paralysis) of earth worms the effect of higher doses (100mg/ml of ags. Extract of dry later and 100% fresh later) were comparable with that of 3% piperazine. ²⁵

A concentration dependent larvicidal activity against Haemonchus contortvs in vitro with in 20 min of application of Calotropis procera later was shown, and significant reduction in egg production and lesser worm burden in sheep experimentally infected with Haemonchus contortus and treated with single oral dose of 0.01ml or 0.02mml/kg body wt of C. procera later was observed.²⁶

Anti–diarrheal activity:- ²⁷

DL of C. procera produced a marked anti-diarrheal effect in rats. DL significantly decreased the total number of stools passed (2.2 + 0.7) as compared to the castor oil treated control group(6.+0.8) The effect of DL was comparable to that of PBZ(1.8+0.8) Atropine at a dose of 0.1 mg/kg,i.p produced marked anti-diarrheal effect (1.0+0.6) (Table 1). Besides deereasing the number of stools passed, DL also afforded protection against the castor oil induced diarrhea. The effect of castor oil was discernible at 2 h when 40% animals showed diarrhea. And by fourth hour 80% of rats showed diarrhea. DL delayed the onset of diarrhea and only 20% rats showed diarrhoea at third and fourth hour. The effect of atropine and PBZ was comparable and only 20-25% rats showed diarrhea at fourth hour (Fig.1). DLwas also found to pos sess anti-enteropooling activity. Oral administration of castor oil produced a significant increase in the intestinal fluid (2.6+0.2ml) as compared to normal rats (1.2+0.1ml).DL, when given orally I h before castor oil, significantly inhibited the enteropooling (1.3+0.1ml: p+0.001) and the volume of intestinal fluid was comparable to that obtained in nirmal group (1.2+0.13) (Table 2). The weight of intestinal content also obtained by subtracting the weight of empty intestine form that of full intestine. The weight of intestinal content was also significantly increased following treatment with castor oil (2.9 + 0.2 vs. 1.10+0.01g in normal rats). However, DL produced marginal decrease in the weight of intestinal content. The secretions were more viscous and the intestinal wall was thinner. DL also decreased the propulsion of charcoal meal through gastrointestinal tract when compared to the normal and castor oil treated rats. The percentage of intestinal length traversed by charcoal meal in DL pretested, normal and castor oil treated rats was 63+4.8, 99.4+0.6 and 87.1+7.5, respectively. Atropine on the other hand, produced a marked decrease in the propulsive movements and the intestinal length traversed by charcoal meal was 23.3+3.1%. Treatment of rats with castor oil significantly increased the Na+ concentration to 11.0+0.7 mEq/ I as compared to the control group (7.2+0.6mEq/ I). DL as well as atropine pretreatment did not alter the Na+ concentration in intestinal fluid as compared to the castor oil treated group. None of the treatments produced a significant change in the K+ concentration although it was low in atropine pretreated rats. Thus, the DL of c.procea possessa significant anti- dirroteal anti litry due to its inhibitory effect both on 4IIpropvision and fhid seorehion.

Anti fertility activity:²⁸

Calotropis procera, roots possesses a significant estrogenic activity shown by its uterotropic effects in immature femal rats and by its ability to increase the weight to genital organs in ovariactomized rats. Both activities were confirmed by the potentiation of effect of ethynyilestradiol, CPA also possess a very strong anti implantation activity (100%) which may be due to its estrogenic activity. In fact, it is well known that estrogenic substances inhibit pregnancy by suppressing the level of both follicle stimulating hormone (FSH), and luteinizing hormone (LH), which in turn present implantation. ²⁸

Carbachol (CAR: 1.1 x 10^-10 – 4.4 x 10^-10 M), histamine (HIST : 1.8 x 10^-10– 7.2 x 10^-10 M) and KCL (2.7 x 10^-10– 2.0 x 10^-10 M) contracts the smooth muscle does–dependently. The aqueous extract of Calotropis procera (AECP: 50 – 20 g ug/ml) inhibited both CAR (4.4 x 10^-10 M) – and HIST (7.2 x 10^-10 M) – induced contractions without any effect on contractions induced by KCL (2.0 x 10^-9 M). Propranolol, at dose also able to reduce the relaxant effect of ah₂ – stimulant (PROP 3.4 x 10^-11 M) dose not affect the AECP effect on CAR- induced contractions. This result seems to suggest that AECP is not acting through h-receptor. On the contrary, the AECP effect was increased in presence of amnophylline (AML : 1.2 X 10 -10M) indicating that AECP is probably aching through direct relaxant mechanism mediated by xanthine – like product. Thus, the aqueous extract of whole c. procera exhibited a relevant activity on guinea pig trachea smooth chain supporting the claim that the plant is endowed with spasmolitic activity. ²⁹

Healing potential on dermal wounds: ³⁰

Topical application of C. procera at the wound site produced significant wound healing activity, which may be due to its angiogenic and mitogenic potential. Its prohealing activity was conspicuous as all observed healing parameter were significantly affected. The wound after 7 days treatment with plant extract exhibited marked dryness of wound edges with regeneration of healing tissue and the wound area was also considerably reduced compared to controls indicating the healing potential of calotropis. The protein and DNA contents of granulation tissue indicate the levels of protein synthesis and mutagenic profile of plant extract and that this action of plant material significantly contributes to wound healing. This might be due to cellular infiltration as well as replication of cells in healing process- in the treated group as revealed by histological observation of granulation of granulation tissue. It also showed elevated levels of hydroxyproline by about 50% in regenerated tissue suggests enhanced collagen synthesis, an important constituents of extracellular matrin collagen. Collagen not only confers strength and integrity to tissue matrin but also plays an important role in homeostasis and in epithelisation at late phase of wound healing. A close examination of granulation tissue sections revealed that the tissue regeneration was much faster in treated group compared to control wounds. There was marked infiltration of inflammatory cells, increased blood vessel formation and enhanced prolifltration of fibroblasts as a result of calotropis treatment. The great degree of epithelial cell observed in calotropis treated wounds signifies prohealing activity of plant material. The extract also appears to stimulate significant reduction in wound size which might be due to enhanced epithelisation. Therefore it appears that the calotropis extract possesses significant prohealing activity by affecting the healing at various phases of tissue repair.³⁰

Protective effect on myocardial infarction: ³¹

The alcoholic extract of the later of plant Calotropis procera was evaluated for protection against isoproterenol (20mg/100gm body wt, S.C) induced myocardial infarction in albino rats. The heart damage induced by isoproferenol was indicated by elevated level of marker enzymes such as creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), serom glutammte oxaloacetic transaminase (SGORT ) and serom glutamate pyrouvate. Transaminase (SGPT) Insertion with increase lipid peroxide and reduced Glutathione content in heart homogenates. Microscopical examination (histopathology) was also performed on myocardial tissue. Pretreatment with an ethanolic later extract of Calotropis procera at dose of 300 mg/kg body wit, administered orally thrice a day for 30 days, reduced significantly (p<0.01) the elevated marker enzyme level in serum and heart homogenates in isoproternol – induced myocardial infarction. An increase in level of marker enzyme in serum could be due to leakage of enzymes from the heart as a result of isoproterenol – induced necrosis. An increase level of lipid persoxide in heart following isoproterenol administration indicates enhanced lipd peroxidation by free radicals. Due to this increased lipid peronidation decreases lipid peroxide in heart following isoproterenol administration indicates enhanced lipid peroxidation, gluatathione levels are lowered. CPLA pretreatment decreases lipid peroxide and maintained glutathione levels. Histropathological observation revealed a marked protection by the extract in myocardial necrotic damage.³¹

Anti-diabetic effect of C. procera:³²

Dried latex of C. procera showed anti-hyper glycemic and increased level of hepatic glycogen in diabetic rates. Treatment of rates with alloxan produced a significant increase in blood glucose level within 3 days. The levels of blood glucose in diabetic control rates were 12.9+- 1.3 mmol/litre as compared to 5.4+-0.3 mmol/L in normal rates (P<0.01) and alloxan also produced a significant decrease in liver glycogen levels in comparison to normal control group (3.3+-1.4 mglg tissue versos 14.7+-0.3 mglg tissue, P<0.01). Treatment of diabetic rates with DL produced a dose dependent decrease in level of blood glucose and a dose dependent increase in level of hepatic glycogen. The antihyperglycemic effect of DC was discernible within 3 days of treatment, comparable to standard anti-diabetic drug glibenclamide. Also, the glycogen levels were 7.5+-1.3 and 14.4+-0.5 Mg/tissue in DL 100 and DL 400 mg/kg treated rates with DL shows anti-diabetic effect. 32

Parasympathomimetic activity:²¹

The effect Ethanolic extract of aerial parts of C. procura was studied by using isolated guinea pigileum (Ghosh,1984). It showed contractions of isolated smooth muscle guinea pig lieum which was antagonized by atropine. These findings suggest parasympathonimetic activity of C. proura.

Neuromuscular blocking activity:

The effect of Ethanolic activity of aerial parts of C. procura was tested using frog’s isolated rectus abdomens muscle preparation and rat phrenis nerve diaphragm preparation. (Ghosh 1984). It showed neuromuscular blocking activity.

Anti-cancer activity (Hepatocellular carcinoma):

Dried later treatment of showed a complete protection against heapatocarcinogeniesis. No adverse effect was observed in these animals. The sarcoma vascular endothelial growth factor (VEGF) level was significantly lowered in treated mice as compared to control animals. Cell culture studies revealed that the methanolic extract of DL as well as its fraction induced extensive cell death in both hepatoma (Huh7) and non-hepatoma (Cos-1) cells while non-transferred hepatocytyes (AMLI2) cells were spared. This was accompanied by extensive fragmentation of DNA in Huh7 and cos– 1 cells. No change in levels of canonical markers of apoptosis such as Bcl2 and Capawse 3 was observed. DL of C. procera has the potential for anti-cancer therapy due to its differentiable targets and non-intergerence with regular pathway of apoptosis.

Other Pharmacological actions;-

1. The latex plant is used as an anti-dysentric, antirheomatic, a diaphoretis, an expectorant and for treatment of bronchial asthma and skin conditions, analgesic.

2. It also exhibits pleiotropic effects.

3. It also has antibacterial, nematocidal and lorvicidal activities.

4. In African and Asian Countries, the latex of C. procera is utilized as a arrow poison molluscide, a fungicide, an anti-syphilitic, a purgative, for treatment of lepers and bronchial asthma and for milk adulation in cheese making.

5. Milky juice is reported for the treatment of dropsy and rheumatism to remove taenia, the treatment of tooth ache.

6. Dried leaves are smoked in pipe as core of cough.

7. C. procera is used for digestion.

8. Oil of leaves is useful in skin eruption.

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44.

Received on 03.09.2011

Accepted on 11.09.2011

Research Journal of Pharmacognosy and Phytochemistry. 3(6): Nov. - Dec. 2011, 256-260

Arvind R. Umarkar*, Sunilkumar R. Bavaskar, Yogesh M. Bagad, Shashikant D. Barhate, Ranjit Jadhav and Aakash Makwana.