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AN OVERVIEW OF PHYTOCHEMICAL AND PHARMACOLOGICAL ACTIVITIES

OF CALOTROPIS PROCERA

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 REVIEW ARTICLE
ISSN 2278 – 2818

AN OVERVIEW OF PHYTOCHEMICAL AND PHARMACOLOGICAL ACTIVITIES OF

CALOTROPIS PROCERA

Pusapati Madan Ranjit†, Eswara Rao G., Krishnapriya M., Nagalakshmi V., Silpa P., and Anjali M.
ABSTRACT

Calotropis procera (Ait.) R.Br. has long been used in traditional medicines. Pharmacological studies have revealed that aqueous and organic extracts of
various parts of Calotropis procera and its phytoconstituents such as cardenolides, terpenes, flavonoids enzymes and other chemical constituents
possess a wide range of pharmacological activities such as cytotoxic, antidiabetic, antioxidant, analgesic, anti-inflammatory, antiarthritic, anthelmintic,
antimicrobial, wound healing, anticonvulsant, hepatoprotective, myocardial infarction and immune responses. UNBS1450 is a chemically modified form
of 2-oxovoruscharin, a derivative of voruscharin compound was identified by unibioscreen in the root bark of a plant Calotropis procera. It showed to
have promising anti-cancer potentials. The improved hemi-synthetic compound UNBS1450 is to be significantly less toxic when compared to its mother
compound. It is under Phase 1 clinical trials. The presented review summarizes the information about the phytochemical and pharmacological activities
of the Calotropis procera.

KEYWORDS: Calotropis procera, Phytochemistry, Pharmacological activities.

INTRODUCTION Phytochemical Constituents

Calotropis procera (Ait.) R.Br. of family Asclepiadaceae is a tropical plant
growing wild in warm climate up to an altitude of about 1050 meters. The
plant is distributed throughout India, particularly abundant in Rajasthan.
It also occurs in Pakistan, Africa, Mexico, Australia, Egypt, Central and
South America and Caribbean islands (Anonymous, 1982). The plant is
popularly known because it produces large quantity of latex, which is
easily collected from its green parts when the plant is wounded. The
abundance of latex in the green parts of the plant reinforces the idea that
it is produced and accumulated as a defense strategy against organisms
such as virus, fungi, and insects (Larhsini et al., 1997; Haque et al., 2000).
It is widely used in the Sudanese medicinal system (Ayoub and Kingston,
1981; Ayoub and Svendsen, 1981), Unani system of medicine (Anderson,
1988) and Arabic medicine system (Abulfatih, 1987).
The plant has been widely used in the traditional system of medicine for
the treatment of various ailments. It has been used as a purgative,
anthelmintic, digestive, stomachic, emetic, expectorant, sedative, blood
purifier, an antidote for snake poisoning and for the treatment of ulcers,
tumors, leprosy, asthma, boils, dysentery, eczema, piles, diseases of liver,
and spleen disorders (Kirtikar and Basu, 1935; Nadkarni and Nadkarni,
1960).
A number of ethanomedicinal uses of C. procerea were reported. Whole
plant was used either alone or with other herbs to treat common diseases
such as fever, rheumatism, indigestion, cold, eczema and diarrohea
(Kew,1985), paste of root bark was locally applied in the treatment of
elephantiasis (Chopra et al., 1983), and Root bark powder was used to
treat diarrhea and dysentery and it is an excellent substitute for ipecac.
Traditionally it was used to treat cholera, extracting guinea worms and
indigestion (Jain et al., 1985).
The dried powered leaves can be dusted over wounds, ulcers and old
sores to prompt healing (Abdullah, 1975; Awan et al., 1986). Calotropin
isolated from latex is used as a remedy for Black scars on face; boils, cold,
cough, asthma, ear ache, eczema, skin eruptions, inflammatory lesions,
pain of the body, rheumatism, syphilis, leprosy and oedema (Misra and
Fridowick, 1972). Milky latex is locally applied in the treatment of
cutaneous diseases such as ringworm, syphilitic sores and leprosy (Kew,
1985). Extracts of Calotorpis procera flower was investigated for
Cytotoxicity of human colorectal carcinoma cell line and displayed the
strong cytotoxic activity (Smith et al., 1995).
The various parts of the plant viz., flowers, stem, leaves, roots and the
milky latex are used in various indigenous systems of medicine around
the world and popular among the various ethnic groups in India for the
treatment of variety of ailments. Considerable efforts have been made by
the researchers to justify its efficacy as a curative agent through
pharmacological investigations. The objective of present review is to
highlight the various phytochemical and pharmacological investigations
of this plant.
Phytochemical studies on C.procera have revealed the several types of
compounds were obtained from various parts of the plant and latex of
plant. Table: 1 show the list of chemical constituents such as cardenolides,
triterpeinoids, resins, proteolytic enzymes, flavonoids, tannins, sterol, and
terpenes isolated from C. procera.
Pharmacological Activities
Cytotoxic activities
Dry latex (DL) of Calotropis procera inhibits the growth of roots and
mitotic activity of Allium cepa tip meristem in a dose-dependent manner.
This model evaluates the cytotoxic and anti-mitotic activities of latex of C.
procera and demonstrated that, latex exhibits cytotoxic properties like
standard anticancer drugs such as podophyllotoxin and
cyclophosphamide. However, the mechanism for such an effect needs
further evaluation (Sehgal et al., 2006).
Another study reported that, X15-myc transgenic mice treated with DL
(400mg/kg) for a period of 15 week, protected mice from malignant
changes occurring in liver while sinusoidal architecture and cellular
integrity were slightly disrupted as compared to normal and hydropic
changes were observed. DL produced a significant decrease in the serum
vascular endothelial growth factor (VEGF) levels of X15-myc transgenic
mice from 12.18 ± 0.64 µg/L to 9.75±0.27 µg/L (P =0.002) while the level
of VEGF in normal mice was 7.00±0.55 µg/L. The methanolic extract (ME)
of DL was induced cell death in cell lines viz., Huh-7 and COS-1 cells. It
was evaluated by using tetrazolium (MTT) assay. The ME was subjected
to silica gel G step column chromatography using a combination of non-
polar and polar solvents and 11 fractions were obtained. Out of 11
fractions, fraction 8 exhibited potent cytotoxic effect on both the cell lines.
However, a marginal effect on the killing of non-cancerous cell lines
suggested a high degree of selectivity for transformed cells. Such
differential killing of cancerous cells could relate to their altered
metabolic status and/or membrane properties. The cytotoxic effect of DL
was accompanied by intracellular fragmentation of target cell DNA
observed (Choedon et al, 2006).
The stem organic extracts of C. procera was evaluated against sea urchin
egg development for anti-mitotic activity and for in vivo antiproliferative
activity in mice bearing Sarcoma 180 tumor. Among the five extracts
(hexane, dichloromethane, ethyl acetate, acetone and methanol), ethyl
acetate and acetone extracts displayed higher cytotoxic potential against
tumor cells, with IC50 ranging from 0.8 to 4.4 μg/mL, while methanolic
extract was weakly cytotoxic. Cytotoxic extracts also exhibited cell
division inhibition capacity by antimitotic assay, revealing IC 50 values
lower than 5μg/mL. In the in vivo antitumor assessments, ethyl acetate-
and acetone-treated animals showed tumor growth inhibition ratios of
64.3% and 53.1%, respectively, with reversible toxic effects on liver and
kidneys (Hemerson et al., 2010).

NRI College of Pharmacy, Pothavarappadu Village, Agiripalli Mandal, Krishna District, A.P,
India.†Corresponding author: madanranjit@gmail.com

FS J Pharm Res | 2012 | Vol 1 | No 2 18 Pusapati et al.

Smith et al reported that root extract of plant has been found to produce a
strong cytotoxic effect on COLO 320 tumor cells. (Smit et al., 1995).
Ranjani et alreported that, methanolic, hexane ethyl acetate and aqueous
extracts of roots were tested against Hep2 cancer cells and cellular
proliferation activities assays by MTT colorimetry. Morphological changes
of cancer cell were observed under inverted microscope and cell cycle
parameters were determined by flow cytometry following propidium
iodide staining. All the extracts at various doses of 1,5,10 and 25μg/ml
revealed cytotoxicity except aqueous extract. Ethylacetate extract
(10μg/ml) showed strongest cytotoxic effect (96.3%) on Hep2 at 48 th hr
following treatment, where as methanolic extract and hexane extract
showed cytotoxicity of 72.7% and 60.5% respectively. Extract treated
cells exhibited typical morphological changes of apoptosis and flow
cytometric analysis clearly demonstrated that root extracts initiated
apoptosis of Hep2 cells through cell cycle arrest at S phase, thus
preventing cells from entering G2/M phase. The study indicated that, root
extracts inhibited the proliferation of Hep2 cell via apoptotic and cell
cycle disruption based mechanisms (Ranjani Mathur, et al., 2009).
Another study reported that, antiproliferative activity of alcoholic, hydro-
aqueous, aqueous and their fractions from the roots part of plant using
human oral (kB) and central nervous system (SNB- 78) cancer cell lines,
and the percentage of cell viability was evaluated by the sulforhodamine-
B (SRB) assay. Out of the three extracts of C. procera, alcoholic extract has
shown greater potential for growth inhibition followed by hydro-aqueous
extract at three different concentrations of 10μg/ml, 30μg/ml, and
100μg/ml in dose-dependent manner, where as aqueous extract was
found to be least active against both oral and CNS (Central nervous
system) human cancer lines. Both chloroform fraction of alcoholic extract
and n-butanol fraction of alcoholic extract were found to be
antiproliferative against oral (KB) cancer line and CNS cancer cell line
respectively (Madulika Bhagat et al., 2010) and various studies have
reported that root bark of C. procera has shown high in-vivo tolerance of
tumor growth and prolonged survival in the human xenograft models of
nude mice. (Van Quaquebeke et al., 2005).
Antioxidant and Antidiabetic activity
Dry latex of C. procera was evaluated for its antioxidant and anti-
hyperglycemic effects against alloxan-induced diabetes in rats. Daily oral
administration of DL at 100 and 400 mg/kg doses produced a dose-
dependent decrease in the blood glucose and increase in the hepatic
glycogen content. DL also prevented the loss of body weight in diabetic
rats and brought down the daily water consumption to values comparable
to normal rats. DL also produced an increase in the hepatic levels of the
endogenous antioxidants, namely superoxide dismutase (SOD), catalase
and glutathione, while it brought down the levels of thiobarbituric acid-
reactive substances (TBARS) in alloxan-induced diabetic rats. The efficacy
of DL as an antioxidant and as an anti-diabetic agent was found
comparable to the standard antidiabetic drug, glibenclamide (Roy et al.,
2005).
The antioxidant potential of the methanolic extract of leaves of C. procera
was determined on the basis of their scavenging activity of the stable 1, 1-
diphenyl-2-picryl hydrazyl (DPPH) free radical. IC50 of the methanol
extract showed a strong antioxidant activity of the plant. However the
aqueous extract also showed mild antioxidant activity (Mst Nazma
Yesmin et al., 2008).
Antipyretic activity
The ethanolic extract of the aerial parts, aqueous extract of flowers and
aqueous solution of the dry latex of C.procera showed significant
antipyretic activity in animal models that was comparable to aspirin
(Dewan et al., 2000a; Larshini et al., 2002).
Antinociceptive activity
The various parts of C. Procera plant, viz. roots, aerial parts and latex have
been evaluated for analgesic activity. The ethanolic extract of aerial parts,
chloroform extract of roots and the aqueous solution of dried latex were
tested in acetic acid induced writhing model and exhibited significant
analgesic activity. The ethanolic extract of flowers of the plant was found
to possess a weak analgesic activity (Basu and Chaudhari, 1991). Another
study reported that analgesic activity of latex powder, when administered
orally significantly reduced the writhing induced by acetic acid. This
effect was more pronounced when compared to pre-treatment with
FS J Pharm Res | Vol 1 | No 2
aspirn (Dewan et al., 2000b; Kumar et al., 2000). Chloroform fraction of
root extract showed potential analgesic properties acetic acid in rats
(Basu et al., 1991).
Nociceptive activity of latex protein has been reported using different
pharmacological tests in mice, such as contortions induced by acetic acid,
formalin test and hot plate, as the results showed that the analgesic
properties appear to be independent of opioid system (Soares et al.,
2005).
Inflammatory activity and Anti-inflammatory activity
The milky white latex of plant produces inflammation of the skin and
mucous membranes on accidental exposure. It produces edema on local
administration due to the release of histamine and prostaglandins and is
associated with dermatitis, keratitis, and toxic iridocyclitis (Handa et al.,
1984; Al-Mezaine et al., 2005; Biedner et al., 1977). The acute
inflammation induced by latex involves edema formation and cellular
infiltration that has been attributed to the presence of histamine in the
latex and the release of mast cell histamine (Singh et al., 2000; Shivkar et
al., 2003).The inflammation produced by latex has been demonstrated in
different experimental models of inflammation such as paw edema air bag
(Shivkar et al., 2003), and pleurisy in rats (Singh et al., 2000). Thus, the
latex is a potent phlogistic agent useful for evaluation of new anti-
inflammatory drugs, and also the anti-inflammatory property of the latex
was studied on carrageenin and formalin-induced rat pawoedema model.
A single dose of the aqueous suspension of the dried latex was effective to
a significant level against the acute inflammatory response (Kumar and
Basu, 1994). The crude dry latex possesses a potent anti-inflammatory
activity. The petroleum ether, acetone, methanol and aqueous extracts of
dry latex were tested in the carrageenan induced rat paw oedema model.
All the fractions exhibited anti-inflammatory activity but inhibition of
oedema was found to be greatest with the acetone and aqueous extracts
(Majumdar and Kumar, 1997).
Arya and Kumar et al reported that, the efficacy of extracts prepared from
the latex of C procera was evaluated against inflammation induced by
histamine, serotonin, compound 48/80, bradykinin (BK), and
prostaglandin E2 (PGE2) in the rat paw oedema model. The inhibitory
effect of the extracts was also evaluated against cellular influx induced by
carrageenan. The anti-inflammatory effect of aqueous and methanolic
extracts of DL was more pronounced than phenylbutazone (PBZ) against
carrageenan while it was comparable to chlorpheniramine and PBZ
against histamine and PGE2, respectively. Both extracts produced
inhibition of inflammation induced by BK, compound 48/80, and
serotonin. The histological analysis revealed that the extracts were more
potent than PBZ in inhibiting cellular infiltration and subcutaneous
oedema induced by carrageenan. The extracts of DL exerted their anti-
inflammatory effects mainly by inhibiting histamine and BK and partly by
inhibiting PGE2 (Arya and Kumar, 2005). A chloroform-soluble fraction
ofroots also showed significant dose-related anti-inflammatory activity in
rats (Basu and Nag, 1991). Those results indicated that it has both
inflammatory and anti-inflammatory properties.
Antiarthritic activity
The methanol extract (ML) of dry latex was showed protection against
inflammation and oxidative stress in monoarthritis induced by Freund’s
complete adjuvant (FCA) in rats. Daily treatment of rats with ML (50 and
500 mg/kg) and standard anti-inflammatory drug rofecoxib (20 and 100
mg/kg), produced a significant attenuation in the inflammatory response
and ameliorated the arthritic changes in the joint. The protection afforded
by ML and rofecoxib was more pronounced than that of phenylbutazone
and was associated with normalization of the levels of inflammatory
mediators and biochemical parameters of oxidative stress. However, the
overall protection afforded by rofecoxib was better than that of ML
(Kumar and Roy, 2007).
19 Pusapati et al.
Table 1. Shows the list of chemical constituents were isolated from C.
procera
Part of the plant Chemical class Chemical constituent References
Latex of the plant Cardenolides Calotropin (1) Chopra et al.(1956), Baquar et al.(1984)
Rastogi et al. (1993) Grieve et al (1994)
Calotoxin (2) ‘’
Calactin (3) ‘’
Uscharin (4) ‘’
Voruscharin (5) ‘’
Uzarigenin (6) ‘'
Syriogenin (7) ‘’
Proceroside (8) ‘’
Calotropagenin (9) ‘'

Enzymes A nontoxic proteolytic enzyme:

Calotropain Shukla et al. (1961)
Calotropin DI and DII Rastogi et al. (1993)
Calotropain FI and FII ‘’
An enzyme with invertase activity: ‘’
Trypsin ‘’

Terpenes β-amyrin (10) ‘’

Lupeol (11) ‘’
Taraxast-20(30)-en-3(4-methyl 3-pentenoate) ‘’

Flavonoid Quercetin-3- rutinoside (12) Dubey et al. (2003)

Other constituents α- and β-calotropeols ‘’

3-epimoretenol ‘’
Procerain ‘’
Histamine Shivkar et al. (2003)

α-Amyrin (13) Bryce et al. (1967)

Leaves α-Amyrin acetate (14) Martin- Smith et al. (1967)
β-sitosterol (15) Osman et al.(1975) and Robinstan (1976)
Urosolic acid (16) Mezzetti et al. (1971) and Huneck et al. (1971)
Calotropin (1) Yelne et al. (2000)
Calotropagenin (9) Singh et al. (1972)
Procesterol (A new steroidal hydroxyl ketone) (17) Khan et al. (1989)
Calotropenylacetate (18)
Multiflorenol (19) Yogesh Murti et al. (2011)
16-α-Hydroxy calotropagenin (20) ‘’
O-Pyrocatechuic acid (21) ‘’
‘’
Quercetin-3-rutinoside (12)
Flowers Flavonoid With D-arabinose, glucose, glucosamine Chatterjee et al. (1995)
Polysaccharides and L-rhamnose Atef et al. (1999)
3-Proteinase
Enzymes Calotropain (protease) ‘’
‘’
Lupeol(11) ‘’
Other constituents Uscharin (4) ‘’
Proceroside (8) ‘’
Proceragenin(cardenolide) (22) ‘’
Syriogenin (7) ‘’
Taraxast-20(30)-en-3-(4-methyl-3 pentenoate)3 ‘’
thiazoline ‘’
Cardenolide ‘’
Gigantin ‘’
Giganteol ‘’
Isogiganteol ‘’
Uscharidin (23) ‘’
Uzarigenin (6) ‘’
Voruscharin (5) ‘’
α-calotropeol ‘’
3-epimoretenol ‘’
α- lactuceryl acetate ‘’
α-lactuceryl isovalerate ‘’
‘’
5-hydroxy-3, 7- dimethoxyflavone-4’-O-β-
Roots glucopyranoside (24) Kamel et al. (2010)
2β, 19-epoxy- 3β, 14β-dihydroxy-19-methoxy-5α-
card-20(22)-enolide (25) ‘’
β- ahydroepidigitoxigenin3β-O-glucopyranoside
(26) ‘’
Caroglaucigenin (27)
Seeds Frugoside (28) Rajagopalan et al. (1955)
Carotoxigenine (29) ‘’
Calotropin (1) ‘’
‘’

FS J Pharm Res | 2012 | Vol 1 | No 2 20 www.fonscientia.com/jpharmres

Hepatoprotective activity
Hydro-ethanolic extract (70%) of C. procera flowers was prepared and
tested for its hepatoprotective effect against paracetamol-induced
hepatitis in rats. Treatment with hydro-ethanolic extract of flowers (200
mg/kg and 400 mg/kg) has brought back the altered levels of biochemical
markers such as serum glutamate pyruvate transaminase (SGPT), serum
glutamate oxaloacetic transaminase (SGOT), Alkaline phosphatase (ALP),
bilirubin, cholesterol, high density lipoproteins (HDL) and tissue
glutathione (GSH) to near normal levels at the dose dependent manner
(Setty et al., 2007). The latex was evaluated for its hepatoprotective effect
against carbon tetrachloride (CCl4) induced hepatotoxicity in rats.
Subcutaneous injection of CCl4, administered twice a week, produced a
marked elevation in the serum levels of aspartate transaminase (AST),
alanine transaminase (ALT) and tumor necrosis factor alpha (TNF-α).
Histological analysis of the liver of these rats revealed marked
necroinflammatory changes that were associated with increase in the
levels of TBARS, PGE2 and catalase and decrease in the levels of GSH,
superoxide dismutase (SOD) and glutathione peroxidase (GPx). Daily oral
administration of aqueous suspension of DL of C. procera at 5, 50 and 100
mg/ kg doses produced a dose-dependent reduction in the serum levels of
liver enzymes and inflammatory mediators and attenuated the
necroinflammatory changes in the liver (Padhy et al., 2007). Basu et
al.(1992) evaluated hepatoprotective activity of chloroform extract of
roots of C.procera against CCl4 induced liver injury and found to possess
significant protective activity. The ethanolic (70%) extract of flowers
against CCL4 induced hepatic injury in albino rats and mice. Extract
showed significant hepatoprotective property (Absar et al., 2007).
Anthelmintic activity
The latex of planthas been shown to possess anthelmintic activity against
Haemonchus contortus infection in Najdi sheep. Inappetence, dullness,
erosive abomasitis, decreased haemoglobin concentration and increased
eosinophils were the main features of haemonchosis in the sheep. In the
sheep treated with single oral doses of 0.01 ml and 0.02 ml/ kg body
weight of C.procera latex, it significantly decreased the egg production
and fewer adult Haemonchus worms were found in the abomasum.
Although the appetite improved, the hemoglobin concentration and
serum copper, iron and zinc levels were still reduced after therapy with
Calotropis latex (Al-Qarawi et al., 2001).
Both fresh and aqueous extract of latex of C. procera exhibited a dose-
dependent inhibition of spontaneous motility and evoked responses to
pin-prick. With higher doses (100 mg/ml of aqueous extract and 100 %
fresh latex) the effects were comparable with that of 3 % piperazine. The
study suggested that it might be effective against parasitic infections of
both animals and humans caused by Ostertagia, Nematodirus,
Dictyocaulis, Taenia, Ascaris and Fasciola (Shivkar and Kumar, 2003).
Other In vitro studies revealed anthelmintic effects (P < 0.05) of crude
aqueous extract and crude methanolic extracts of Calotropis procera
flowers on live Haemonchus (H.) contortus as evident from their mortality
or temporary paralysis. For in vivo studies, Calotropis procera flowers
were administered as crude powder (CP), crude aqueous extract and
crude methanolic extracts to sheep naturally infected with mixed species
of gastrointestinal Nematodes. Egg count percent reduction (ECR) was
recorded as 88.4% and 77.8% in sheep treated with crude aqueous (CAE)
and CP at 3 g kg-1 body weight on day 7 and 10 post-treatment (PT)
respectively. Crude aqueous extract was least effective resulting in 20.9%
reduction in ECR on day 7 PT. It was found that C. procera flowers possess
good anthelmintic activity against nematodes (Iqbal et al., 2005).
Antimalarial activity
The traditional use of latex is given in malarial and low hectic fevers
(Khory and Katrak, 1981). Sharma and Sharma screened the ethanolic
extracts of C.procera leaves, stems, roots, flowers and flower buds, for
their in vitro antimalarial activity against a chloroquine (CQ) sensitive
strain, MRC 20 and a chloroquine resistant strain, MRC 76 of Plasmodium
falciparum using the Desjardins method and the effectiveness of its
fractions were compared with the CQ sensitive strain than the CQ
resistant strain (Sharma and Sharma, 2000a and Sharma and Shrama,
2000b). In further investigation, in vitro hemolysis of human erythrocytes
has been studied with above extracts. The putative anti-plasmodium
activity of these extracts was correlated to their cytotoxicity as
represented by the in vitro rate of hemolysis (Sharma and Sharma, 2001).
FS J Pharm Res | Vol 1 | No 2
Anticonvulsant activity
Jalalpure reported that the anticonvulsant activity of different root
extracts of Calotropis procera in rats in order to evaluate the traditional
use of this plant. The anticonvulsant activity of different extracts of
C.procera roots was studied against seizures induced by maximal
electroshock seizures (MES), pentylenetetrazol (PTZ), lithium-pilocarpine
and electrical kindling seizures. In the PTZ test, the chloroform extract
showed a highly significant (p < 0.001) effect, whereas the aqueous
extract showed the most significant (p < 0.01) effect as compared to
control by delaying the onset of convulsions. These extracts were also
inhibited convulsions induced by lithium-pilocarpine and electrical
kindling. The results of this study indicated that the chloroform extract
and aqueous extract of C. procera roots may be beneficial in the absence
(petitmal) and tonic clonic (grand mal) type of seizures (Jalapure, 2009).
Effects on reproductive organs
Calotropin(1) was reported as an abortifacient in gerbrils, rabbits and
rats (Gupta et al., 1990). Intramuscular administration of aqueous and
ethanolic extracts of flowers has been shown to induce functional sterility
in mice (Sharma and Jacob, 2001). Akinloye reported the
histomorphometric and histopathological evaluations of the effects of
fresh leaf extract has depicted potential deleterious effect on the testes
and accessory sex organs of male Wistar rats (Akinloye et al., 2002).The
effect of ethanolic extract of the roots of planthas been studied in female
albino rats to explore its antifertility and hormonal activities. A strong
anti-implantation (inhibition 100%) and uterotropic activity was
observed at the dose level of 250 mg/kg (1/4 of LD50). One other study
also reported that ethanolic extract of root exhibited stronger anti-
implantation activity as compared to ethanolic extract of leaves (Kamath
and Rana, 2002). In one study the aqueous and ethanolic extracts of roots
bring about temporary inhibition of ovulation (Circosta et al., 2001).
Spasmolytic activity
The aqueous extract of C. procera was showed spasmolytic effect on
trachea smooth muscle chain of Guinea-pig. The extract (50, 100 and 200
μg/ml) showed a dose dependent relaxant activity probably exhibited
through the direct relaxant action on the smooth muscle (Ezekiel et al.,
2005). Kumar and Shivkar reported the effect of DL on smooth muscles of
gastrointestinal tract. Oral administration of DL to rats (50–1000 mg/kg)
produced a dose-dependent decrease in intestinal transit along with a
decrease in intestinal content as compared to control group. At lower
doses DL produced dose-dependent contractions of gastrointestinal
smooth muscles in vitro (rabbit ileum and fundus of rat stomach) that was
followed by desensitization at higher doses (Kumar and Shivkar, 2004).
Antidiarrhoeal activity
DL produced a decrease in intestinal transit (27–37%) as compared to
both normal and castor oil treated animals. Unlike atropine, DL
significantly inhibited castor oil induced enteropooling. However, it did
not alter the electrolyte concentration in the intestinal fluid as compared
to castor oil treated rats (Kumar et al., 2001).
Antimicrobial activity
The antifugal activities of aqueous extract of stem bark of Calotropics
procera were determined against Epidermophyton flocosumand
Tricophyton gypseumusing agar diffusion techniques. The crude extract of
C. procerashowed activity on E. flocosumand T. gypseumat 4.0 mg/ml. The
result of minimum inhibitory concentration (MIC) was 0.5 and 0.9 mg/ml
and that of minimum fungicidal concentration (MFC) were 2.0 and 4.0
mg/ml, respectively (Kuta, 2008). The antimicrobial effect of ethanol,
aqueous and chloroform extracts of leaf and latex of Calotropis procera on
six bacteria namely, Escherichia coli, Staphylococcus aureus,
Staphylococcus albus, Streptococcus pyogenes, Streptococcus pneumoniae
and three fungi: Aspergillus niger, Aspergillus flavus, Microsporium
boulardii and one yeast Candida albicans was determined using agar well
diffusion and paper disk methods.
The results revealed that ethanol was the best extractive solvent for
antimicrobial properties of leaf and latex of C. procera followed in order
by Chloroform and aqueous (P<0.05). The ethanolic extracts of latex gave
21 Pusapati et al.
the widest zone of inhibition (14.1mm) against E.coli using agar well
diffusion while 9.0 mm was recorded for the same organism in the disc
plate method. The growths of six bacterial isolates were inhibited by the
three extracts except P.aeruginosa and S.pyogenes that were not inhibited
by the aqueous extracts of both leaf and latex. Similarly, the growth of
four test fungi were inhibited by ethanol and chloroform extracts while
the aqueous extract was the least effective on the test fungi. The best
antifungal activity was recorded by ethanol extract of latex against
Candida albicans. The minimum inhibitory concentration (MIC) for the
ethanol extract was between 5.0 and 20.0 mg/ml for fungi. This study
revealed that the latex demonstrated strong inhibitory effect on the test
organisms than leaf (Kareem, 2008). Bhaskar reported that Chloroforms
extract of C. procera seeds exhibited better antimicrobial activity
(Bhaskar, 2000). A new cardenolide, proceragenin, screened for its
biological effect showed significant antibacterial activity against both
Gram positive and Gram negative bacteria (Akhtar et al., 1992).

Neuroprotective effective

Alzheimer’s disease (AD) commonly known as dementia is an organic,

progressive, chronic brain disorders characterized by multiple cortical
functions, including memory, orientation, comprehension and language
ability and learning. Powder latex can be used to treat the early symptoms
of dementia of Alzheimer type. Powder latex, had decreased the
deposition of beta-amyloid in mouse brain, and showed a protector and
antioxidant activity in this organ (Joshi et al., 2008).

Immune responses activity

Abdel latif Shaker et al reported that the aqueous extract of latex

enhances nitric oxide synthase (iNOS) gene expression and NO
production in murine macrophages, proving the ability of extract to
activate the effector cells in inflammatory and immune responses. This is
an important observation because it reveals one of the mechanisms
underlying the wide range of pharmacological actions of C.procera (Abdel
latif Shaker et al., 2009).

FS J Pharm Res | 2012 | Vol 1 | No 2 22 www.fonscientia.com/jpharmres

 CONCLUSION

Based on the many ethanomedicinal remedies of this plant, is useful for

find to increasing applications as source of direct therapeutic agents,
models for new synthetic compounds and as taxonomic marker for the
discovery of new compounds. Research on phytochemical composition of
this plant exhibited the presence of various active principles. Van
Quaquebeke et al. (2005) isolated a natural cardio tonic steroid from the
methanolic extract of C. procera root barks called 2’’-oxovoruscharin
(UNBS1244) and developed a new hemisynthetic cardenolide derivative
named UNBS1450 (30). It is a potent source of in vivo antitumor activity
in the case of paclitaxel and oxaliplatin-resistant subcutaneous human
NCIH727 and orthotopic A549 xenografts in nude mice. UNBS1450 could
constitute a potential weapon against human experimental NSCLCs.
UNBS1450 is able to deactivate highly activated NF-nB pathways in A549
NSCLC cells by acting simultaneously at several points along this pathway
as well as by down-regulating c-Myc in cancer cells. (Mijatovic et al., 2006;
Mijatovic et al., 2007; Juncker et al., 2009). It also triggers apoptosis by
cleavage of pro-caspases 8, 9 and 3/7, by decreasing expression of anti-
apoptotic Mcl-1 and by recruitment of pro-apoptotic Bak and Bax protein
eventually resulting in cell death (Tom Juncker et al., 2011). Mcl-1 can
cause cancer cells to grow out of control.

According to the reports of PBS-Biotechnology, Dr. Michael Bittner, a

biologist and Principal Investigator of the PBS--‐Bio technology said that
“it is a very nice candidate drug,” it effective against MCL1 in very low
dosages, which means it could potentially be delivered to patients with
minimal side effects and low toxicity.MCL1 is prevalent in leukemia,
non‐small-cell lung cancer, as well as cancers of the prostate and
pancreas. Dr. Edward Smith, co-founder and CEO of PBS-Bio said that,
“The presence of MCL1 can be used as stratification, or predictive,
biomarker to help determine which cancer patients are most likely to
respond to UNBS1450. UNBS1450 has been in phase I clinical trials at
hospitals in Belgium and the Netherlands. Pre-clinical tests showed that
UNBS1450 is very effective against various tumor types with no adverse
side effects (Mesa, 2011). The presence of a number of phytoconstituents,
its wide variety of pharmacological actions C. procerea is a potential
source for the development of new drugs to pharmaceutical industry.
ABBREVIATION
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