indo american journal of pharmaceutical research, … · indo american journal of pharmaceutical...

www.iajpr.com

Page1

739

Indo American Journal of Pharmaceutical Research, 2014 ISSN NO: 2231-6876

Journal home page:

http://www.iajpr.com

INDO AMERICAN

JOURNAL OF

PHARMACEUTICAL

RESEARCH

ASCLEPIAS CURASSAVICA: A REVIEW OF ETHNOMEDICAL, PHYTOCHEMICAL AND

PHARMACOLOGICAL INFORMATION

Raja Sundararajan and Ravindranadh Koduru GITAM Institute of Pharmacy, GITAM University, Visakhapatnam- Andhra Pradesh, India-Pincode-530 045

Corresponding author

Dr. S. Raja,

M.Pharm.PhD, Associate Professor

GITAM Institute of Pharmacy

GITAM University, Gandhi Nagar,

Rushikonda, Visakhapatnam-530 045

Andhra Pradesh, India

+91 9160508261

[email protected]

Copy right © 2014 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical

Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ARTICLE INFO ABSTRACT

Article history

Received 29/03/2014

Available online

16/04/2014

Keywords

Asclepias Curassavica,

Acesodyne,

Cardenolides,

Expectorant,

Homeostasis.

The current review describes the morphological, phytochemical and ethnopharmacological

aspects of Asclepias curassavica L. (Asclepiadaceae). Asclepias curassavica has been known

since ancient times for its curative properties and has been utilized for the treatment of

various ailments such as tumor, asthma, fever, homeostasis, inflammation, diarrhoea,

catharitic, emetic, expectorant, warts, and acesodyne. In recent decades, a great number of

chemical and pharmacological studies have been done on Asclepias curassavica. This

contribution provides a comprehensive review of the pharmacologically relevant compounds

of Asclepias curassavica characterized so far and of the studies supporting its use as a

medicinal plant. Particular attention has been given to cardiovascular, cytotoxicity, urinary

stimulatory, antifertility, antiviral, antifungal, anticrustacean, insecticidal, antiamoebic, anti-

inflammatory, anticoagulatory, antioxidant and antibacterial effects. Several chemical

constituents including cardenolides, flavanols, phenols, aliphatic, alicyclic compounds and

alkaloids were present in this plant. The present outcome of review summarizes the most

interesting findings related to the traditional and folkloric uses, phytoconstituents and

pharmacological aspects of Asclepias curassavica.

Please cite this article in press as Dr. S. Raja, et al. Asclepias Curassavica: A Review of Ethnomedical, Phytochemical and

Pharmacological Information. Indo American Journal Of Pharm Research.2014:4(04).

http://www.iajpr.com/index.php/en/

www.iajpr.com

Page1

740

Vol 4, Issue 04, 2014. Dr. S. Raja, et. al. ISSN NO: 2231-6876

INTRODUCTION

Medicinal plants are the plants whose extracts can be used directly or indirectly for the treatment of different ailments.

Medicinal plants are an integral component of ethnoveterinary medicine. Medicinal plants, since times immemorial, have been used in

virtually all cultures as a source of medicine. Herbs have always been the principal form of medicine in India and presently they are

becoming popular throughout the developed world. [1]. An increasing reliance on the use of medicinal plants in the industrialized

societies has been traced to the extraction and development of several drugs and chemotherapeutics from these plants as well as from

traditionally used rural herbal remedies. The plants belonging to the Asclepiadaceae family has very high medicinal property.

Asclepias curassavica is one such plant which comes under Asclepiadaceae family. The plant is used medicinally in the tropics for the

anodyne properties of its roots. Asclepias curassavica is commonly called as milk weed. Taxonomical classification and other

common names of this plant were mentioned in below Table 1 and Table 2 respectively [2].

Table 1: Taxonomical classification of Asclepias curassavica

Taxonomical classification

Kingdom Plantae

Division Angiosperms

Order Gentianales

Family Asclepiadaceae

Genus Asclepias

Species curassavica

Table 2: Common names of Asclepias curassavica

Common names

English Bastard ipecac, Blood flower, Blood flower milkweed, Butterfly weed, False ipecac, Milkweed,

Red cotton bush

Fijian

False ipiciachuana, Vu Ni Lolia, Wathiwathi

French Herbe À Gendarme, Ipéca sauvage

Hawaiian Lauhele, Laulele, Nu„Umela, Pua „Anuhe

Hindi Madhar

Maori (Cook

Islands)

Tirika

Marshallese Ialo, Kabbok

Samoan Pepe Toa, Pepetoa, Vao Fualele, Vaomumu

Spanish

Algodoncillo, Caballo, Corcalito, Flor De Sangre, Yuquillo

Tahitian Tirita

Tongan Lou Pepe, Tu„Ulapepe, Vavae Kona

Morphology

The milkweed has a white, poisonous sap from which it gets its name, and can grow to be 2 to 3 ½ feet. Erect branched herb

to 1.5 m tall; leaves opposite, oblong-lanceolate, acute at both ends, 6-15 cm long, 1-3 cm wide; cymes on peduncles 3-6 cm long, 4-

15-flowered; flowers bright red-and yellow; calyx-lobes to 4mm long; corolla to 9 mm long; corona-scales to 4mm long; stamen-tube

to 3 mm long; follicles ovoid-oblong, 5-7.5 cm long; [2]. The seeds, which grow in a pod, have a silky tuft of hair which allows them

to be blown by the wind like little parachutes. It attracts bees, butterflies, and hummingbirds. Monarch butterflies particularly like it,

just like butterfly weed, which is in the same family. Milkweed is the flower of choice for Monarchs in North America. It was an all-

purpose remedy for Native Americans. It requires poor sandy disturbed soils, but produce more and larger clumps of flowers when

watered and planted in improved soil. Milkweed is a native plant of the South American grasslands. It can be found in southern

Canada, and the central United States, but its favourite place to grow is South America. The above mentioned plant morphological

features were illustrated in Table 3.

http://en.wikipedia.org/wiki/Plant

http://en.wikipedia.org/wiki/Flowering_plant

http://en.wikipedia.org/wiki/Gentianales

http://en.wikipedia.org/wiki/Asclepiadaceae

www.iajpr.com

Page1

741


Table 3: Morphological features of Asclepias curassavica

Morphological features

Bloom time Spring-late Fall

Flowers Five-petaled flowers in clusters, white, greenish, yellow, or orange depending on species. Long blooming season

usually from spring through fall.

Fruit Pods, which split open when ripe allowing fluffy seeds to be distributed by the wind.

Height 1 to 3 feet

Leaves Oval, lance-shaped, or long and narrow; stems usually have a milky sap

Light

Requirements

Full sun to part shade.

Mass spread 1 to 2 feet planting

Origin Native to North America

Plant type herbaceous; annual

Soil requirements Usually found on poor sandy disturbed soils, but produce more and larger

Clumps of flowers when watered and planted in improved soil.

Water

Requirements

Drought resistant once established.

Zones 5-11

Habitat

In Hawaii, "naturalized in low elevation, often dry habitats" [3]. In Fiji, "seen as a coarse herb to 1.5 m high from near sea

level to about 900m, locally frequent along roadsides, in open fields, and in coconut plantations" [4]. Occasional as a weed,

particularly in pastures [5]. In New Guinea,"a weed of roadsides, waste land and pastures, also in grassland, particularly in savannahs.

From low altitudes to 1500m; most often in areas of seasonal climate" [6]. In Tonga, "a common waste-area weed" [7].

ETHNOMEDICAL INFORMATION ON ASCLEPIAS CURASSAVICA

Various literatures have demonstrated numerous ethnomedical uses of Asclepias curassavica in different countries. As per

the published reports, different parts of the plant have got different ethnomedicinal indications worldwide, which have been stated

below (Table 4).

India

In India, the hot water extract of entire plant is used as a fish poison, cathartic (humans), and emetic [8]. The fresh petals are

used as eye drops for chronic eye diseases [9]. The root was used as an emetic [10] and anti diarrhoeal agent. The plant is also

reported to be used as a poultice for ringworm [11]. The hot water extract of dried leaves are used as an anthelmintic [12].

Peru

The dried aerial part of the plant is used for the treatment of nasopharyngeal cancer, tumors and warts [13]. The latex part of

the plant is used for a variety of diseases, such as decayed teeth, anthelmintic and rat poison. Leaves of the plant are used traditionally

to treat diarrhoea, wounds and fever [10]. The hot water extracts of dried leaf and stem are considered as expectorant, vomitive,

diuretic, cicatriazant and anthelmintic [14].

Nicaragua

The entire plant of Asclepias curassavica is used in the treatment of worms, intestinal parasites and diarrhoea [15]. The parts

of leaf and stem are used to treat asthma [16].

Mexico

The entire plant is used traditionally to treat head cold and intestinal parasites [17, 18]. The latex and leaf part of the plant

were indicated to cure warts and wounds [19]. It is also recommended to treat pain in molars [18], pimples and hemorrhoids [20]. The

fresh latex part of the plant has been reported to be used for malaria and vermifuge [21]. In addition, the dried sap of plant was

traditionally prescribed as purgative [17]. Hot water extract of dried stem of plant was used for asthma [21]. It is also used to treat gall

bladder aches [18].

West Indies

The entire plant is used in folk medicine as a vermifuge. Dried flowers and leaves are most frequently used for applying on

wounds to enhance the healing process [22].

Brazil

In Brazil, several ethnic groups cultivate Asclepiascurassavica and used to control ticks for humans [23]. In the rural area of

Brazil, the fresh latex of plant is used in folk medicine as a remedy for cardiac problem, emetic and purgative [23]. The aerial part of

www.iajpr.com

Page1

742


the plant was used to control ticks in cattle [24]. Dried root decoction of the plant was used as febrifuge, vermifuge and in the

treatment of gonorrhea and asthma [23].

Iran

The fresh leaf of the plant is used as anthelmintic and to stop bleeding. The dried root is also used for several diseases like

haemorrhoids, urinary tract inflammation, emetic, laxative, astringent and vaginally in leucorrhoea. The fresh exudates of the plant

were used on corns [22].

Guatemala

The leaf twigs are used for gonorrhoea [25].

Nepal

The juice of leaf is reported to be used for boils [26]. The juice from root and fresh leaf is used as an anthelmintic [27].

Table 4: Ethnomedical Information of Asclepias curassavica

Parts of Plant Route of administration/Type

of extract

Uses References

Dried aerial part external /Infusion

used for nasopharyngeal cancer, tumours and warts (human

adult)

[13]

Bark

oral /decoction

used for diarrhea (human adult)

[15]

used for worms.

(human adult)

used for intestinal parasites (human adult)

Entire plant.

Not mentioned used as a fish poison

[8]

oral/ hot water extract

used as a cathartic

(human adult)

used as an emetic (human adult)

oral/ infusion used to treat intestinal parasites (human adult) [17]

external/ decoction used to treat head colds (human adult ) [18]

Dried entire

plant

external/ decoction used for pimples (human adult) [20]

oral/ decoction used for hemorrhoids(human adult)

oral/decoction

used for diarrhea (human adult)

[15] used for worms and intestinal parasites

Fresh entire

plant

external/decoction

external/decoction

used to control ticks (human adult) [23]

Fresh exudates used on corns

human adult

[22]

Dried flower +

leaf

applied on wounds to enhance the healing process (human

adult)

Latex(leaf)

used for warts

( human adult)

[19]

used for wounds (human adult)

Dried latex

(leaf)

used to treat pain in molars. The leaf's latex is placed over the

affected molar (human adult)

[18]

Latex

oral/ extract type not stated

used to extract decayed teeth. (human adult)

[10]

used as an anthelmintic. (human adult)

extract type not stated used as a rat poison.

reported to be cardioactive (human adult).

[23]

used for emetic (human adult).

used as a purgative. (human adult)

www.iajpr.com

Page1

743


Fresh latex oral/decoction used for malaria

(human adult)

[21]

used as a vermifuge

(human adult)

Leaf +stem

route not given used to treat asthma.

(human adult)

[16]

Leaf

oral/ extract type not stated used to treat diarrhea.

(human adult)

[10] external/ extract type not stated used to treat wounds.

(human adult)

external/decoction used to treat fever.

(human adult)

Dried leaf

oral/hot water extract used as an anthelmintic (human adult) [12]

oral/decoction used to treat gall bladder aches (human adult) [18]

Fresh leaf

oral/decoction used as an anthelmintic agent.(human adult)

[22]

external/decoction used to stop bleeding.

Dried leaf +

stem

Dried leaf +

stem

oral/hot water extract

used as an expectorant.(human adult)

[14]

[14]

used as a vomitive

(human adult)

used as a diuretic (human adult)

used as a cardiotonic. (human adult)

Used as an anthelmintic.

external /hot water extract used as a cicatrizant (human adult)

Leaf + twigs oral/ infusion used for gonorrhea (human adult) [25]

Leaf external/leaf juice used for boils (human adult) [26]

Root

oral/decoction

used as an anthelmintic (human adult)

Fresh leaf used as an anthelminthic (human adult) [27]

Aerial external/decoction used to control ticks in cattle. [24]

Part not

Specified

external/ extract type not stated used as a poultice for ringworm (human adult) [11]

Fresh petals

ophthalmic/decoction used as eye drops for chronic eye diseases (human adult) [9]

Root

oral/type ext not stated

used as an emetic (human adult) [10]

used to treat diarrhea (human adult)

Dried root

Dried root

oral/ decoction

used for gonorrhea (human adult)

[23]

used to treat asthma.

(human adult)

used as a vermifuge (human adult)

used as a febrifuge (human adult)

external/ decoction applied for hemorrhoids (human adult)

[22]

oral/ decoction

oral/ decoction

used to reduce urinary tract inflammation (human adult)

used as an emetic

(human adult)

used as a laxative

(human adult)

used for its astringent effect (human adult)

vaginal/decoction applied vaginally in leucorrhea (human adult- female)

www.iajpr.com

Page1

744


PHARMACOLOGICAL ACTIVITIES OF ASCLEPIAS CURASSAVICA

Asclepias curassavica is used for different purposes in traditional medicine around the world; therefore, researchers have

tested it for different types of biological activities (Table 5). Most tests have been performed on crude extracts without examining the

nature of the active compounds. The results of these studies are listed below and include both positive and negative results.

Effect on cardiovascular system

In Egypt, dried flowers, leaf, pericarp, root and seed of the plant have been found to possess preservative effects on

cardiovascular system [28]. The results of studies exhibited that different parts of the plant protected myocardial cells and have

cardiotonic effect. Patnaik and Dhawan [29] investigated the pharmacological effect of asclepin - a new cardenolide from Asclepias

curassavica and described the cardiotonic activity and acute toxicity. 3´-O-acetylcalotropin (asclepin), a new glycoside was evaluated

for its cardiotonic activity both in vitro and in vivo, in cat, guinea pig, dog, monkey, pigeon and mouse. Asclepin showed a marked

positive inotropic effect as evident from the increase in the force of contraction. It was found to be more active than the other

glycosides. A cardiac glycoside, curassavicin, was isolated from the plant [30]. Curassavicin had a digitalis-like effect on frog or

mammalian hearts. When injected into lymph sac, it produced a systolic arrest in frog‟s heart. On mammalian hearts small doses

increased the amplitude but slowed down the heart rate; toxic doses produced arrhythmia and systolic arrest. In the electrocardiogram

of guinea pigs it prolonged the P-R and R-R intervals and caused an inversion of the T-wave. The minimum lethal doses of

curassavicin, the tincture of this plant, digitoxin, and g-strophanthin in pigeons were 0.751 ± 0.017, 549.7 ± 19.4, 0.777 ± 0.029, and

0.170 ± 0.004 mg/kg., respectively. The biological activity of curassavicin was higher than that of digitoxin but lower than that of g-

strophanthin. The degree of accumulation of curassavicin in 24 hrs was less than that of g-strophanthin in pigeons.

Uterine stimulatory effect

The leaf and stem of plant have been used for uterine relaxant effect in female rats [31]. The hot water extract are tested for

the above activity in Jamaica and the concentration was used 33ml/litre. The result showed weak uterine stimulant effect.

Antifertility effects

Antifertility effect was carried out on female albino rats [32]. The leaf and stem parts of plant were extracted with 95%

ethanol. The ethanol extract was administrated orally at the dose of 10gm/kg. The results suggested that hydroalcoholic extract did not

show any significant antifertility activity. The same results also obtained from the extracts of water and petroleum ether.

Antiviral activity

In Belgium, the 80% ethanolic extract of freeze dried entire plant was tested for antiviral activity [33]. The antiviral activity

was tested against Adeno virus, Coxsackie b2, Herpes type-1, Measles, Poliovirus-1 and Semlicki forest virus by cell cultured method.

The results of the study showed that, no antiviral activity against the organisms mentioned.

Anticrustacean activity

The methanolic extract of fresh entire plant of Asclepias curassavica was screened for anticrustacean activity with

Artemiasalina [34]. The results of the preliminary investigation indicated that, 50% inhibition concentration effect.

Antiyeast/antifungal activity

Moulin-Traffort tested the plant for its yeast activity [35]. The plant extract inhibited the growth of Candida albicans.

Further, the plant was tested for antifungal activity [36] against Neurospora crassa and Candida albicans. The plant extract did not

show antifungal activity against organisms mentioned. The antifungal activity tested against the organisms of Cladosporium

cucumerinum (30µg/disc) and Penicilliu moxalicum (30µg/disc) [17]. The plant extract did not show antifungal activity against

organisms mentioned. Asclepias curassavica- latex saps inhibit the growth of Candida albicans because they degrade a great number

of yeasts [35]. This was confirmed by scanning and transmission electron microscopy observations.

Cytotoxic activity

The hydroalcoholic extract of (95%) entire part of the plant was examined for cytotoxic activity [37]. CA-9KB cell line is

used for the studies. The results of the study suggested that, the extract possess strong inhibition effect and ED50 value was found to be

1.3µg/ml. Systemic fractionation of the extract has led to isolation and characterization of calotropin as a cytotoxic principle [37].

Calotropin is similar in structure to two cardiac glycosides recently shown to be responsible for the cytotoxicity. Cardenolides [38]

obtained from the Asclepias curassavica L possessing cytotoxity activity. The results showed that asclepin had the strongest cytotoxic

[22]

Dried sap

oral/decoction

used to treat parasites

(human adult)

[17]

used as a purgative

(human adult)

Dried stem oral/hot water extract used for asthma (human adult) [21]

www.iajpr.com

Page1

745


activity with an IC50 value of 0.02 lM against the two cancer cell lines and the new compound 13 had significant cytotoxic activity

with IC50 values of 0.69 and 1.46 l M, respectively.

Anti-inflammatory activity

Dried aerial part of hydroalcoholic extract (95%) of plant was shown to have the anti-inflammatory activity [39].

Insecticidal activity

Schmeda-Hirschmann and Rojas De Arias, determined the insecticidal activity [24] (Rhodnius neglectus) of petroleum ether

extract of plant. The results of the study indicated that inactive effect.

Antiamoebic activity

The hydro alcoholic extract (95%) of dried sap of plant was used for antiamoebic activity against Entamoeba histolytica [17].

The MIC value was found to be >250 µg/ml.

Antibacterial activity

Hydroalcoholic extract (95%) of plant was investigated for antibacterial activity [40] against four different strains of bacteria

such as, Escheria coli (10ml/gm), Pseudomonas aeruginosa (50 mg/ml), Staphylococcus aureus (50 mg/ml), Aspergillus niger (50

mg/ml) and Bacillus subtilis (50 mg/ml) by zone of inhibition method. The results of the study showed that the extract was ineffective

against the organisms except Bacillus subtilis. The hydroalcoholic extract (95%) and water extracts of dried fruit of plant have been

evaluated for their antibacterial activity against Staphylococcus aureus and Escherichia coli [41]. The extract of dried fruit was

reported to be active against Staphylococcus aureus.

Thrombin like activity

Cysteine proteases from Asclepias curassavica latex exhibited strong pro-coagulant action [42].

Anti-oxidant activity

Different concentrations of different extracts (chloroform, ethyl acetate, methanol and hydro alcohol) of A. curassavica were

investigated for in vitro antioxidant activity using the thiocyanate method. The hydroalcoholic extract exhibited the highest inhibitory

activity on peroxidation, over the other organic extracts, and was subjected to further in vivo antioxidant activity. The IC50 value

(31.2μg/mL) of hydroalcoholic extract was found to be less than the standard, α-tocopherol (IC50 value 66.1μg/mL). The hydro

alcoholic extract significantly (p < 0.05) increased the FRAP on days 7 and 14 of treatment. Significant (p < 0.05) reduction of

TBARS along with an increase in the SOD enzyme level in the liver and kidney at two different doses was observed. Treatment at a

500 mg/kg bodyweight dose caused a significant increase only in the level of CAT in the liver and kidney. However, there was no

significant effect of TBARS, SOD and CAT in the heart, and the GSH level in liver, heart and kidney.

Toxicity studies

The hydroalcoholicextract (1:1) of entire plant was administered to mouse through oral route at doses up to 1000mg/kg and it

was observed that no mortality and no toxicity occurred during the observation period [37]. Administration of extract of dried plant by

i.v. route to pigeon caused toxic effect with a MLD of 549 mg/kg [30]. The fresh latex of the plant was reported to have ocular toxicity

[43]. The fluid extract of Asclepias curassavica (10mg/animal) was tested in rats by i.p route for toxic effect [44]. The animals were

administered with the extract for 10days. At the end of the 5th day, all animals were suffering from diarrhea and were continuously in

tremors. Animals were killed and examined grossly. Petechiae were noted in the hearts of 60% of the animals. The lungs of all

animals were blanched and hemorrhagic. The liver appeared to have very small petechiae and the kidneys of all animals were swollen.

The gastro-intestinal tract was blanched, distended with air and hemorrhagic in all animals. Ovaries, adrenals and pancreas appeared

normal. The fluid extract of plant was also tested for toxic effect at the doses of 5.0mg/animal in rats by i.p route for five days [44].

No death was occurred. Histopathology showed that the heart, lungs, liver, kidneys and endocrine glands were normal in all respects.

The gastrointestinal tract was slightly distended with air. The toxic effect was also investigated for rabbit (i.v route) at the doses of

0.04ml/kg [44]. The dose employed represented about 30mg/kg of dried plant material. The extract produced a state of partial

paralysis almost immediately. Death was caused by respiratory failure and severe convulsive states. Extracts of aerial parts of the plant

produced similar results.

www.iajpr.com

Page1

746


Table 5. Pharmacological activity of Asclepias curassavica

Parts of Plant Type of extract Uses References

Dried aerial

Ethanol extract

(95%)

anti-inflammatory activity [39]

Entire plant

cytotoxic activity (Ca-9kb-

ED50 1.3 g/ml)

[37]

antibacterial activity

(Bacillus subtilis)

[40]


(Escherichia coli)


(Pseudomonas aeruginosa)


(Staphylococcus aureus)

antifungal activity

(Aspergillusniger)

Freeze-dried entire

plant

Ethanol extract

(80%)

antiviral activity

(Virus-adenovirus)

[33]

antiviral activity

(Virus-coxsackie b2)

antiviral activity

(Virus-herpes type 1)

antiviral activity

( Virus-measles)

antiviral activity

(Virus-poliovirus I)

antiviral activity

(Virus-semlicki-forest)

Fresh entire plant Methanol extract anticrustacean activity

(Artemiasalina )

[34]

Oven dried flowers extract type not

stated

cardiotonic activity [28]

Dried fruit

ethanol extract

(95%)



[41]

Curassavicin Not mentiond cardiotonic activity [30]

Latex Ethanol extract

(95%)

antiyeast activity

(Candida albicans)

[35]

Asclepin (cardenolide

from

Asclepiascurassavica)

Not mentioned cardiotonic activity [29]

Dried fruit

Ethanol extract

(95%)


(Escherichia coli)

[41]

water extract


(Escherichia coli)



Fresh latex latex

antiyeast activity

(Candida albicans)

[35]

Oven dried leaf

tincture

cardiotonic activity

[28] Shade dried leaf

Sun dried leaf

Leaf+stem

Ethanol extracts

(95%) (dose 10.0

gm/kg)

antifertility effect

(rat –female)

[32]

petroleum ether

www.iajpr.com

Page1

747


extract (dose 10.0

gm/kg)

hot water extract

(dose 33.0

ml/liter)

uterine relaxation effect (rat –

female)

[31]

Dried part not

specified

petroleum ether

extract ( conc

used 50.0 mcg)

insecticide activity

(Rhodniusneglectus)

[24]

extract type not

stated

antifungal activity

(Neurosporacrassa)

[36]

antifungal activity (Candida

albicans)

Oven dried pericarp

tincture

cardiotonic activity

[28]

Oven dried root

Dried sap

ethanol extract

(95%)

antiamebic activity

(Entamoebahistolytica)

MIC>250 mcg/ml

[17] antifungal activity

(Cladosporiumcucumerinum)

antifungal activity

(Penicilliumoxalicum)

Oven dried seed tincture cardiotonic activity [28]

Calotropin-

(cardenolide from

Asclepiascurassavica)

ethanol extract

(95%)

cytotoxic activity [37]

PHYTOCONSTITUENTS IN ASCLEPIAS CURASSAVICA

Cardenolides

Cardenolide glycosides were isolated from the seeds of Asclepias curassavica [45]. Two cardenolides and twelve glycosides

were obtained from the seeds of Asclepias curassavica. Among these, four compounds were determined to be 16α-

hydroxycalotropagenin, 16α-hydroxycalotropin and its 3'-O-glucoside and 3'-O-gentiobioside. Normally linked triosides of

corotoxigenin, coroglaucigenin and 12β-hydroxycoroglaucigenin were characterized as cellobiosyl-allomethylosides. The

cardenolides of 3'-epi-19-norafroside and 12β-hydroxycoroglaucigenin were isolated from stem part of Asclepias curassavica. The

structures were determined by spectral and chemical methods [46]. Cardenolide derivative of asclepioside 1, asclepioside 2,

asclepioside 3 and asclepioside 4 were identified and isolated from aerial part of the plant [47]. Frugoside and 12-hydroxyfrugoside,

4‟-O celobiosylfrugoside obtained from seed part of Asclepias curassavica [45]. Cardenolides like uscharidin, uscharin, voruscharin

and triterpenes were isolated from stem and latex parts [48-54]. Singh and Rastogi determined the chemical investigation [55] of

Asclepias curassavica. The alcoholic extract of the plant exhibits strong cardiotonic action and has been shown to contain 22 Kedde-

positive substances.

Uzarigenin, calactin, calotropin, (differing stereochemistry at C-3 of the sugar moiety) coroglaucigenin, 4‟-O -β D-

glucopyranosylgofruside, 4‟ O-β-cellobiosylgofruside, calotropagenin and uzarin were isolated and characterized along with a new

genin and its 4 glycosides. β-Sitosterol, its glucoside and oleanolic acid were also isolated and identified [46, 48, 56]. Calotropagenin

was isolated from leaf of Asclepias curassavica [56]. The yield of calotropagenin obtained from Asclepias curassavica is greatly

increased by destruction of the naturally occurring glycosidase in the leaves by treating with boiling alcohol. Different cardenolides

like uzarigenin, coroglaucigenin and 4 additional new aglycons of the cardenolide series: asclepogenin (C23H32O6), clepogenin

(C23H32O6), cuarassavogenin (C23H32O7), ascurogenin (C23H32O7) were isolated from the extract of the leaves of Asclepias curassavica

[57]. The cardenolides in the latex and leaves of seven Asclepias species including Asclepias curassaica and Calotropis procera was

examined [48]. The latex of cardenolide-enriched species had greater proportions of lower polarity cardenolides, particularly those

with a spiro NS ring or keto at 3‟ of the sugar (uscharidin, uscharin, voroscharin. labriformin, labriformidin), than was present in the

leaves. Uscharidin, uscharin and voruscharin were isolated from the latex part of A. curassavica. Asclepin, calactin, calotoxin and

calotropin were separated from different parts of plant [29, 46-49, 54, 58-59].

Flavonol

Six flavonoid glycosides namely, quercetin 3-O-(2", 6"-α-L-dirhamnopyranosyl)-β-D-galactopyranoside, quercetin 3-O-β-D-

glucopyranozyl (1→6)-β-D-galactopyranoside, quercetin 3-O-(2"-O-α-L-rhamnopyranosyl) β-D-galactopyranoside, quercetin 3-O-α-

L-rhamnopyranosyl (1→6) - beta-D- glucopyranoside, quercetin 3-O-beta-D-galactopyranoside, quercetin 3-O-β-D-glucopyranoside

and an unidentified flavonoid mixture were isolated and characterized from the leaf part of plant [60]. Hyperoside and Isoquercetrin

were isolated from leaf part of A. curassavica [60].

www.iajpr.com

Page1

748


Phenol

Comparative studies on phenolic contents of some laticiferous plants were discussed [61]. Among the stems, leaves, flowers, and

latexes of 7 laticiferous plants, flowers of Asclepias curassavica had the highest total phenolic content (6.5 mg/g).

Aliphatic, alicyclic compounds and alkaloids

Phytochemical screening and study of lipids, flavonoids, carbohydrates and mucilage of Asclepias curassavica were done

[28]. The phytochemical investigation of Asclepias curassavica revealed the presence of β-sitosterol, β-amyrin, myristic, palmitic,

stearic, oleic, linoleic, linolenic, arachidic, and arachidonic acids, rutin and quercetin, glucose and fructose, and acidic mucilage [28].

Conduritol- F glucosides and terpenoidglucosides from several Asclepiadaceous plants including Asclepias curassavica were isolated

[62]. Alkaloids such as 2-methoxy 3-isopropyl pyrazine, 2-methoxy 3-isobutyl pyrazine, 2-methoxy 3-secondary butyl pyrazine were

isolated from the entire plant [63]. Active constituent‟s names and structures are given in Table 6.

Table 6: Active constituent of Asclepias curassavica

Active constituent Structure Parts of Plant References

Alicyclic

Conduritol F OH

OH

OH

OH

leaf

[62]

Conduritol F 3-O-beta-D-

glucoside

OH

OH

OH

O beta-D-glucoside

leaf [62]

Alkaloid

2-Methoxy-3-iso-butyl,

pyrazine

N

N

OMe

entire plant

[63]

2-Methoxy-3-iso-propyl,

pyrazine

N

N

OMe 2-Methoxy-3-sec-butyl,

pyrazine

N

N

OMe

Cardenolide

3'-Epi, 19-nor afroside

O O

O

O

CH3

OH

OH

H H

CH3

OH

H

OH

O

stem

[46]

www.iajpr.com

Page1

749


Asclepioside-1

Asclepioside-2,

Asclepioside-3,

Asclepioside- 4

O

OH

beta D-allomethyloside-O

CH3

O

aerial [47]

Asclepin

O O

O

O

H3C

O C

O

CH3

OH

H

CHO

H

CH3

OH

O

entire plant [29, 55, 58]

stem [46]

Asclepiogenin entire plant [57]

Ascurogenin leaf [57]

Calactin O

OH

O

CH

O

O

O

H

O

OH

H

H

CH3

HOH

stem

[46]

entire plant [59]

latex [49]

leaf

Calotoxin O

OH

O

CH

O

O

O

H

O

OH

HCH

3

OHH

OH

H

stem [46]

latex [49]

leaf

Calotropagenin O

OH

HO

CH

O

O

HO

H

leaf

[49]

[56]

16-alpha- Hydroxy,

calotropagenin

O

CH3

HHO

OH

O

CHO

OH

HO

seed [45]

Calotropin

OH

O

OH

O

CH

O

O

O

H

O

OH

H

H

CH3

stem

[46, 48, 50]

entire plant [59]

latex [49]

leaf

16-alpha-Hydroxy,

calotropin O

CH3

H

OH

O

CHO

OH

O

OOCH

3

OH

OH

seed [45]

www.iajpr.com

Page1

750


3'-O-beta-D-

Glucopyranosyl,

calotropin

O

CH3

H

OH

O

CHO

O

OOCH

3

O-beta D-glucose

OH

seed [45]

3'-O-beta-D-

Glucopyranoside, 16-

alpha- hydroxy, calotropin

O

CH3

H

OH

O

CHO

OH

O

OOCH

3

O-beta D-glucose

OH

seed [45]

Clepogenin

leaf [57]

12-beta-Hydroxy,

coroglaucigenin

O

CH3

H

HO

OH

O

OH

HO-H2C

seed [45]

stem [46]

4‟-O -β D-

Glucopyranosylgofruside

O

CH3

Hbeta D-allomethyl,

4 beta D-glucose-O

OH

O

CH2OH

OH

leaf [57]

4‟ O-β-

Cellobiosylgofruside

O

CH3

Hbeta D-allomethyl,

4 beta D-glu.-

4 beta D-glu-O

OH

O

CH2OH

OH

leaf [57]

Curassavicin

N

H2C O C

O

CH3

OH

CH3

HO

Entire plant [30]

Curassavogenin

leaf [57]

www.iajpr.com

Page1

751


Frugoside O

CH3

HO

OH

O

CH2OH

O

OHOH

OH

CH3

seed [45]

12-beta-Hydroxy,

frugoside

O

CH3

HO

OH

O

CH2OH

O

OHOH

OH

CH3

OH

seed [45]

12-beta-Hydroxy, 4'-O-

beta-D-glucopyranosyl

frugoside,

O

CH3

H

beta -D allomethyl-4- beta-D-glucose - O-

OH

O

HO-H2C

OH

seed [45]

4'-O-beta-Cellobiosyl,

frugoside

O

CH3

OH-H2C

H

beta -D allomethyl-4- beta-D-glu-

4-beta-D-glu - O-

OH

O

seed [45]

12-beta-Hydroxy, 4'-O-

beta-D- cellobiosyl,

frugoside

O

CH3

OH-H2C

H

beta -D allomethyl-4- beta-D-glu-

4-beta-D-glu - O-

OH

O

OH

seed [45]

Uscharidin O

OH

O

CH

O

O

O

H

O

OH

H

O

CH3

H

leaf

[49, 51]

latex [49]

stem [48, 50, 52]

Uscharin

NS

O

OH

O

CH

O

O

O

H

O

OH

HCH

3

H

stem [48, 52]

latex [49]

leaf

Uzarigenin O

OH

OH

CH3

O

stem [46]

www.iajpr.com

Page1

752


leaf [57]

Voruscharin

NHS

O

OH

O

CH

O

O

O

H

O

OH

HCH

3

H

latex [49]

stem [48, 52]

Flavonol

Hyperoside OH

O

OH

OH

O

O-beta D-galactoside

OH

leaf [60]

3-O-(2''-6''-alpha-

Dirhamnopyranosyl)- beta-

D-glucopyranoside,

Quercetin

O

O

OH

OH

CH3

HOH

O

O

C

H2

H

O

OH

OH

CH3

OH

OH

OH

H

O

OH

OH

O

O

OH

OH

leaf [60]

3-O-(2''-6''-alpha-L-

Dirhamnopyranosyl)-beta-

D-

galactopyranosidequerceti

n.

O

OH

OH

O

O

OH

OH

O

O

OH

OH

CH3

HOH

O

OC

H2

H

O

OH OH

CH3 OH

OH

OHH

leaf [60]

3-O-(2''-O-alpha-L-

Rhamnopyranosyl)- beta-

D- Galactopyranoside,

quercetin

O

OH

OH

O

O

OH

OH

OO

H

CH2

OH

O

H OH

OH

OHCH3OHOH

leaf

[60]

3-O-alpha-L-

Rhamnopyranosyl-(1-6)-

beta-D- glucopyranoside,

quercetin

O

OH

OH

O

O

OH

OH

O

CH3

OH

OH

OH

HO

OH

OHCH

2OH

H

leaf

[60]

www.iajpr.com

Page1

753


3-O-beta-D-

Glucopyranosyl, (1-6)-

beta-D- galactopyranoside

quercetin. O

OH

OH

O

O

OH

OHO

O

O CH

2

OHOH

OH

H

H

O

OHOH

CH

2

OH

leaf

[60]

Isoquercetrin

O

O

O

OH

OH

OH

HO

O

OH

H

H

OH

CH2OH

OH

leaf

[60]

Alkaloids entire plant [15]

Cardenolides/bufadienolid

es present latex [54]

leaf

[53]

seed [53]

Triterpenes latex [54]

CONCLUSION

The extensive literature survey exposed that Asclepias curassavica is important medicinal plant with diverse ethnomedical

and pharmacological spectrum. Various biological studies have been dedicated to this species, but a small number of them are useful

in evaluating its traditional uses. The plant shows the occurrence of many natural constituents which are responsible for wide-ranging

pharmacological and medicinal properties. In future research work, the evaluation needs to be carried out on Asclepias curassavica in

order to uses and preparation of the plant in their practical clinical applications, which can be recycled for the welfare of the mankind.

ACKNOWLEDGEMENTS

The authors are thankful to UGC (New Delhi, India) for providing financial assistance to GITAM institute of pharmacy,

GITAM University, Visakhapatnam, Andhra Pradesh, India.

REFERENCE

1. Hemavani C, and Thippeswamy B. Evaluation of antimicrobial activity of root extract of Asclepias curassavica. Recent Research

in Science and Technology 2012; 4(1): 40-43.

2. Stone BC. The flora of Guam. Micronesica 1970; 6:487

3. Wagner WL, Herbst DR and Sohmer SH. Manual of the flowering plants of Hawai'i. Revised edition. University of Hawai'i

Press, Honolulu 1999; 240.

4. Smith AC. Flora Vitiensis nova: A new flora of Fiji. Lawai, Kauai, Hawaii. National Tropical Botanical Garden 1988; 4:109-

110.

5. Whistler WA. Checklist of the weed flora of western Polynesia. Technical Paper No. 194, South Pacific Commission, Noumea,

New Caledonia 1988; p. 7.

6. Henty EE, and Pritchard GH. Weed of New Guinea and their control. 2nd edition. Division of Botany, Department of Forests,

Lae, Papua New Guinea 1975; 59.

7. Yuncker TG. Plants of Tonga. B. P. Bishop Museum Bull. 1959; 220:222-223.

8. Gupta ML, Gupta TK, Bhargava KPA. Study of antifertility effects of some indigenous drugs. Journal of Research in Indian

Medicine 1971; 6: 112-116.

9. John D. One hundred useful raw drugs of the kani tribes of Trivandrum forest division, Kerala, India. International Journal of

Crude Drug and Research 1984; 22(1): 17-39.

10. Duke JA. Amazonian ethnobotanical dictionary, Boca Raton, FL: “CRC Press” 1994; 181.

11. Oakes AJ, Morris MP. The West Indian Weed woman of the united states virgin islands. Bulletin of the History of Medicine

1958; 32: 164.

12. Mitra R, Mehrotra S, Mehrotra BN, Kapoor LD. Pharmacognostic study of Asclepias curassavica Linn. Bulletin Botanical

Survey of India 1974; 16 (1-4): 82-88.

13. Neto CC, Owens CW, Langfield RD, Comeau AB, Onge JS, Vaisberg AJ, Hammond GB. Antibacterial activity of some

Peruvian medicinal plants from the callejon de huaylas. Journal of Ethnopharmacology 2002; 79(1): 133–138.

www.iajpr.com

Page1

754


14. Ramirez VR, Mostacero LJ, Garcia AE, Mejia CF, Pelaez PF, Medina CD, Miranda CH. Vegetales empleados en medicina

tradicional norperuana. Banco Agrario Del Peru & Nacl Univ Trujillo, Trujillo, Peru 1988; 54.

15. Coee FG, Anderson GJ. Ethnobotany of the Garifuna of Eastern Nicaragua. Economic Botany 1996; 50(1): 71-107.

16. Barrett B. Medicinal plants of Nicaragua's atlantic coast. Economic Botany 1994; 48(1): 8-20.

17. Heinrich M, Kuhnt M, Wright CW, Rimpler H, Phillipson JD, Schandelmaier A, Warhurst DC. Parasitological and

microbiological evaluation of mixe Indian medicinal plants (Mexico). Jouranl of Ethnopharmacology 1992; 36(1): 81-85.

18. Zamora-Martinez MC. Pola CNP. Medicinal plants used in some rural populations of oaxaca, puebla and veracruz, mexico.

Jouranl of Ethnopharmacology 1992; 35(3): 229-257.

19. Flores JS, Ricalde RV. The secretions and exudates of plants used in Mayan traditional medicine. Journal of Herbs, Spices &

Medicinal Plants 1996; 4(1): 53-59.

20. Martinez MA. Medicinal plants used in a totonac community of the sierra norte de Puebla: Tuzamapan De Galeana, Puebla,

Mexico. Journal of Ethnopharmacology 1984; 11(2): 203-221.

21. Hirschhorn HH. Botanical remedies of south and central America, and the caribbean: an archival analysis. Part i. Journal of

Ethnopharmacology 1981; 4(2):129-158.

22. Zargari A. Medicinal Plants. Volume - 3, 5th edition, Tehran University Publications, Tehran, Iran 1992; 889.

23. Hirschmann GS, Rojas DE, Arias A. A survey of medicinal plants of minas gerais, brazil. Journal of Ethnopharmacology 1990;

29(2):159–172.

24. Schmeda-Hirschmann G, Rojas De Arias AA. Screening method for natural products on triatomine bugs. Phytotheraphy

Research 1992; 6(2): 68-73.

25. Caceres A, Menendez H, Mendez E, Cohobon E, Samayao BE, Jauregui E, Peralta E, Carrillo G. Antiogonorrhoeal activity of

plants used in Guatemala for the treatment of sexually transmitted diseases. Journal of Ethnopharmacology 1995; 48(2): 85-88.

26. Manandhar NP. An ethnobotanical survey of herbal drugs of Kaski district, Nepal. Fitoterapia 1994; 65(1): 7-13.

27. Manandhar NP. Medicinal folk-lore about the plants used as anthelmintic agents in Nepal. Fitoterapia 1995; 66(2): 149-155.

28. Karawya MS, Abdel Wahab SM, Hifnawy MS, El Gohary HM. Phytochemical screening and study of lipids, flavonoids,

carbohydrates and mucilage of Asclepias curassavica L. Egyptian Journal of Pharmaceutical Sciences 1982; 21(3-4): 309-16.

29. Patnaik GK, Dhawan BN. Pharmacological investigations on asclepin-a new cardenolide from Asclepius curassavica. Part I:

Cardiotonic activity and acute toxicity. Arzneim-Forsch1978; 28: 1095.

30. Lo KL, Chou YS, Huang H, Wang CK, Yang TH. The cardiotonic effect of curassavicin isolated from Asclepias curassavica.

Yao Hsueh Hsueh Pao 1964; 11: 80-84.

31. Feng PC, Haynes LJ, Magnus KE, Plimmer JR. Further pharmacological screening of some West Indian medicinal plants.

Journal of Pharmacy and Pharmacology 1964; 16: 115.

32. Barnes CS, Price JR, Hughes RL. An examination of some reputed antifertility plants. Lloydia 1975; 38(2): 135.

33. Vandenberghe DA, Ieven M, Mertens F, Vlietinck AJ, Lammens, E. Screening of higher plants for biological activities. II.

Antiviral activity. Journal of Natural Products 1978; 41(4): 463-467.

34. Mackeen MM, Khan MN, Samadi Z, Lajis NH. Brine shrimp toxicity of fractionated extracts of Malaysian medicinal plants.

Natural Product Science 2000; 6(3): 131-134.

35. Moulin-Traffort J, Giordani R, Regli P. Antifungal action of latex saps from Lactuca sativa L. and Asclepias curassavica L.

Mycoses 1990; 33(7-8): 383-392.

36. Chiappeta ADA, Francisco de Mello J, Maciel GM. Higher plants with biological activity - plants of Pernambuco. I. Revista do

Instituto de Antibioticos, Universidade Federal de Pernambuco 1983; 21(1-2): 43-50.

37. Kupchan SM, Knox JR, Kelsey JE, Saenzrenauld JA. Calotropin. a cytotoxic principle isolated from Asclepias curassavica. Life

Science 1964; 25(146): 1685–1686.

38. Li JZ, Qing C, Chen XC, Xiao-Jiang Hao, Hai-Yang Liu. Cytotoxicity of cardenolides and cardenolide glycosides from

Asclepias curassavica. Bioorganic & Medicinal Chemistry Letters 2009; 19: 1956–1959.

39. Bork PM, Schmitz ML, Kuhnt M, Escher C, Heinrich M. Squiterpene lactone containig Mexican Indian medicinal plants and

pure sesquiterpene lactones as potent inhibitors of transcription factor. FEBS Letters 1997; 402(1): 85-90.

40. Verpoorte R, Dihal PP, Medicinal plants of Surinam IV. Antimicrobial activity of some medicinal plants. Journal of

Ethnopharmacology 1987; 21(3): 315-318.

41. George M, Pandalai KM. Investigations on plant antibiotics. Part iv. Further search for antibiotic substances in Indian medicinal

plants. Indian J Med Res 1949; 37(2): 169-181.

42. Shivaprasad HV, Rajesh R, Nanda BL, Dharmappa KK, Vishwanath BS. Thrombin like activity of Asclepias curassavica L.

latex: Action of cysteine proteases. Journal of Ethnopharmacology 2009; 123: 106–109.

43. Chakraborty S, Siegenthaler J, Buchi ER. Corneal edema due to Asclepias curassavica. Archives of Ophthalmology 1995;

113(8), 974-975.

44. Hassan JR, We Reed HL. 1952. Studies on species of Asclepias. Toxicology, pathology, and pharmacology. Journal of

Americian Pharmaceutical Association 1952; 41: 298-300.

45. Abe F, Mori Y, Yamauchi T. Cardenolide glycosides from the seeds of Asclepias curassavica. Chemical and Pharmaceutical

Bulletin 1992; 40(11): 2917-2920.

46. Abe F, Mori Y, Yamauchi T. 3‟-epi-19-norafroside and 12-Hydroxy coroglucigenin from Asclepias curassavica. Chemical and

Pharmaceutical Bulletin 1991; 39(10): 2709–2711.

www.iajpr.com

Page1

755


47. Cherdmancascon S, Mors WB. On cardiac glucosides of Asclepias curassavica, toxic plant of Brazilian pastures. Arquivos do

Jardim Botanico do Rio de Janeiro 1958; 16: 101.

48. Groeneveld HW, Binnekamp A, Seykens D. Cardenolide biosynthesis from acetate in Asclepias curassavica. Phytochemistry

1991; 30(8): 2577-2585.

49. James NS, Carolyn JN, and Mark LS. Cardenolides in the latex and leaves of seven Asclepias species and Calotropis procera.

Phytochemistry1982; 21(9): 2343-2348.

50. Lee SM, Seiber JN. Biosynthetic preparation of cardenolides from [1-14c] acetic acid by stem discs of the milkweed Asclepias

curassavica. Phytochemistry 1983; 22(4): 923-927.

51. Groeneveld HW, Van berkel YEM, Binnekamp A, Seykens D. Some quantitative aspects of cardenolide synthesis from malonate

in Asclepias curassavica. Phytochemistry 1994; 37(6): 1605-1610.

52. Groeneveld HW, Van Den Berg B, Elings JC, Seykens D. Cardenolide biosynthesis from malonate in Asclepias curassavica.

Phytochemistry 1990; 29(11): 3479-3486.

53. Duffey SS, Scudder GGE. Cardiac glycosides in North American Asclepiadaceae, a basis for unpalatability in brightly coloured

hemiptera and coleoptera. Journal of Insect Physiology 1972; 18: 63.

54. Groeneveld HW, Van Der Made LA. Cardenolide and triterpene synthesis in the laticifers of Asclepias curassavica. Acta

Botanica Neerlandica 1982; 31(1): 5-10.

55. Singh B, and Rastogi RP. Structure of asclepin and some observations on the NMR spectra of Calotropis glycosides.

Phytochemistry 1972; 11: 757-762.

56. Tschesche R, Snatzke G, Grimmer G. Calotropagenin from Asclepias curassavica. Naturwissenschaften 1959; 46(8): 263-264.

57. Tschesche R, Forstmann D, Rao Varanasi Hrishna M, Plant cardiac poisons. XXXIV. Cardenolide components of Asclepias

curassavica. Chemische Berichte 1958; 91: 1204-11.

58. Dhawan BN, Patnaik GK. Investigation on some new cardioactive glycosides. Indian Drugs 1985; 22(6): 285-290

59. Enson JM, Seiber JN. High-speed liquid chromatography of cardiac glycosides in milkweed plants and monarch butterflies.

Journal of Chromatography 1978; 148: 521.

60. Haribal M, Renwick JAA. Identification and distribution of oviposition stimulants for monarch butterflies in host‟s and non

hosts. Journal of Chemical Ecology 1998; 24: 891–904.

61. Marimuthu, S., Kothari, I.L., 1986. Comparative studies on phenolic contents of some laticiferous plants. Indian Botanical

Contactor 3(1), 11-14.

62. Abe F, Yamauchi T, Honda K, Hayashi N. Conduritol F glucosides and terpenoid glucosides from Cynanchum liukiuense and

distribution of conduritol F glucosides in several Asclepiadaceous plants. Chemical and Pharmaceutical Bulletin 2000; 48(7):

1090-1092.

63. Rothschild M, Moore BP, Brown WV. Pyrazines as warning odour components in the monarch butterfly, Danaus plexippus, and

in moths of the genera Zygaena and Amata (Lepidoptera). Biological Journal of the Linnean Society of London 1984; 23(4):

375-380.

54878478451014390

Submit your next manuscript to IAJPR and take advantage of:

• Access Online first

• Double blind peer review policy

• No space constraints

• Rapid publication

• International recognition

Submit your manuscript at: [email protected]

mailto:[email protected]

indo american journal of pharmaceutical research, … · indo american journal of pharmaceutical...

Documents