.

115 TJPS 2016, 40 (3): 115-131

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Calotropis procera

: A phytochemical

and pharmacological review

Gaurav Parihar, Neelam Balekar*

IPS Academy, College of Pharmacy, Hukhmakedhi, Indore, Madhya Pradesh, India

ABSTRACT

Medicinal plants are used from the ancient time as the major sources of drugs. The fact is

that we can obtain many of the presently available drugs, either directly in the extract form

or in the modified synthetic form. Naturally, plants have the ability to synthesize products

beneficial for us namely as phytoconstituents that are used to perform biological functions,

which also protect us against predators such as virus fungi and other microorganisms. The

phytoconstituents obtained from the natural products are one of the most successful strategies

for the discovery of new drugs. Calotropis procera is a plant which is used in several traditional

medicine and folklore systems to cure various ailments as reported in the Hindu literature.

It is widely used in the Indian traditional medicinal system as well as in Arabic, Unani, and

Sudanese systems. C. procera is also used by various tribes of the world as a curative agent

for ailments such as skin disease and elephantiasis. Different parts of the plant have been

reported to possess various phytochemicals containing cardiotonic agents such as calotropin,

calotropagenin, calotoxin, calotropagenin and voruscharine, steroids, di and triterpenes such

as stigmasterol, β-sitosterol, flavonoids, polyphenolic compounds, and various newer reported

hydrocarbons and proteins. This shrub is known to possess a wide range of pharmacological

activities such as anticancer, acaricidal, schizonticidal, antimicrobial, anthelmintic, insecticidal,

anti-inflammatory, antidiarrheal, anticancerous, and larvicidal activities with other beneficial

properties. C. procera is small, erect shrub, which is used in several herbal and empirical

medicines to cure simple and deadly diseases and disorders. It is also reported widely in

various folklore preparations and ethnomedicines. This review is a profound attempt to stack

the information concerning pharmacognostical, phytochemical, and pharmacological features

of C. procera shrubs.

INTRODUCTION

alotropis procera (Arka) is an important drug in the

monograph of Ayurveda, and it is known in India

from the earliest time (Figure 1). It was mentioned by

Hindu writers and the ancient sacrificial rites many years ago.

There are two common species of Calotropis reported in the

literature, viz., C. procera (Ait.) R.Br. and Calotropis gigantea

(Linn.) R.Br. mentioned by the ancient writers. Both the species

consists of similar types of phytoconstituents discovered till

now and may be used as substitutes for one another might

have similar effects. Three varieties of Arka are mentioned

in the Hindu literature of Dhanvantari Nigantu as Suklarkah,

Rajarkah, and Sveta mandarah. It is widely used in the Indian

traditional medicinal system as well as in the other available

treatments such as Arabic, Unani, and Sudanese and for the

various diseases. C. procera is also used by various tribes of

the world as a curative agent for ailments such as skin disease,

elephantiasis, toothache, asthma, leprosy, and rheumatism [1].

Different parts such as leaves, roots and bark, flower, fruits, stem,

and latex of the plant have been reported to possess various

phytochemicals which might possess various pharmacological

activities. The coarse shrub possesses acaricidal, schizonticidal,

antimicrobial, anthelmintic, insecticidal, anti-inflammatory,

antidiarrheal, anticancerous, and larvicidal activities with

other beneficial properties [2]. The plant is described as a

golden gift for humankind containing cardiotonic agents such

as calotropin, calotropagenin, calotoxin, calactin, uscharin,

amyrin, amyrin esters, uscharidin, coroglaucigenin, frugoside,

corotoxigenin, calotropagenin, and voruscharine used in the

therapeutic treatment [2].

Different compounds such as norditerpenic esters, organic

carbonates, the cysteine protease procerain, alkaloids, flavonoids,

sterols, and numerous cardenolides made this plant of scientific

attraction for centuries. Hence, in this review, an account of

reported pharmacological actions of the plant with reported

active chemical constituents were discussed in this study.

Review Article

Corresponding Author:

Dr. Neelam Balekar,

IPS Academy, College of

Pharmacy, Hukhmakedhi,

Rajendra Nagar, A.B.

Road, Indore - 452 012,

Madhya Pradesh, India.

Phone: +91-9893405071,

Fax: +91-7314041627.

E-mail: neelambalekar@

gmail.com

Received: Apr 8, 2016

Accepted: Aug 29, 2016

Published: Sep 26, 2016

Keywords:

Arka, phytoconstituents,

plant pharmacology,

traditional medicine

Parihar and Balekar: C. Procera: A review

116 TJPS 2016, 40 (3): 115-131

http://www.tjps.pharm.chula.ac.th

DESCRIPTION

Habitat

C. procera favors open habitat with little competition. The plant

of this species grows in dry habitat where rainfall is limited

to 150 to 1000 mm and also found in the area of excessive

drained soil as much as 2000 mm of annual precipitation. It

is also found in the common habitat of road-side, beachfront

dunes, and widely disturbed in the urban areas. C. procera is

also found at the elevated areas up to 1,000 m. Because the

plant is easy to propagate and manages and can grow under

the xerophytic condition, sometimes it is also grown as an

ornamental plant in dry or coastal areas [2,3].

Geographical Distribution

C. procera is inborn to Southern Asia and Indo-China to

Malaysia, Macaronesia, West Africa North and East Africa,

Madagascar, and Arabian Peninsula. The plant is naturalized

in Australia, Central America, North, South America, and

West Indies. The species is now accepted and culture in many

countries such as Mexico, Central and South America, Pacific

islands, Australia, and the Caribbean [2,4].

Scientific Classification

Taxonomy Calotropis procera (Ait.) Ait.f. Kingdom:

Plantae – Plants; Subkingdom: Tracheobionta – Vascular

plants; Superdivision: Spermatophyta – Seed plants;

Division: Magnoliophyta – Flowering plants; Class:

Magnoliopsida – Dicotyledons; Subclass: Asteridae; Order:

Gentianales; Family: Asclepiadaceae; Genus: Calotropis

R.Br. – Calotropis; Species: C. procera (Ait.) Ait.f. [1].

Synonyms/Other Latin Names

Asclepias procera Aiton, common vernacular names (Sanskrit)

Arka, (Hindi) Aaka. Giant Indian Milkweed. Sodom Apple,

Small Crown Flower, Rooster tree, French Cotton in English.

Remiga (Malaysia), Dok Hak (Laos), Kapal-kapal (Philippines),

Nam t[it] b[at] (Vietnam), Pomme de Sodome (French), Rubik

(Indonesia), Mudarpflanzer (German), Algodon Extranjero

(Spanish), Ipekag (Turkish), Oshar (Arabic), Calotropo

(Italian), Po Thuean, Paan Thuean (northern), and Rak

(central) in Thailand [1,2,5].

Botanical Description

The plant is an evergreen, soft-wooded, perennial shrub; small

tree attains a maximum height up to 2.5 m (maximum 6 m).

A copious amount of white sap generates whenever any part

of the plant is cut. The bark is corky, furrowed, and light gray.

The root is simple, branched, and woody at base and covered

with a fissured, corky bark, branches has very deep stout

root with few branches. The leaves are opposite-decussate,

simple, subsessile, and exstipulate; the leaves are slightly

leathery and having a fine coat of soft hairs that sometimes

sting too. Flowers are shallow bell-shaped, like a campanula,

bracteate, complete, bisexual, actinomorphic, pentamerous,

hypogynous, pedicellate, multiflowered, umbellate, peduncled

cymes with axillary or terminal inflorescence. Five sepals, 5

lobed shortly united that are 4-5 mm long. Five-lobed petals

(Corolla), gamopetalous, twisted aestivation. Androecium

has five stamens, gynandrous, anther dithecous, coherent.

Gynoecium is bicarpellary, apocarpus, and styles are united at

their apex, peltate stigma with five lateral stigmatic surfaces.

Anthers are adnate to the stigma forming a gynostegium. Fruit

is simple, fleshy, inflated, and subglobose to obliquely ovoid

follicle. Seeds are present in large amount, small, flat, obovate,

compressed with silky white pappusat the one end, 3 cm or

more long [1,2,5,6].

Ethnomedical (Traditional) Uses

The leaves were reported to use in sun worship from the Vedic

times. Secretions from the root bark were used by Hindu

physicians to treat skin diseases, cough, intestinal worms,

ascites, and anasarca and also in enlargements of abdominal

viscera, etc. The milky juice was considered as a drastic

purgative and caustic. Flowers were considered to improve

digestion, catarrh, and increase appetite. The root bark was

also used to treat elephantiasis. Calotropis latex is used and

applied intact in the preparations for toothache. The flowering

tops were also used to treat asthma. The plant was also used

in the treatment of leprosy, hepatic, and splenic enlargements.

The leaves were boiled, and oily preparations were made

and used in the treatment of paralysis. Leaf powder was

considered as a substitute for ipecacuanha and also possesses

the properties of Gutta-persica also used in wound healing.

The juice was used for the purpose of infanticide and was

sometimes given to women to induce abortion. Tanners used

the milky juice to remove hair from hides [2,7].

Pear-shaped fruit and latex have medicinal properties.

The raw latex is often considered poisonous, but reports of

its toxicity may be exaggerated. A safe, effective dose could

be obtained by scooping out the seeds and pulp from a halved

ripe fruit and drinking sheep, goat, or camel milk from the

remaining green skin “cup.” Poultices made from the leaves

used to heal rheumatism. Levey identifies the Sodom apple

with Ladanum asclepiad, which Al-Kindi used in a dentifrice,

for lengthening the hair, and in a formula for exterminating

worms and purifying the air during an epidemic [8].

The powder of the root mixed with milk of goat is used

in epilepsy; route of application is in the nostrils. The tribes

of the Varanasi use latex to remove worms from teeth and in

the preparations of toothache. Traditionally, C. procera bark is

used to treat cholera, extracting Guinea worms, and digestion.

The drug is well known to enhance bile secretion and has a

sedative effect on intestinal muscles. The tender leaves are

also used to cure migraine. An ethnomedicinal profile of

different plant parts of C. procera was compiled by Verma

et al., 2010 [9].

PHYTOCHEMICAL REPORTS

A vast number of research and review articles are published

on the phytochemical and screening properties of C. procera.

All parts of the plant have toxic potential, due to the presence

of cardenolides (cardiac glycosides). The latex was found

to be richest in cardenolides, which is already mentioned in

the literature. According to research, the leaf of the plant

consists of cardenolides 162 mg/g at dry weight and 2 mg/g

Parihar and Balekar: C. Procera: A review

117 TJPS 2016, 40 (3): 115-131

http://www.tjps.pharm.chula.ac.th

total dry weight. The important cardenolides found in the

plant are voruscharin, uscharidin, uzarigenin, calotroposide,

calactin, calotoxin, uscharin, ascleposide, calotropagenin,

coroglaucigenin, calotropin, proceroside, proceragenin,

and syriogenin. Many of these compounds formed in the

mechanism of extraction when hydrolyzed in a chemical

reaction. Latex differs in the quantities of cardenolides from

the other plant parts stem, fruit, leaves, and root bark. The

main cardenolides in the various parts of the plant are uscharin

and calotropagenin in the latex; calotropin and calotropagenin

in the leaves; uscharidin, calotropin, proceroside, and

calactin in the stem; calotoxin and calactin in the root bark;

coroglaucigenin and uzarigenin in the fruit pericarp. The seeds

contain 0.23-0.47% cardenolides, mainly coroglaucigenin or

frugoside [10].

Besides the cardenolides, other phytochemicals are also

reported from the plant such as sterols, flavonoids, coumarins,

alkaloids, triterpenes, saponins, tannins, and hydrocarbons

were isolated from the plant. The major flavonoid is rutin

(quercetin-3-rutinoside): Roots contain 1.7%, stem 4.8%,

leaves 5.0%, flowers 7.6%, and latex 9.7%. The plant is also

reported to contain resins, fatty acids, proteases, hydrocarbons,

amino acids, and many minerals. The polyphenol content

in different plant parts varies from 3.3% (leaf) to 4.9%

(stem) [11].

The flowers mainly contain α-and β-amyrins, an alkaline

phosphate, cyaindin-3-rhamnoglucoside, cycloart-23-en-3β,

25-diol, cyclosadol, multiflorenol, procestrol, quercetin-3-

rutinoside, β-sitosterol, β-sitost-4en-3one, and stigmasterol.

Cyanidin-3-rhamnoglucose and the triterpene calotropenyl

acetate are found in the flowers [12].

The leaves contain ascorbic acid, calactin, calotoxin,

calatropagenin, calotropin, polysaccharide containing

D-arabinose, D-glucose, D-glucosamine and L-rhamnose,

calotropagenin, and 3-proteinase. The latex contains

calotropin, α-calotropeol, 3-epimoretenol, gigantin, giganteol,

isogiganteol, α-lactuceryl acetate, α-lactuceryl isovalerate,

lupeol, proceroside, proceragenin, syriogenin, taraxast-20α-

(30)-en-(4-methyl-3-pentenoate), 3’-thiazoline cardenolide

uscharidin, uzarigenin, voruscharin and β-sitosterol, powerful

bacteriolytic enzyme in latex [13]. The latex contains 11-23%

rubber, the triterpenoids α- and β-amyrin, lupeol, taraxasteryl

acetate, α-and β-calotropeol, 3-epimoretenol, multiflorenol,

cyclosadol, several triterpene esters, the sterols β-sitosterol

and stigmasterol, the non-toxic cysteine proteases calotropin,

procerain and procerain-B and the alkaloid choline [13].

The root-bark contains benzolisoleneolone,

benzollineolone, long-chain fatty acids, and C (18) isoursane.

The plant also reported to contain calactinic acid, choline and

O-pyrocatechuic acid, β-sitosterol, taraxasterol, its φ-isomer:

taraxasteryl isovalerate and taraxasteryl acetate [14]. The

Presence of four new ursane-type triterpenes: Vrsa-13(18),

19(29)-diene-3α-yl-acetate, 18αH-urs-19(29)-en-3-one,

18αH-ursa-12, 20(30)-diene-3 α -yi-acetate and 18αH-urs-12-

en-3α-ol, were reported from the root bark [15]. Mudarine

as principal cardioactive constituent present in the leaves

is reported by Chaudhari [16]. Carruthers isolated and

characterized isorahamnetin-3-O-rutinoside, isorahamnetin-

3-O-glucopyranoside and taraxasteryl acetate, flavonoids from

Calotropis [12]. A yellow resinous substance from root bark

was also found by Sharma [17]. From the root bark, several

digitanol glycosides were isolated, which lack cardiac activity.

Four new ursane-type triterpenes calotroprocerol

A, calotroproceryl acetate A, calotroprocerone A, and

calotroproceryl acetate B from the root bark of C. procera

were isolated and structure elucidated in addition to five

known compounds [18]. Two labdane-type di terpenic

galactosides have been isolated for the first time from the

roots of C. procera, and structures are established as Labdan-

18-ol-β-D-galactofuranoside and Labdan-3 β-ol-11, 15-olide-

18,20-dioic acid-3 β-D-galactofuranoside [19]. In a study,

phytoconstituent of leaves hexane extract of C. procera was

investigated qualitatively and quantitatively by GC-MS. 12

major phytocompounds were identified and estimated. The

highest peak area was obtained by Ergost-5-en-3-ol (C

O),

and the lowest peak area was obtained by 9 octadecenoic acid

9-Octadecenoic acid (Z)-(C

) [20].

The ethyl acetate fraction of the methanolic extract

of the root barks of C. procera (Asclepiadaceae) resulted in

the identification of a new cardenolide glycoside named

proceraside A [21]. Three new cardenolides, along with eight

known ones, were isolated from the latex of C. procera [22].

Two new cardenolides, named ischarin and ischaridin, were

isolated from C. procera Ait. (Asclepiadaceae) [23]. The

n-BuOH fraction of the root bark of C. procera (Ait) R.Br. Seven

new oxypregnane oligoglycosides: Calotroposides H-N (1-7)

were isolated and identified [24].

Beside this, various parts of the plant possess

various phytochemicals reported till date. Various newer

phytochemicals reported till now; Table 1 shows the chemical

structures of phytoconstituents present in C. procera.

PHARMACOLOGICAL ACTIVITIES

The literature of the plant revealed us that various parts of

the plant such as root bark, stem bark, leaf, flower, and latex

and their extracts, fraction, and isolated compound showed

significant anticoagulant, antidiarrheal, anti-inflammatory,

antioxidant, antiulcer, analgesic, cough-suppressing,

hepatoprotective, smooth muscle-contracting, neuromuscular

blocking, spermicidal, and wound healing activity. Various

pharmacological activities of the plant parts reported on

Calotropis procera are shown in Table 2.

Analgesic and Antinociceptive Activity

In this study, analgesic activity of dry latex (DL) of C. procera

has evaluated. The effect of DL at a dose of 415 mg/kg

against acetic acid-induced writhing was more pronounced

as compared to an oral dose of aspirin (100 mg/kg). DL

(830 mg/kg) produced marginal analgesia in tail-flick model

which was comparable to aspirin [25,26].

Antinociceptive effect of proteins from the C. procera latex

using three different experimental models of nociception - acetic

acid, formalin-induced abdominal constrictions, and hot plate

test in mice - was evaluated. The latex protein fraction at the

doses of 12.5, 25, and 50 mg/kg showed the antinociceptive

effect in a dose-dependent manner, which is independent of

the opioid system [27,28].

Parihar and Balekar: C. Procera: A review

118 TJPS 2016, 40 (3): 115-131

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(Contd...)

Compound names Plant

part

References

Steroid

Procesterol

(24S)-24-ethyl-stigmast-

4-en-6a-ol-3-one

Flower [10]

Ergost-5-en-3-ol Leaves [41]

ß-Amyrin Root

bark

[26]

α-Amyrin Root

bark

[26]

Calotropin

12β-O-benzoyl-3β,14β,17β-

trihydroxypregnane 20-one

Roots [42]

Table 1: Secondary metabolites of Calotropis procera (R.Br.)

Compound names Plant

part

References

Taraxasterol Root

bark

Leaves

[42]

α-amyrin acetate

Urs-12 -en-3 -olyl acetate

Roots [26]

ß-Amyrin acetate Root

bark

[26]

Proceraursenolide

18 a H - urs - 1 2 en - 3 , 25 - olide

Roots [43]

Calotroprocerone-A

ursa-5,12,20(30)-trien-18aH-3-one

Root

bark

[44]

Table 1: (Continued)

(Contd...)

Parihar and Balekar: C. Procera: A review

119 TJPS 2016, 40 (3): 115-131

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(Contd...)(Contd...)

Compound names Plant

part

References

DI and triterpenes

Calotropenyl acetate

Urs-19(29)-en-3-ol, acetate, (3beta)

Root

bark

[44]

Gofruside

Corotoxigenin 3-O-β-D-

allomethyloside)

Roots [42]

Lupeol Root

bark

[43]

3b,27-dihydroxy-urs-18-en-

13,28-olide

Latex [45]

urs-19(29)-en-3-yl acetate Latex [45]

Table 1: (Continued)

Compound names Plant

part

References

β-Sitosterol Latex [45]

Stigmasterol Latex [45]

Stigmasta-5,22-dien-3-ol Leaves [20]

Multiflorenol

urs-19(29)-en-3-b-ol

Latex [45]

3b,27-dihydroxy-urs-18

-en-13,28-olide

Latex [45]

Table 1: (Continued)

Parihar and Balekar: C. Procera: A review

120 TJPS 2016, 40 (3): 115-131

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(Contd...)

Table 1: (Continued)

Compound names Plant

part

References

Procerursenyl acetate

urs-18a-H-12, 20 (30)-diene-3ß-yl

acetate

Roots [26]

Benzoyllineolone Root bark [26]

Diterpene

3,7,11,15 tetramethyl hexadecanyl

6′-methyl hept-5′-enyl ether (phytyl

isooctyl ether)

Roots [46]

Benzoylisolineolone Root bark [26]

Diterpene

3,7,11,15 tetramethylhexadecanoyl

-β-D-glucopyranosyl

-(2→1)-β-D-glucopyranosyl-(2→1)-β-

D-glucopyranosyl(2→1)-β-D-

glucofuranoside

(dihydrophytoyl tetraglycoside)

Roots [46]

Compound names Plant

part

References

Procerasesterterpenoyl

triglucosideDiterpene

2,6,10,14,18-

pentamethylnonadecanoyl‑β-D

glucopyranosyl-(2→1)-

β-D-glucopyranosyl

-(2→1)-β-D-glucopyranoside

Roots [46]

Uscharidin Latex [26]

18 H-urs-12, 2 0(30)-dien-3-yl acetate Roots [43]

Calotroprocerol–A

ursa-5,12,20(30)-trien-18aH-3b-ol

Root

bark

[44]

Urosolic acid Leaves [25]

Table 1: (Continued)

(Contd...)

Parihar and Balekar: C. Procera: A review

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Compound names Plant

part

References

Calotroproceryl acetate A

ursa-5,12,20(30)-trien-18aH-3b-yl

acetate

Root

bark

[44]

Pseudo-taraxasterol acetate Root

bark

[44]

Calotropursenyl acetate-B Root

bark

[44]

Terpenoid glycosides

bisabolan-11,14-diol-14-b-D

-glucopyranosyl-(1→2)

-b-Dglucopyranoside

Roots [43]

2-limonenyloxybenzoyl-

1β-D-glucopyranosyl

-(1→2)-β-D-glucopyranosyl-(1→2)

-β-D-glucuronopyranosyl-(1→2)-β-D

-glucuronopyranoside

Roots [43]

Table 1: (Continued)

Compound names Plant

part

References

1,2-dihexadecanoyl -3-phosphatyl

glycerol

Roots [43]

Polyphenolic compounds

Gallic acid Whole

plant

[47]

(−) Epicatechin Whole

plant

[47]

Ferulic acid Whole

plant

[47]

p-coumaric acid Whole

plant

[47]

Vanillic acid Whole

plant

[47]

n-tetradecanyl n-hexadec-9-enoate

(n -tetradecanyl palmitoleate)

Roots [43]

Table 1: (Continued)

(Contd...) (Contd...)

Parihar and Balekar: C. Procera: A review

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(Contd...)

Compound names Plant

part

References

Hydrocarbons

(E)-Octadec-7-enoic acid Root

bark

[44]

4-hydroxy-4-methylpentan-2-one Latex [48]

2,3,4-trimethylhexane Latex [48]

Decane Latex [48]

n-Pentadecane Latex [48]

2,6 dimethyl tetra-1,5-decaene Latex [48]

n-Eicosane Latex [48]

3,7,11-Trimethyl-2,6,10,12

-pentadecatrien-1-ol

Latex [48]

2,6,10,15,19,23-Hexamethyl

-2,6,10,14,18,22-tetracosahexaene

Latex [48]

1,3,5-Triisopropylbenzene Latex [48]

Napthalene decahydro2,6 dimethyl Leaves [20]

2-H Benzofuranone 5,6,7, 7A

tetrahydro 4,4,7A trimethyl

Leaves [20]

6,10,14-trimethyl, Pentadecanone -2 Leaves [20]

Table 1: (Continued)

Compound names Plant

part

References

Hexadaconic acid, methyl esters Leaves [20]

9-Octadecenoic Acid (Z)- Leaves [20]

9,12,15-Octadecatrienoic acid, methyl

ester, (Z, Z, Z)-2-Hexadecen-1-ol,

3,7,11,15-tetramethyl-,

[R-[R*, R*-(E)]]-

Leaves [20]

(6Z), (9 Z) Pentadecadien 1-ol Leaves [20]

Farnesol isomer Leaves [20]

Tetratetracontane Leaves [20]

Proceranol

n-triacontan -10ß-ol

Roots [29]

N-dotriacont-6-ene Roots [29]

Glyceryl mono-oleolyl-2-phosphate Roots [29]

Table 1: (Continued)

(Contd...)

Parihar and Balekar: C. Procera: A review

123 TJPS 2016, 40 (3): 115-131

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(Contd...)

Compound names Plant

part

References

Methyl myrisate, Roots [29]

Methyl behenate Roots [29]

(E)-3-(4-methoxyphenyl-2-O-beta

-D-4C1-glucopyranoside)-methyl

propenoate

Leaves [49]

Ž2‑propenyl‑2‑hydroxyethyl

carbonate

Latex [50]

Acetic acid Root

bark

[26]

Isovaleric acid Root

bark

[26]

Choline Latex [26]

Cardenolides

Cardenolide

2’’-oxovoruscharin

Root

barks

[41]

Table 1: (Continued)

(Contd...)

Table 1: (Continued)

Compound names Plant

part

References

Calotropagenin Leaves [25]

Calotropin Latex [25]

Calotoxin Latex [25]

Calactin Latex [25]

Voruscharin Latex [25]

Parihar and Balekar: C. Procera: A review

124 TJPS 2016, 40 (3): 115-131

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Compound names Plant

part

References

Proceroside Flower [25]

Proceragenin Flower [25]

Voruscharin a-calotropeol Flower [25]

Uzarigenin Latex [26]

Syriogenin Latex [26]

(Contd...)

Table 1: (Continued) Table 1: (Continued)

Compound names Plant

part

References

Uscharin Latex [26]

Flavonoids

Quercetin-3 rutinoside Latex [26]

Quercetin 3-O-rutinoside Stem,

leaves

and

flower

[51]

Quercetagetin-6-methyl ether

3-O-beta-D-4C1-galacturonopyranoside

Leaves [49]

(Contd...)

Parihar and Balekar: C. Procera: A review

125 TJPS 2016, 40 (3): 115-131

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Compound names Plant

part

References

Isorhamnetin-3-O-rutinoside Leaves [26]

Isorhamnetin-3-O-robinobioside Leaves [26]

Carbohydrates

D-arabinose Flower [26]

Glucose Flower [25]

Glucosamine Flower [25]

L-rhamnose Flower [25]

α-rhamnose Leaves [26]

Table 1: (Continued)

Anticonvulsant Effects

The anticonvulsant activity by maximal electroshock seizures

(MES), pentylenetetrazol (PTZ), lithium-pilocarpine, and

electrical kindling seizures of C. procera root aqueous and

chloroform extracts in rats was performed [29]. In the MES

test and the PTZ test, the chloroform extract showed a highly

significant effect. Both the extracts also inhibited convulsions

induced by lithium-pilocarpine and electrical kindling [26].

Antimalarial Activity

The ethanolic extracts of the different parts of C. procera

showed IC

values ranging from 0.11 to 0.47 mg/ml against

Plasmodium falciparum MRC20 CQ-sensitive strain and from

0.52 to 1.22 mg/ml against MRC 76 CQ-resistant strain,

flower, and bud extracts being the most effective. Although

220, 440 times less effective than CQ, these extracts deserve

further studies aimed at the identification of the active

constituents [25].

Anthelmintic Activity

The anthelmintic activity of C. procera flowers in comparison

with levamisole was evaluated through in vitro and in vivo

studies on live Haemonchus contortus. In the in vitro study

crude aqueous (CAE) and crude methanolic (CME) extracts,

and for in vivo study, CAE, CME extracts and crude powder

(CP), of flowers were used. Egg count percent reduction was

recorded as 88.4% and 77.8% in sheep treated with CAE and

CP at 3 g/kg

-1

; CME was found least effective in (20.9%)

reduction in ECR. All the extracts exhibited lower activity than

that exhibited by levamisole (97.8-100%). Cavalcante et al.

evaluated the chemical composition and in vitro activity of

latex on H. contortus [26,28,30].

Antioxidant and Antidiabetic Activity

The antioxidant activity of dried latex (DL) of C. procera and

antidiabetic effect against alloxan-induced diabetes rats was

evaluated. The oral dose of DL at 100 and 400 mg/kg was

administered. The result revealed us that there is decrease in

blood glucose and increase in the hepatic glycogen content. Tsala

et al. evaluated the antioxidant activity of the ethanol extract of

C. procera bark against surgical wounds [25,28,31,32].

Myocardial Infarction

C. procera latex was evaluated for protection against

isoproterenol (20 mg/100 g)-induced myocardial infarction

in albino rats. The pretreatment of ethanolic latex extract at

a dose of 300 mg/kg orally three times a day for 30 days,

significantly reduces elevated marker enzymes (serum

glutamic-pyruvic transaminase, serum glutamic oxaloacetic

transaminase, and alkaline phosphatase) level in serum and

heart homogenates [28].

Schizontocidal Activity

The effect of crude fractions of flower, bud, and root against

a chloroquine sensitive strain, MRC 20 and a chloroquine

resistant strain, MRC 76 of P. falciparum were evaluated.

The effectiveness of its fractions was compared with the

CQ-sensitive strain than the CQ-resistant strain in vitro [28].

Parihar and Balekar: C. Procera: A review

126 TJPS 2016, 40 (3): 115-131

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Anticancer and Cytotoxic Properties

The anticancer and cytotoxic properties of the DL of C. procera

in transgenic mouse model of hepatocellular carcinoma

were performed and found complete protection against

hepatocarcinogenesis. There was a significant lowering of

serum vascular endothelial growth factor level and extensive

cell death in both Huh-7 and COS-1 cells while AML12 cells

were found live. This was accompanied by extensive

fragmentation of DNA in Huh-7 and COS-1 cells. No change

in the levels of Bcl

and caspase 3 was observed; these are

the canonical markers of apoptosis. Gurung et al. found of

the anticancer bioactive compound proceraside by molecular

docking with macromolecules involved in the cell cycle and

DNA replication [28,31,33,34].

Antimicrobial Activity

The antimicrobial activity of the leaf extracts of C. procera

was evaluated, and the inhibitory effect of extract of latex of

C. procera against Candida albicans was observed [25,26]. The

antibacterial activity of a new cardenolide, 7B, 14B-dihydroxy-

5-card-20(22) enolide (proceragenin) of C. procera was

evaluated [26] which was found to be active against

Pseudomonas pseudomallei, a causative agent of melioidosis.

All the leaf extract fractions completely inhibited the growth of

the tested organisms. The antimicrobial activity of C. procera

was evaluated against some of the tested microorganisms

(Staphylococcus aureus and Pseudomonas aeruginosa, and one

pathogenic fungus, C. albicans) [27].

The antimicrobial effect of ethanol, aqueous, and

chloroform extracts of leaf and latex of C. procera were

studied on five bacteria, namely, Escherichia coli, S.

aureus, Staphylococcus albus, Streptococcus pyogenes, and

Streptococcus pneumoniae and three fungi: Aspergillus niger,

Aspergillus flavus, and Microsporum boulardii and one yeast

C. albicans using agar well diffusion and paper disk methods

[28]. 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. The

ethanolic extracts of C. procera latex gave the widest zone of

inhibition (14.1 mm) against E. coli using agar well diffusion

while 9.0 mm was recorded for the same organism in the

disc plate method. The growth of six bacterial isolates was

inhibited by the three extracts except P. aeruginosa and S.

pyogenes that were not inhibited by the aqueous extracts of

both leaf and latex of C. procera. Similarly, the growth of four

test fungi was inhibited by ethanol and chloroform extracts

while the aqueous extract was the least effective on the test

fungi [26].

Anti-inflammatory Activity

The latex (DL) of the plant C. procera has been reported to exhibit

potent anti-inflammatory activity against carrageenan and

formalin that are known to release inflammatory mediators. The

anti-inflammatory effect of aqueous and methanolic extracts of

DL was more pronounced than phenylbutazone (PBZ) against

carrageenan, whereas it was comparable to chlorpheniramine

and PBZ against histamine and prostaglandin E

, respectively.

Both extracts produced about 80%, 40%, and 30% inhibition

of inflammation induced by bradykinin, compound 48/80, and

serotonin. The histological analysis revealed that the extracts

were more potent than PBZ in inhibiting cellular infiltration

and subcutaneous edema [35]. A single dose of the aqueous

suspension of the DL was effective to a significant level against

the acute inflammatory response. The crude DL of C. procera

possesses a potent anti-inflammatory activity [33].

The effect of methanolic dried extract MeDL was compared with

PBZ a non-selective cyclooxygenase (COX) inhibitor, rofecoxib,

a selective COX-2 inhibitor. MeDL of C. procera markedly

reduces cell influx, release of mediators, and oxidative stress

associated with arthritic condition, and therefore, has the

potential to be used as an antiarthritic agent. Chaudhary et al.

reported a protective effect of high molecular weight protein

sub-fraction of latex in monoarthritis rats [28,36].

Larvicidal Activity

C. procera was tested against Anopheles labranchiae mosquito

larvae and exhibited high larvicidal activity with LC

(24 h)

ranging from 28 to 325 ppm [26]. The giant milkweed was

effective in both inhibition of feeding and causing mortality

of larvae. The different rubber-free fractions of the latex were

evaluated against egg hatching, and larval development of the

mosquito Aedes aegypti was found inhibitory effect [27].

The effects of alkaloid extracts of C. procera leaves at the

vegetative stage on the survival of fifth instar larvae and on the

ovarian growth of Schistocerca gregaria have been studied [28].

The toxic effects of crude extracts (both for leaves and flowers)

of C. procera against two species of termites, i.e. Heterotermes

indicola and Coptoter mesheimi were studied [26]. Similarly, C.

procera showed moderate larvicidal effects against second and

fourth instar larvae of the laboratory-reared mosquito species,

Culex quinquefasciatus [25]. C. procera appears to be more

effective than Haloxylon recurvum and Azadiracta indica [26].

Immunomodulatory Activity

Ethanolic extract of the root bark of C. procera was evaluated

for immunomodulatory activity using immunological tests

in mice, humoral mediated antibody titer, delayed-type

hypersensitivity, peritoneal macrophage count, vascular

permeability, hematological profile, i.e. total red blood cell

count, total leukocyte count, % neutrophils and % lymphocytes,

and cyclophosphamide-induced myelosuppression

at three dose levels (50, 100, and 200 mg/kg). The

extract stimulates defense system by modulating several

immunological parameters. Nascimento et al., 2016 discover

immunomodulatory properties of latex protein extracts from

C. procera which protect against experimental infections with

Listeria monocytogenes [37-39].

Wound Healing Activity

Based on its traditional use, C. procera was selected for

evaluation of its wound healing potential in Guinea pigs. 20 μl

of 1.0% sterile solution of the latex of the plant in the animals

was applied topically. The latex significantly augmented the

healing process by markedly increasing collagen, DNA and

protein synthesis and epithelization. Tsala et al. evaluated

Parihar and Balekar: C. Procera: A review

127 TJPS 2016, 40 (3): 115-131

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Part of plant Activity References

Root, latex flowers Analgesic, antinociceptive, antipyretic activity [25,27]

Latex

Plant

Anthelmintic activity

Haemonchus contortus, Schistosoma mansoni,

Rhipicephalus (Boophilus) microplus, Ascaris

[28,26,30]

Latex Antiarthritis and monoarticular arthritis model [2,36]

Root Antiangiogenesis [26]

Flower

Leaf, latex

Antibacterial and antiparasitic antimicrobial activities [2,25,27,28,26]

Latex, root barks Anticancer and in vitro cytotoxicity hepatocellular carcinoma,

skin melanoma, Antitumor studies

[20,21,33-35,41]

Latex Anticonvulsant action [25]

Flowers Anticoccidial activity Eimeria tenella [26]

Latex Antidiabetic, diabetic wound, diabetic nephropathy, diabetic

neuropathy

[28,52,53]

Latex, ariel part Antidiarrheal activity [26]

Whole plant Antieczema, dermatophytic activity [2,40]

Latex Antiedematogenic [2,26]

Root, Flower, Latex Antifertility screening [26]

Leaf Antifilarial activity (Setaria digitata) [2]

Whole plant Antifungal activity (Ceratocystis paradoxa, Candida albicans) [26]

Leaves Antihyperbilirubinemic [2,53]

Leaves Anti-implantation activity [26]

Whole plant Antilithic [54]

Whole plant Antimycoplasmal activity [55]

Latex, root Antioxidant and free-radical scavenging activity [2,25-27,31,32]

Leaf Antiplasmodial activity [2]

Latex Antiseptic - Salmonella enterica s Typ [56]

Latex Antitermites property [26]

Leaves stem Antitussive activity [57]

Root, root bark, leaf, stem, latex Antitumor studies Antiproliferative and cell death (Apoptosis) [25,31]

Latex Allergic contact dermatitis Immunological and allergenic

responses, Immunomodulatory activity

[37-39]

Latex Asthma [35]

Latex Bullous eruption [35]

Latex Cardiotonic action [2,41]

Latex Clot inducing and dissolving properties [58]

Latex Cognition enhancer [59]

Aerial parts Effect on diverse muscles [60]

Latex Enzyme purification potential [25,41]

Latex Enzymatic activity [61]

Latex 5-fluorouracil-induced oral mucositis [62]

Latex, stem bark Gastric ulcers, gastric mucosal protective activity

Anti-Helicobacter pylori and urease inhibition

[2,26-28]

Leaf, flowers Glucose tolerance, hypoglycemic Effect [26]

Latex, flowers Hepatoprotective activity [26]

Latex Hepatorenal functions [63]

Latex Hemorrhagic septicemia or poisoning [26]

Table 2: Various pharmacological activities reported on the plant Calotropis procera

(Contd...)

Parihar and Balekar: C. Procera: A review

128 TJPS 2016, 40 (3): 115-131

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the antioxidant activity and the healing action of the ethanol

extract of C. procera bark against surgical wounds [27,32].

Antiulcer Activity

The antiulcer activity of C. procera using different in vivo ulcer

models was performed. The results of the study revealed that

it significantly inhibited aspirin, reserpine, absolute alcohol,

and serotonin-induced gastric ulcerations in rats and also

protecting the gastric mucosa from aspirin-induced ulceration

in pyloric-ligated rats, and significant protection was observed

in histamine-induced duodenal ulcers in Guinea pigs [26].

Antifertility Activity

The effect of an ethanolic extract of the roots of C. procera was

studied in albino rats to explore its antifertility and hormonal

activities. Strong anti-implantation (inhibition 100%) and

heterotrophic activity was observed at a dose of 250 mg/kg

(1∕4 of LD

). No antiestrogenic activity was detected [26].

Antidiarrheal Activity

The DL of C. procera was evaluated for its antidiarrheal activity.

Like atropine and PBZ, a single oral dose of DL (500 mg/kg) was

produced a significant decrease in the frequency of defecation

and the severity of diarrhea as well as protecting from diarrhea

in 80 % rats treated with castor oil [26].

Estrogenic Functionality

The effects of ethanolic and aqueous extracts of C. procera roots

were studied on the estrous cycle and on some parameters of

estrogenic functionality in rats. Both extracts were found to

interrupt the normal estrous cycle in 60% and 80% of rats

treated [2,26].

Part of plant Activity References

Latex Histaminic activity [2]

Latex Hyperalgesia effect [64]

Leaves Hypotensive [26]

Whole plant Insecticidal activity [2,26]

Latex Interleukin-1beta inducer [2]

Whole plant In‑vitro spasmolytic effect [27]

Leaves Lipolytic, lipoxygenase inhibitors [65,66]

Leaf

Latex

Larvicidal malaria, dengue/dengue hemorrhagic fever and

lymphatic filariasis-Musca domestica, mosquito larvae, Culex

quinquefasciatus say, Aedes aegypti, Anopheles stephensi

[25,26]

Latex Morphogenetic abnormalities [67]

Whole plant Molluscicidal activity [26]

Latex Myocardial infarction [28]

Root Estrogenic functionality [26]

Latex Ontogenetical and histochemical [2]

Aerial parts Purgative [2]

Root, latex, flowers Pro- and anti-inflammatory activities acute inflammation [2,26-28]

Latex Pleurisy [2,25,27]

Latex Proteolytic enzyme activity [61]

Latex Prostaglandins releaser [2]

Arieal part Reproductive potential [68]

Whole plant Schizontocidal activity [2,28]

Latex Toxicity study - Toxic iridocyclitis keratoconjunctivitis. corneal

endothelial cytotoxicity ocular toxicity keratitis cytostatic and

cytotoxic activity, dermatophytes

[25-26,35]

Latex, leaves, bark Wound healing, antikeloidal activity, and surgical wounds [27,32]

Table 2: (Continued)

Figure 1: Photograph of plant Calotropis procera; flowering shoot,

inflorescence, stem, leaves

Parihar and Balekar: C. Procera: A review

129 TJPS 2016, 40 (3): 115-131

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Dermatophytic Activity

Fresh latex of C. procera was screened for antifungal activity

against dermatophytes: Trichophyton spp., Microsporum spp.,

and Epidermophyton spp. The result shows Trichophyton spp.

being the most susceptible followed by the Microsporum spp.

and Epidermophyton spp. were least inhibited [40].

Toxicity Studies

The plant is proven as toxic, and it is one of the plants not

eaten by grazing animals. The latex from the plant has used

by the tribal people to make poison arrows used for hunting

purpose. The latex is highly toxic to human eyes cause ocular

toxicity and produces loss of vision with photophobia. Latex of

C. procera was studied for its inflammatory effects using pedal

edema and air pouch models of inflammation in rats and could

be used to evaluate anti-inflammatory drugs. Furthermore,

latex also produces toxic iridocyclitis, keratoconjunctivitis,

corneal endothelial cytotoxicity, and keratitis when applied

accidentally on the eye.

In a study, DL and flowers of C. procera and its ethanolic

extracts were evaluated against MCF-7 and HeLa cell line

cultures against the MTT assay to determine the inhibitory

effects of test compounds on cell growth in vitro. The standard

drug tamoxifen inhibits 60.46% breast cancer (MCF-7) cells,

whereas the ethanolic extract of DL and flowers showed

cytotoxic properties against both MCF-7 and HeLa cells in a

dose-dependent manner [2,26-28].

CONCLUSION

The plant Calotropis is one of the widely distributed along the

world geographical area. The whole summation of information

about the use of C. procera in the entire world is matched with

available literature. It is well mentioned in the Indian materia

medica; there is broad categorization according to its various

uses in the pharmacological as well as in traditional use. The

literature showed us that it is the plant that is forgotten as

the time passes. Still many scientists have worked to reveal its

phytochemicals and pharmacological activity. The plants are a

rich source of phytoconstituents. Searching new therapeutic

agents is a big challenge for the scientist of the present modern

era and plants are the biggest source of these agents. Screening

of plants for their pharmacological properties with the hope

of finding safe and effective agents is very essential. A large

number of synthetic compounds are available but due to their

environmental pollution and adverse effect on the human

body there use is restricted. To find the safe, effective, and

environmental friendly agent from a plant source, C. procera

is a plant that may present as effective one. In conclusion, the

literature on C. procera suggests a huge biological potential

of this plant. It is believed that the present manuscript may

be useful to provide additional information with regard to its

identification and in accordance to carry out further research

on its use in the treatment of various diseases.

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