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Sida cordifolia, a Traditional Herb in Modern Perspective – A Review

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Sida cordifolia, a Traditional Herb in Modern Perspective – A Review

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Sida cordifolia (Malvaceae) is a highly reputable medicinal herb in the Ayurveda and other traditional systems of medicine in India and various other countries. In the Ayurvedic system of medicine it is used as antirheumatic, analgesic, antipyretic, antiasthmatic, nasal anticongestant, antiviral, laxative, diuretic, aphrodisiac, hypoglycaemic, hepatoprotective and in the treatment of Parkinson’s disease. In order to evaluate this traditional plant in a modern perspective, the current review presents essential aspects of S. cordifolia including taxonomy, uses in disciplined traditional medicines, geographical distribution, chemical constituents, pharmacological studies on plant extracts and on single entity constituents, toxicity, and standardization. The chemical composition of this herb comprises of alkaloids, flavonoids, phytoecdysteroids, sterols and fatty acids. The problem of plant misidentification, due to confusion with other related species, is discussed. This paper reviews the conflicting reports regarding the presence or absence of ephedrine and discusses the claimed utility of this herb as a weight loss aid on the basis of ephedrine purported to be present in this species.
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Current Traditional Med icine, 2015, 1, 5-17 5
Sida cordifolia, a Traditional Herb in Modern Perspective
A Review
Ahmed Galal1, Vijayasankar Raman1 and Ikhlas A. Khan1,2,*
1National Center for Natural Products Research, School of Pharmacy, University of
Mississippi, MS-38677, USA; 2Division of Pharmacognosy, Department of
BioMolecular Sciences, School of Pharmacy, University of Mississippi, University,
MS-38677, USA
Abstract: Sida cordifolia (Malvaceae) is a highly reputable medicinal herb in the Ayurveda
and other trad itional systems of medicine in India and various other countries. In the
Ayurvedic system of medicine it is used as antirheumatic, analgesic, antipyretic,
antiasthmatic, nasal anticongestant, antiviral, laxative, diuretic, aphrodisiac, hypoglycaemic,
hepatoprotective and in the treatment of Parkinson’s disease. In order to evaluate this traditional plant in a
modern perspective, the current review presents essential aspects of S. cordifolia including taxonomy, uses in
disciplined traditional medicines, geographical distribution, chemical constituents, pharmacological studies on
plant extracts and on single entity constituents, toxicity, and standardization. The chemical composition of
this herb co mprises of alkaloids, flavonoids, phytoecdysteroids, sterols and fatty acids. The problem of plant
misidentification, due to confusion with other related species, is discussed. This paper reviews the conflicting
reports regarding the presence or absence of ephedrine and discusses the claimed utility of this herb as a
weight loss aid on the basis of ephedrine purported to be present in this species.
Keywords: Ayurvedic medicine, Bala, chemistry, pharmacology, review, Sida cordifolia.
1. INTRODUCTION
Popularly known as bala’, the root of Sida
cordifolia L. (Malvaceae) is regarded as a valuable
drug in the Ayurvedic System of Indian Medicine.
It is also used in the traditional medicine systems
in China, Brazil and other countries for a wide
range of illnesses. The traditional indications of
bala include antirheumatic, antipyretic, analgesic,
antiasthmatic, laxative, diuretic, hypoglycemic, as
a nasal anticongestant [1-3], and as a pain reliever
in sciatica [4]. The root of S. cordifolia has been
recently reported as a potential remedy to reduce
severity of Parkinsonism [5]. Other plant parts,
including the leaves, stems, and seeds are also
employed in traditional medicine for several
medicinal purposes [6]. A number of patented
*Address correspondence to this author at the Division of
Pharmacognosy, Department of BioMolecular Sciences,
School of Pharmacy, University of Mississippi, University,
MS-38677, USA; Tel: 1-662-915-7821; Fax: 1-662-915-7989;
E-mails: ikhan@olemiss.edu; amgalalv@olemiss.edu
herbal formulations disclosed composition with S.
cordifolia as one of their ingredients, for utility as
aphrodisiac, weight reduction aid, health promoter,
particularly immunoenhancing, hepatoprotective,
cardiotonic, and in dental caries prevention
(Table 1).
2. NOMENCLATURE AND BOTANICAL
IDENTIFI-CATION
The nomenclature and botanical identification
of Sida species is often confusing. The source of
the popular Ayurvedic formulation ‘bala’ (meaning
strength in Sanskrit) is ambiguous as different
literatures correlate ‘bala’ to different species of
Sida. While the name ‘bala’ is said to be
traditionally correlated to Sida cordifolia (aka
North Indian bala), S. alnifolia (also known as
South Indian bala) [7] and S. rhombifolia [8], the
name is also shared by several other species of
Sida as well as other unrelated taxa. Sida
cordifolia was reported as the primary source for
bala in Ayurvedic formulations while S. acuta and
2215-0846/15 $58.00+.00 © 2015 Bentham Science Publishers
6 Current Traditional Medicine, 2015, Vol. 1, No. 1 Galal et al.
Table 1. Literature on medicinal uses of Sida cordifolia extracts or purified constituents.
Medicinal properties
Study mo del/
method
Nature of tested material
Plant origin
References
Anti-inflammatory
Rat / in vivo
Ethyl acetate and methanol extract of the ro ot
India
[19]
Anti-inflammatory and analgesic
Mice / in vivo
Aqueous extract of leaves
Brazil
[22]
Analgesic activity
Mice / in vivo
Ethyl acetate extract of the aerial parts and root
India
[19]
Antipyretic and antiulcerogenic
Rat / in vivo
Methanol extra ct of th e aerial parts
India
[49]
Anti-inflammatory, antioxidant,
neuroprotective
Rat / in vivo
Ethanol extract of root
India
[47]
Antinociceptive activity
Mice / in vivo
Chloroform, ethanol, and methanol fractions of the leaves
Brazil
[21]
Vasorelaxation of the rat superior
mesenteric artery, hypotensive action
Rat / in vivo
Aqueous fraction of the hydroalcoholic extract of leaves
Brazil
[50]
Protectiv e effect against mycocardial
infarction
Rat / in vivo
Hydroalcoholic extract of the leaves
India
[52]
Cardioprotection
Rat / in vivo
Hydroalcoholic extract of the leaves
India
[52]
Hypotensive action
Rat / in vivo
Aqueous fraction of hydroalcoholic extract of the leaves
Brazil
[83]
Hepatoprotective
Rat / in vivo
Aqueous extract of leaves
Brazil
[54]
Hepatoprotective
Rat / in vivo
50% ethanolic extract of the root
India
[55]
Sedative effec t CNS depressant
Mice / in vivo
Hydroalcoholic extract of the leaves
[23]
Antioxidant
In vitro assays
Ethanol extract and water infusion of whole plant
India
[4]
Inhibition of lipid peroxidation
In vitro assays
Water infusion of whole plant
India
[4]
Antiproliferative
In vitro on
HepG-2 cells
Methanol extra ct of whole plant
Cameroon
[59]
Antidiabetic
Rat / in vivo
Methanol extra ct and aqueous extract
India
[60]
Hypoglycemic
Rat / in vivo
Methanol extra ct of th e root
India
[19]
Antihypercholestrolemic
Rat / in vivo
Aqueous extract of the aerial parts
India
[60]
Wound healing
Rat / in vivo
Ethanol extract of whole plant
India
[61]
Parkinson’s disease
Rat / in vivo
Aqueous extract of the whole plant
India
[5]
Ant-osteoarthritis
Rat / in vivo
Aqueous suspension of root powder
India
[62]
Analgesic and anti-inflammatory
Mice / in vivo
5`-hydroxymethyl-1`-(1,2,3,9-tetrahydro-pyrrolo [2, 1-b]
quinazoline-1-yl)-hepta-1-one) (9), isolated from the aerial parts
Bangladesh
[85]
Analgesic and anti-inflammatory
Mice / in vivo
3-(3′′,7′′-dimethyl-2′′,6′′-octadiene)-8-C-β-D-glucosyl-kaempferol
3-O-β-D-glucoside (11)
Bangaldesh
[37]
Analgesic and anti-inflammatory
Mice / in vivo
5,7-dihydroxy-3-isoprenyl flavone (9) and 5-hydroxy-3-isoprenyl
flavone (10)
Bangaldesh
[75]
Anti-HIV agent
In vitro assays
and ex vivo
(10E, 12Z)-9-hydroxyoctadeca-10,12-dienoic acid (20), isolated
from the whole plant
South America
[56]
S. rhombifolia are considered as substitutes or
adulterants, on account of similarity of their
alkaloid profiles [9].
Sida cordifolia is widely used in Ayurveda,
Folk, Siddha and Tibetan systems of Indian
medicine. In India, the annual consumption of
Review of the Chemistry and Pharmacology of Sida cord ifolia Current Traditional Medicine, 2015, Vol. 1, No. 1 7
‘bala’ during 2005-06 is estimated to be 5505 MT,
and the raw material is solely sourced from wild
habitats. The raw drug material traded under the
name ‘bala’ includes materials (traded in the form
of roots, seeds and whole plants) obtained from
Sida rhombifolia, S. acuta, S. cordifolia, S.
cordata, etc. [8].
Botanical names such as Sida cordifolia,
S. subcordata, S. caudata, S. cordifolioides and
S. cordata may be confusing to a layman due to
similar specific epithets. Even in the field, an
uninformed gatherer may find it difficult to
distinguish species like S. cordata, S. cordifolia
and S. mysorensis due to their similar leaf and
flower morphology. However, observation of habit
(branches trailing in S. cordata; erect in the other
two species), arrangement of flowers (flowers in
racemes in S. mysorensis; solitary in the others),
features of fruits (mericarps about 10, and fruits
exceeding calyx in S. cordifolia; mericarps about
5, and fruits not exceeding calyx in S. cordata and
S. mysorensis) are helpful in proper identification
of different species of Sida [10, 11]. A study found
that the HPTLC markers of the aerial parts of
S. cordifolia, S. rhombifolia, S. acuta, and
S. cordata were different and thus can be used for
discrimination of these species. The roots of
S. cordifolia, S. acuta and S. cordata can also be
differentiated based on their respective HPTLC
fingerprints. However, the HPTLC profiles of the
roots of S. cordifolia and S. rhombifolia were
indistinguishable [34].
3. TAXONOMY AND DISTRIBUTION OF
SIDA CORDIFOLIA L.
The genus Sida L. (Malvaceae) comprises
about 250 species distributed primarily in the
tropics [12]. The species S. cordifolia is probably
indigenous to Africa, tropical and temperate Asia
and S. America. It is naturalized elsewhere and is
now almost pantropical. Report of this species as
an endangered plant [13] is seemingly not based
on any standard threat assessment or Red Listing
procedures.
Botanical synonyms of Sida cordifolia L.: Sida
herbacea Cav.; S. holosericea Willd. ex Spreng.;
S. hongkongensis Gand.; S. rotundifolia Lam. ex
Cav.
4. MORPHOLOGICAL DESCRIPTION OF
SIDA CORDIFOLIA
Erect herbs or undershrubs, up to 1 m high
leaves ovate, 2-5 × 1.5-4 cm, densely stellate-
hairy, basally 5-7-nerved, base cordate to
subcordate-obtuse, apex subacute to rounded,
margin serrate-crenate; petioles about 3 cm long.
Flowers yellow, about 1.5 cm across, solitary or
fascicled, axillary or terminal. Mericarps, up to 8
mm across; usually 10, 2-awned at apex. Seeds
subreniform, brown [11].
5. USES IN DIFFERENT TRADITIONAL
MEDICINES
In India, S. cordifolia or ‘bala’ is considered to
be one of the most valuable drugs in Ayurvedic
medicine and has been widely used since ancient
times [14]. The roots, leaves, and stems are
utilized as traditional medicines in chronic
dysentery, gonorrhea, and asthma [15]. It is also
indicated for piles, to induce/promote aphrodisia,
and as a remedy for neurodegenerative diseases,
including Parkinson’s disease [16] (Table 1). The
roots of S. cordifolia are administered as a curative
agent for nervous disorders such as facial paralysis
and hemiplegia, as well as in urinary disorders
[17-19]. The root bark is exploited as stomachic,
demulcent, tonic, astringent, bitter, diuretic,
aromatic, and as antiviral agent [16]. The seeds of
S. cordifolia are traditionally used as aphrodisiac
and also indicated in the treatment of gonorrhea,
cystisis, piles, colic and tenesumus. The
pharmacological examination showed that seeds
cause elevation of blood pressure in anesthetized
animals [20]. In Brazil, S. cordifolia is generally
recognized as ‘malva branca’ or ‘malva branca
sedosa’ [21] and is used in Brazilian folk medicine
for the treatment of inflammation of oral mucosa,
asthmatic bronchitis, nasal congestion, blenorrhea
[22], stomatitis, asthma [23, 24] and rheumatism,
and as analgesic [2, 25]. It is also reportedly
indicated in Brazilian traditional medicine as
antirheumatic, antipyretic [26] laxative, diuretic,
anti-inflammatory, analgesic and hypoglycaemic
[19], antiviral [27], antimicrobial [28], and as
aphrodisiac [29]. In China, S. cordifolia is
considered as a herbal equivalent of Ephedra [16],
while in Kenya it is utilized for dental hygiene
[16].
8 Current Traditional Medicine, 2015, Vol. 1, No. 1 Galal et al.
Despite the possible confusion in identification
of Sida cordifolia and other closely related species,
several publications dealing with investigation of S.
cordifolia did not properly verify the botanical
source of the plant material and did not furnish
details of voucher specimens. While study of
incorrectly identified plant could convey wrong
information, the products derived from
misidentified plant material may adversely affect
the safety of the consumers.
6. CONSTITUENTS OF SIDA CORDIFOLIA
6.1. Alkaloids
The roots of S. cordifolia afforded two main
types of alkaloids (Fig. 1); β-phenethylamines
including β-phenethylamine (1), two carboxylated
tryptamines, (S)-(+)-Nb-methyltryptophan methyl
ester (2) and hypaphorine (3), and three
quinazoline alkaloids; vasicine (4), vasicinone (5),
and vasicinol (6), in addition to the bases choline
and betaine found in the water-soluble alkaloid
fraction. Ephedrine was reported in S. cordifolia as
well as allied species [30-34], while other studies
reported the absence of ephedrine [35, 36].
Recently, an unpublished investigation, employing
LC-MS analysis, was conducted on commercial
samples of S. cordifolia and fresh samples of
different parts of S. rhombifolia, concluded the
absence of ephedrine in the examined samples
(Khan, unpublished work). Six-month-old roots of
S. cordifolia produced mainly quinazoline alkaloids.
Two-year-old roots afforded carboxylated
tryptamines as the major components. However, it
was observed that the level of alkaloids in this
plant declines by age [31]. An additional quinazoline
alkaloid, named 5`-hydroxymethyl-1`-(1,2,3,9-
tetrahydro-pyrrolo [2, 1-b] quinazoline-1-yl)-
hepta-1-one) (7) was isolated from the aerial parts
of S. cordifolia, and was reported to possess
analgesic and anti-inflammatory activity in animal
models [37]. The well-known indoloquinoline
alkaloid, cryptolepine (8), is a possible constituent
of S. cordifolia, where it was recently isolated
from this plant [38]. In contrast, a previous study
reported the absence of cryptolepine in S.
cordifolia [39].
6.2. Flavonoids
Two flavones (Fig. 2), namely 5,7-dihydroxy-3-
isoprenyl flavones (9) and 5-hydroxy-3-isoprenyl
flavones (10) [6] and a C-flavonol glycoside
3`-(3``,7``-dimethyl-2``,6``-octadiene)-8-C-β-D-
glucosyl-kaempferol 3-O-β-D-glucoside (11) [40]
Fig. (1). Alkaloids in S. cordifolia. 1: β-phenethylamine; 2: S-(+)-Nb-methyltryptophan methyl ester; 3:
hypaphorine; 4: vasicine; 5: vasicinone; 6: vasicinol; 7: 5`-hydroxymethyl-1`-(1,2,3,9-tetrahydro-pyrrolo [2, 1-b]
quinazoline-1-yl)-hepta-1-one); 8: cryptolepine.
Review of the Chemistry and Pharmacology of Sida cord ifolia Current Traditional Medicine, 2015, Vol. 1, No. 1 9
were isolated from the aerial parts of S. cordifolia.
In a further investigation, three flavonol C-glycosides
were isolated from the same source, these are;
3-(3′′,7′′-dimethyl-2′′,6′′-octadiene)-8-C-β-D-
glucosyl-kaempferol 3-O-β-D-glucosyl[14]-α-
D-glucoside (12), 6-(3′′-methyl-2′′-butene)-3-
methoxy-8-C-β-D-glucosyl-kaempferol 3-O-β-D-
glucosyl [14]-β-D-glucoside (13) [41], in addition
to the previously isolated compound 1.
6.3. Phytoecdysteroids
In contrast to other Sida species, no
phytoecdysteroids were detected or identified in
seeds of S. cordifolia [42]. However, a different
literature source reported the presence of
ecdysteroids in S. cordifolia (Fig. 3), from this
species sidasterone A (14) and sidasterone B (15)
were isolated [43]. A recent publication on
quantification of ecdysteroids in Sida species,
employing LC-UV technique, reported the detection
of 20-hydroxyecdysone (16) and 20-hydroxy-(25-
acetyl)-ecdysone-3-O-β-D-glucopyranoside (17)
in S. cordifolia at levels of 0.001% and 0.003%,
respectively [44]. Taken together, it appears that
the majority of Sida species are either devoid or
contain only low levels of ecdysteroids in their
seeds.
6.4. Steroids and Fatty Acids
The seeds of S. cordifolia contain 30.7% oil, β-
sitosterol and stigmasterol [6], epoxy and
cyclopropenoid fatty acids [45] were isolated from
the seeds. The oil of S. cordifolia afforded mainly
malvalic (18, Fig. 4) and sterculic acids (19, Fig. 4),
along with other fatty acids (C14:0, C15:0, C18:0,
C18:1, C18:2, C18:3) and coronaric acid. Trans
unsaturated lipids were absent. Fresh leaves of S.
cordifolia contain 0.06% essential oil that has a
yellow color and distinguished odor [46]. In a
recent article, bioassay-directed fractionation of
O
OOH
O
OOH
HO
910
O
OOH
HO
OH
O
OH
OH
OH
O
HO
O
OH
OH
OH
HO
OO
OH
HO
OH
O
OOH
HO
OCH
3
OH
O
O
OH
OH
OH
HO
OOH
OH
HO
OH
OO
OH
HO
OH
O
OOH
HO
OH
O
O
OH
OH
OH
HO
OOH
OH
HO
OH
11
12
13
Fig. (2). Flavonoid constituents of S. cordifolia. 9: 5,7-dihydroxy-3-isoprenyl flavones; 10: 5-hydroxy-3-isoprenyl
flavones; 11: 3`-(3``,7``-dimethyl-2``,6``-octadiene)-8-C-β-D-glucosyl-kaempferol 3-O-β-D-glucoside; 12: 3-
(3′′,7′′-dimethyl-2′′,6′′-octadiene)-8-C-β-D-glucosyl-kaempferol 3-O-β-D-glucosyl[14]-α-D-glucoside; 13: 6-(3′′-
methyl-2′′-butene)-3-methoxy-8-C-β-D-glucosyl-kaempferol 3-O-β-D-glucosyl [14]-β-D-glucoside.
10 Current Traditional Medicine, 2015, Vol. 1, No. 1 Galal et al.
the MeOH extract of S. cordifolia led to the
isolation of a hydroxyl unsaturated fatty acid;
(10E, 12Z)-9-hydroxyoctadeca-10,12-dienoic acid
(20, Fig. 4).
7. PHARMACOLOGY
The pharmacological and other biological
effects of Sida cordifolia have been extensively
elucidated to include actions on the cardiovascular
system, CNS, anti-inflammatory, analgesic effect,
hypoglycemic effect, anti-pyretic, anti-ulcerogenic
activity, anti HIV-1 activity, and hepatoprotection.
In a recent animal study on rats, to investigate the
action of ethanolic extract of S. cordifolia root on
quinolinic acid-induced neurotoxicity, S. cordifolia
exhibited neuroprotective, anti-inflammatory and
antioxidative effects comparable to the standard
drug deprenyl. Quinolinic acid is an endogenous
neurotoxin implicated in a number of neurological
disorders, and is used as an investigational tool
[47]. Some of the medicinal properties of Sida
species might be ascribed to the presence of
ecdysteroids [48].
7.1. Anti-inflammatory and Analgesic Effects
The ethyl acetate and methanol extracts of the
root of S. cordifolia, when tested in rats, using the
carrageenan-induced edema model, both produced
anti-inflammatory effects. Nevertheless, the effect
of the ethyl acetate, at a dose of 600 mg/kg, was
equivalent to that of indomethacin. In addition, the
ethyl acetate extracts of the aerial parts and root of
this species exhibited substantial central and
analgesic activity, employing the acetic acid
induced writhing and hot plate methods [19].
In another work [47], the methanol extract of
CH2OH
OH
HO
HO
O
OH CH3
OH
CH2OH
OH
HO
HO
O
OH CH3
OH
OH
OH
HO
HO
O
OH CH3
OH
14 15
16
O
HO HO
OH
HO
OH
OAc
HO
O
O
OH CH3
OH
17
Fig. (3). Phytoecdysteroids of S. cordifolia. 14: sidasterone A; 15: sidasterone B; 16: 20-hydroxyecdysone; 17: 20-
hydroxy-(25-acetyl)-ecdysone-3-O-β-D-glucopyranoside.
20
O
OH
OH
(CH
3
)
7
(CH
2
)
n
CH
4
HOOC
n = 6: Malvalic acid, 18
n = 7: Sterculic acid, 19
Fig. (4). Lypophilic constituents of S. cordifolia, two cyclopropene fatty acids; 18: malvalic acid; 19: sterculic acid;
20: (10E, 12Z)-9-hydroxyoctadeca-10,12-dienoic acid.
Review of the Chemistry and Pharmacology of Sida cord ifolia Current Traditional Medicine, 2015, Vol. 1, No. 1 11
S. cordifolia showed significant antipyretic and
antiulcerogenic properties [49]. An aqueous
extract of S. cordifolia leaves was examined in
animal models for their pharmacological properties
and found to possess anti-inflammatory and
analgesic functions, with low acute toxicity in
mice. Some experimental evidence suggested the
latter effects are mediated via interference with
cyclooxygenase pathways [22].
7.2. Anti-pyretic and Anti-ulcerogenic Activity
A methanol extract of the aerial parts of Sida
cordifolia exhibited a significant anti-pyretic effect
in rats, when tested orally at a dose of 500 mg/kg.
The same extract also showed substantial
antiulcerogenic effects against aspirin and ethanol-
induced ulcers [49]. Chloroform, ethanol, and
methanol fractions derived from an extract of S.
cordifolia leaves were examined for their
antinociceptive effect on orofacial nociception.
The experiments were conducted in mice by using
the glutamate- and formalin-induced orofacial
nociception models. All of the three extracts
exhibited significant antinociceptive activity in the
first and second phases, in the formalin test, while
in the glutamate-induced nociception, only the
chloroform and the methanol fractions showed
significant reduction of nociception [21].
An aqueous fraction obtained from the
hydroalcoholic extract of S. cordifolia, was reported
to induce vasorelaxation of the rat superior mesenteric
artery, in a concentration-dependent relationship,
stimulated for contraction by phenylephrine. It has
been shown that endothelium-derived factors such
as NO, PGI2, and K+ channels are implicated in the
vasorelaxation activity exerted by S. cordifolia that
led to hypotensive action [50].
7.3. Action on Cardiovascular System
In a published study, the influence of a
hydroalcoholic extract of Sida cordifolia leaves on
the biochemical and antioxidant profile of serum/
perfusate and heart tissue homogenate representing
isoproterenol and ischemia reperfusion-induced
myocardial infarction in rats, was evaluated. The
extract of S. cordifolia displayed protective effects
against myocardial infarction. The simultaneous
elevation of the antioxidant enzymes superoxide
dismutase (SOD) and catalase has been recognized
as indication of cardioprotection [51]. Pretreatment
of animals with the hydroalcoholic extract of S.
cordifolia resulted in marked elevation of the
levels of SOD and catalase activity when compared
to the control. The latter action indicated the
ability of S. cordifolia to induce cardioprotection
[52].
Additionally, it was noted in a published study
that the aqueous fraction of an hydroalcoholic
extract of S. cordifolia leaves induced noticeable
hypotension accompanied with intense bradycardia,
when administered to normotensive non-anethetized
rats [53]. The study investigated the mechanism of
action and found that it is possible that the
induction of hypotension and bradycardia might be
attributed to indirect cardiac muscarinic activation
mediated by vagal stimulation, and direct activation
of endothelial vascular muscarinic receptors and
subsequent release of nitrous oxide.
7.4. Hepatoprotective Effect
Sida cordifolia has been reported to possess
experimentally demonstrated hepatoprotective effect.
An aqueous extract of S. cordifolia leaves, orally
administered to rats with partial hepatectomy, at a
dose of 100 mg/kg, was observed to stimulate
hepatic regeneration, through hepatocyte
proliferation. This action was evaluated by
immunohistochemical staining for proliferating
cell nuclear antigen (PCNA), using the PC-10
monoclonal antibody [54]. Orally administered
50% ethanolic extract of the root of S. cordifolia,
displayed substantial hepatoprotective activity
against alcohol-induced hepatotoxicity in rats. The
hepatoprotection was found to be mediated via
reduction of the oxidative stress and down-regulating
the expression of transcription factors. In connection,
the rise in the levels of alcohol intoxication
markers, including alanine aminotransferase, aspartate
aminotransferase, and γ-glutamyltransferase was
quenched after administration of S. cordifolia
extract. Adding to this, the diminished activities of
the antioxidant enzymes and glutathione, due to
alcohol toxicity, were restored after administration
of the extract [55].
7.5. Action on the CNS
The hydroalcoholic extract of the leaves of S.
cordifolia -induced CNS depression in mice,
which was demonstrated as alterations in the
behavior of mice. This effect was also evidenced
12 Current Traditional Medicine, 2015, Vol. 1, No. 1 Galal et al.
from reduction of the motor activity of the
animals, nevertheless, without interfering with
motor coordination [23].
7.6. Anti HIV-1 Activity
From the whole plant of Sida cordifolia, the
compound (10E, 12Z)-9-hydroxyoctadeca-10,12-
dienoic acid (20, Fig. 4) was isolated. This
hydroxyl unsaturated fatty acid was found to be an
exceptional NES (nuclear export signal) non-
antagonistic inhibitor for nuclear export of Rev.
Replication of HIV-1 is essentially dependent on
the regulatory protein Rev or the Rev protein. The
latter is involved in the nucleus-cytoplasm export
of mRNA, which is in turn responsible for
synthesis of the viral proteins necessary for viral
replication. Several analogs of 20 were synthesized
and tested for nuclear export of Rev inhibitory
activity, but the parent compound proved to be the
most potent. Previously, compound 20 was
recognized as a natural anti-HIV agent [56].
7.7. Sida cordifolia in Neurodegenerative
Diseases
In the Ayurvedic system of medicine, the part
which deals with prevention and treatment of
neurodegenerative diseases, such as Parkinson’s,
Alzheimer’s, and loss of memory, is termed
rasayana and the plants having such properties are
known as rejuvenators. Amongst the plants in
rasayana is S. cordifolia which is used clinically in
the treatment of neurodegenerative diseases. It has
been found that these plants (rasayanas) are
generally characterized by possessing strong
antioxidant activity [57]. Free radicals have been
extensively reported to be implicated in
neurodegenerative diseases [58]. Verification of
the antioxidant capacity of S. cordifolia may justify
its indication for treatment of neurodegenerative
diseases in the traditional medicine.
In an in vitro and ex vivo study, the ethanol
extract and the water infusion of S. cordifolia were
examined for their antioxidant properties, utilizing
2,2`-azinobis-3-ethyl-benzothiazoline-6-sulfonic
acid (ABTS) radical cation decolorization assay.
The ethanol extract exhibited significant potency
(IC50 16.1 µg/mL), while the aqueous infusion
showed moderate antioxidant effect (IC50 342.8
µg/mL) [4]. The aqueous extract was also
examined for inhibition of lipid peroxidation and
showed moderate effect with IC50 126.8 µg/mL.
The aqueous extract was tested for toxic action on
viability of PC12 cell line, and it did not display
toxicity [4].
7.8. Antiproliferative and Antioxidant Activities
Methanol extract of S. cordifolia when tested in
vitro on HepG-2 cells, it exhibited significant
antiproliferative activity after 48 h of contact with
the cells. In addition, the same extract was
demonstrated to elevate the activity of the antioxidant
enzymes, superoxide dismutase, catalase, and
glutathione S-transferase after 48 h [59].
7.9. Antidiabetic and Antihypercholesterolemic
Effects
A recently published article described a study
on the effect of methanol and aqueous extracts of
Sida cordifolia on oral glucose tolerance test
(OGTT) in addition to investigating the action of the
aqueous extract on streptozotocin-induced diabetic
rats in comparison with the clinically used drug
metformin. The study revealed that administration
of methanol extract or aqueous extract to normal
rats resulted in reduction of the serum glucose
level on days 7, 14, and 21, in a dose dependent
manner. The maximum decrease in serum glucose
level was observed with the aqueous extract at a dose
of 1 g/kg. When the aqueous extract (1 g/kg, b.w.)
was orally administered in the streptozotocin-
induced diabetic model, a noticeable reduction in
the serum glucose level was observed on days 7,
14, and 21, with concomitant improvement in the
lipid profile, glycogen content, and gain in body
weight [60]. In another account, it was found that
the methanol extract of S. cordifolia root elicited a
substantial hypoglycemic effect, when orally
administered at a dose of 600 mg/kg to rats [19].
7.10. Wound Healing Properties
An ointment made of ethanol extract of Sida
cordifolia was shown to accelerate wound
contraction, and increase tensile strength of
excision, incision and burn wounds in rats. In this
study [61], the parameters indicating wound healing,
including wound contraction, epithelialization
period, hydroxyproline content, tensile strength,
and histopathological features were compared with
the effect of the standard drug, in this case silver
sulfadiazine.
Review of the Chemistry and Pharmacology of Sida cord ifolia Current Traditional Medicine, 2015, Vol. 1, No. 1 13
7.11. Alleviation of Parkinson’s Disease
Symptoms
In a recent investigation, the aqueous fraction
as well as its sub-fractions, including the hexanes,
chloroform and the aqueous ones, were assessed
for their effects on the rotenone-induced biochemical,
neurochemical, histopathological, and behavioral
changes in rat model of Parkinson’s disease.
Rotenone-induced oxidative damage resulted in
elevation in catalepsy and posture instability
accompanied with reduction in rearing behavior.
These signs of the disease were substantially
diminished as a result of co-treatment with
different doses of the aqueous extract (the first
aqueous extract) and the aqueous extract that was
partitioned between hexanes and then chloroform
(the second aqueous extract). Additionally, the
reduction in the level of dopamine in the midbrain
region of the rat was reversed on co-treatment with
the aqueous extracts. The maximum effect was
achieved by the second aqueous extract. As such,
the aqueous fractions of S. cordifolia might be
medicinally useful in treatment of Parkinson’s
disease. This effect is possibly mediated by the
antioxidative properties of the aqueous extracts.
7.12. Influence of Sida cordifolia on
Collagenase-induced Osteoarthritis in Rats
A study [62] was initiated to explore the anti-
osteoartheritic effect of S. cordifolia, on the basis
of its utility in traditional medicine as anti-
inflammatory. S. cordifolia, as a suspension in
water, was orally administered to rats with
collagenase type II-induced osteoarthritis. The
results demonstrated that S. cordifolia possesses
potent anti-osteoartheritic effects. The protective
effects of this medicinal plant on joints was
observed to be stronger than that of Zingiber
officinale (Zingiberaceae). Histological examination
also substantiated the protective properties of S.
cordifolia on synovium and cartilage matrix of the
knee joint in rats.
7.13. Pharmacology of Vasicine and Vasicinone
The pharmacological functions and the toxicity
of vasicine, a respiratory stimulant, have been
elucidated and reviewed to a large extent [63].
Vasicine was originally isolated from Adhatoda
vasica (Acanthaceae) as the major alkaloid at a
level of 0.05-1.11%. In S. cordifolia vasicine content
is close to 0.01%, approximately five times less
than that in A. vasica. At a low concentration, it
evokes bronchodilation of the tracheal muscle,
however, at higher doses it confers protection
against histamine-induced bronchospasm in guinea
pigs [64]. In addition, vasicine is a uterine
stimulant, with properties similar to oxytocin [63,
65, 66]. Vasicinone is an autooxidation metabolite
of vasicine. It was reported to possess in vitro and
in vivo bronchodilatory effects [64, 67], cardiac
stimulatory, and anti-anaphylactic effects [64, 68].
Further, both vasicine and vasicinone demonstrated
anti-inflammatory properties in animal studies
[69].
7.14. Pharmacology of Cryptolepine
Cryptolepine (8), is an indoloquinoline alkaloid,
previously isolated from the West African plant
Cryptolepis sanguinolenta (Apocynaceae), and
was synthesized for the first time in 1906 by
Fichter and Boehringer [70]. Several approaches
for its synthesis have been reported [71-73].
Cryptolepine is an antimalarial agent, inhibitor of
topoisomerase II [74, 75], DNA intercalator, and
possesses substantial cytotoxicity. Despite the
untoward effects of cryptolepine, it holds promise
as an anticancer agent [38, 76], beside
antileishmanial [77], antibacterial activity, and
induction of apoptosis in HL-60 leukemia cells
[78]. Cryptolepine was reportedly isolated from
Sida cordifolia [38]. However, a review of the
literature reveals conflicting reports about the
presence of cryptolepine in S. cordifolia and S.
acuta [39, 79, 80] owing to the uncertainty about
the identity of the plant material used in some of
these studies. This uncertainty of the plant identity
arises from the lack of indications of proper
authentication, or possibly because the plant
material was obtained from unreliable sources.
Recently, cryptolepine, as a DNA intercalator, was
observed to inflict DNA damage in the mammalian
cells, and that may result in genotoxicity [81].
Thus the uncertainty about the presence of
cryptolepine in S. cordifolia makes its safety
questionable and hence consumption of food
supplements that contain cryptolepine as a
component poses a potential health risk.
8. TOXICITY
The aqueous extract of Sida cordifolia was
tested for toxic effect on viability of PC12 cell line
with no signs of toxicity [4]. A further toxicity
14 Current Traditional Medicine, 2015, Vol. 1, No. 1 Galal et al.
study on S. cordifolia was conducted in mice and
was found to be very low, approximately 3g/Kg.
p.o. [82, 83]. The LD50 of the hydroalcoholic
extract of the leaves was determined in mice to be
2.639 g/kg with 90% confidence limits of 2.068-
3.367g/kg, when administered intraperitoneally.
Administration of doses up to 5.0g/kg, was found
not lethal to the animals.
9. STANDARDIZATION
Sida cordifolia has been standardized on the
basis of its bioactive alkaloids visicine and
vesicinone. Reverse phase HPLC and normal
phase HPTLC densitometric methods have been
developed and validated for this purpose. The
HPLC procedure involved using acetonitrile-
phosphate buffer-glacial acetic acid as mobile
phase with UV detection at 300 nm in isocratic
mode. The HPTLC method utilized normal-phase
silica and detection under the UV light at 298 nm
to achieve quantification of these alkaloids as
markers for standardization. In this analysis S.
cordifolia was found to contain vasicine and
vasicinone at levels of 0.011% and 0.0065%,
respectively [84]. In a previous study, an HPTLC
method was described for discrimination between
S. cordifolia and allied species viz. S. cordata, S.
rhombifolia, and S. acuta. The study showed that
the HPTLC fingerprints of the aerial parts of S.
cordifolia, S. rhombifolia, S. acuta, and S.
cordifolia were different, which can be utilized for
discrimination between the four species. The
analysis exhibited that root of S. cordifolia could
be differentiated from the root of S. cordata and S.
acuta by comparing the HPTLC fingerprints of
their extracts. However, the chromatographic
profiles of the roots of S. cordifolia and S.
rhombifolia were indistinguishable [34].
CONCLUSION
Sida cordifolia is prescribed in traditional
medicine in India, China, Brazil and other
countries for a wide range of indications including
bronchitis, asthma, nasal congestion, inflammation
of oral mucosa, rheumatism, neurodegenerative
diseases, chronic dysentery, and gonorrhea.
Additionally, it possesses antiviral, analgesic,
antipyretic, laxative, diuretic, and aphrodisiac
properties, and is also used as a hypoglycaemic
agent. Nevertheless, the presence of ephedrine in
S. cordifolia and in allied species, as the putative
causative agent for many of the medicinal uses of
this herb, has been controversial. Although there
are a number of accounts that provide evidence for
the presence of ephedrine in S. cordifolia as well
as other species, other studies, including in-house
unpublished investigations, have not detected
ephedrine in the examined samples. Therefore,
iniation of thorough studies involving different
species of Sida with a large number of samples
acquired from different geographical regions and
at different plant growth stages, is warranted in
order to confirm the presence or absence of
ephedrine and cryptolepine in the species of Sida.
The existence of a potent bronchodilator-
vasicinone in Sida cordifolia may justify its
therapeutic utility in the Ayurvedic system of
medicine for conditions similar to those treated
with ephedrine. Despite there have been no reports
of toxicity associated with S. cordifolia, the
presence of alkaloids such as vasicine-type
alkaloids and cryptolepine which have not been
adequately evaluated yet, raises concerns about its
safety and possible toxicity. Some of the
exomorphic features of Sida cordifolia are similar
to those of other closely allied species in the genus
and may often be misidentified. It has been
reported that in several cases the market samples
of bala are in fact derived from materials obtained
from various closely allied species, perhaps due to
confusion in the identification. Hence, proper
authentication is mandatory for use of commercial
bala samples in scientific studies and for medicinal
purposes. Adding to this, many of the research
publications do not provide essential details about
plant materials such as the source/origin, details of
collection, method of identification and
information on voucher specimens.
CONFLICT OF INTEREST
The author(s) confirm that this article content
has no conflict of interest.
ACKNOWLEDGEMENTS
This work was supported by the United States
Department of Agriculture, Agricultural Research
Service through Specific Cooperative Agreement
No. 58-6408-2-0009; and partially by Science
Based Authentication of Dietary Supplements
Review of the Chemistry and Pharmacology of Sida cord ifolia Current Traditional Medicine, 2015, Vol. 1, No. 1 15
program funded by the Food and Drug
Administration via grant number 1U01FD004246-
01. Support to Dr. Khan from the Global Research
Network for Medicinal Plants, King Saud
University is also acknowledged.
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Received: May 13, 2014 Revised: August 22, 2014 Accepted: December 16, 2014
... Most of the seed oil of SC contains malvalic, sterculic, and coronaric acids [32]. A methanolic extract of SC containing the hydroxyl unsaturated fatty acid (10E, 12Z)-9-hydroxyoctadeca-10,12-dienoic acid [33]. Antimicrobial activity Human mortality has been dominated by infectious diseases in the recent past. ...
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... 4,5 Secondary metabolite compounds that have been isolated from the genus Sida show antimicrobial, anti-inflammatory, analgesic, hepatoprotective, antiulcer, cytotoxic, cardioprotective, neuroprotective, antitubercular, antioxidant, nephroprotective, antidiabetic and antiobesity activity, abortifacient, and antipyretics. 6,7 Some of the other pharmacological activities are antibacterial and wound healing, and anti-arthritic. 8,9 The chemical constituents of Sida rhombifolia L (Sidaguri) include alkaloid, phenolic, coumarin, tannin, saponin, anthraquinone, terpenoid, cardiac glycoside, steroid, calcium oxalate, phytosteroid, saponin, essential oil, and amino acids. ...
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... Presence of ephedrine has highlighted the utility of this plant. Various pharmacological preparation of this plant has been widely used in asthma diseases, overweight, obesity and as an energy booster, Similarly, used for management of pain, swellings, and heart diseases [12]. ...
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Indigenous system of medicine in Sri Lanka, consist with strong literature evidence and outstanding clinical practice from generation to generation since thousands of years. Most of exceptional information on indigenous system of medical approaches in Sri Lanka was written over ola leave manuscripts. The current study was based on a critical analysis on an indigenous herbal formula that widely used in the management of diabetes mellitus in Sri Lanka. The manuscript is inherited to a tradition of indigenous medicine and granted it from generation to generation. The formula consisted with Aponogeton crispus, Sida cordifolia, Syzygium cumini, Musa paradisiaca, Curcuma Longa and Coscinium fenestratum. antidiabetic, hypoglycemic and hyperglycemic effects including other pharmacological activities were studied. The study revealed that all the ingredients of the formula is highly responsible for the management of diabetes mellitus due to the antidiabetic and hypoglycemic effects of the ingredients. Similarly, all the ingredients were found to have exceptional pharmacological properties which are beneficial in the management of various diseases.
... S. cordifolia is widely used in Indian medicine systems in Ayurveda, Folk, Siddha and Tibet [24] . Usage of S. cordifolia plant in the manufacture of Ayurvedic medicinal products and other herbal medicinal products, supported by scientific evidence, can universally ensure safe and stronger use of natural products [4] . ...
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