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Asian Journal of Biochemical and Pharmaceutical Research Issue 3 (Vol.

1) 2011

ISSN: 2231-2560
Review Article

Asian Journal of Biochemical and Pharmaceutical Research


Tylophora indica:- A review on its ethnobotany, phytochemical and pharmacological
profile.
Suhas Gurav*, Devprakash, G. P. Senthilkumar, Rohan Tembare & Tamiz Mani
Bharathi college of pharmacy, Bharthinagara, K.M.Doodi, Maddur Taluka, Mandya Dist. K.S. India

Received: 4 August 2011; Revised: 21August 2011; Accepted: 28 August. 2011

Abstract: Tylophora indica is an annual or perennial Ayurvedic plant which is used in several traditional
medicines to cure various diseases. Tylophora has increasingly popular for treatment in asthma. These weeds
have been known to possess as, immunomodulatory, hypoglycaemic, urinary diseases, and for its antiallergic
and antimicrobial properties. A wide range of chemical compounds including tyloindicines tylophorinine,
isotylocrebrine, Tylophorine etc. have been isolated from this plant. The presented review summarizes the
information concerning the botany, ethnopharmacology, phytochemistry, biological activity and toxicity of the
Tylophora indica plant.
Key words:- Tylophora indica, ethnopharmacology, phytochemistry

INTRODUCTION:Tylophora indica (Fig.no. 1) (Burm f.)


Merill. (Family: Asclepidaceae) commonly
known as Antmul is a twining perennial plant distributed
throughout southern and eastern
part of India in plains, forests, and hilly places [1]. The plant is found growing normally in Uttar
Pradesh, Bengal, Assam, Orissa, Himalayas and sub Himalayas in India [2]. It is a branching climber
or shrub that grows up to 1.5 meters, leaves are obvate-oblong to elliptic-oblong, 3-10cm long
and 1.5-7cm wide[3]. Roots Long fleshy with longitudinally fissured light brown, corky bark.
Flowers minute, 1-1.5cm across, in 2-3 flowered fascicles in axillary umbellate cymes. Calyx
divided nearly to the base , densely hairy outside; segment lanceolate, acute.
Corolla
greenish
yellow or greenish purple; lobes oblong, acute. Fruit a follicle, up to 7 1cm, ovoidlanceolate,
tapering at apex forming
fine mucro, finally striate, glabrous, Seeds 0.6-0.8 0.3-0.4cm long
[4]. The plant has been reported to contain 0.2- 0.46% alkaloid vizTylophorine, tylophorinine,
tylophorinidine, (+)septicine, isotylocrebrine, tylophorinicine, sterols, flavanoids, wax, resins, and
tannins[5]. The plant has been traditionally used for the treatment of bronchial asthma,
jaundice
[3,6]
and inflammation . Its antitumor, immunomodulatory, antioxidant, antiasthmatic, smooth muscle
relaxant, antihistaminic, hypotensive, antirehumatic activities are scientifically proven. In Ayurveda,
the plant has been used in treatment of asthma , dermatitis and rheumatism [1, 6]. Although the
leaf and root of this plant are widely used for treating jaundice in Northern Karnataka, there
is a paucity of scientific evidence regarding its usage in liver disorder [3]. The other reported
activities
include cytotoxic effect[7] immunomodulatory activity [8], anticancer activity[9] and
antiamoebic activity.[10]

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Chemical constituents:The active constituents of


Tylophoraindica
are
phenanthroindolizidinealkaloids liketylophorine, tylophorinine, tylophorinidine and septidine.
Recently some rare alkaloids namely tyloindicines A, B, C, D, E, F, G, H, I, and J, desmethyltylophorine, desmethyl
tylophorinine, isotylocrebrine, anhydroustylophorinine, anhydrousdehydrotylophorinine, - fagarine, skimmianine, 14- hydroxyisotylocrebrine, 4,6 desmethylisodroxyo Methyltylophorinindine have
been reported. The non-alkaloidal compounds isolated from
Tylophoraindica are kaempferol, quercetin, - and amyrins, tetratriacontanol,
octaosanyloctacosanoate,
sigmasterol,
-sitosetrol, tyloindane, cetyl-alcohol, wax, resin,
coutchone,
pigments, tannins, glucose, calcium salts, potassium chloride, quercetin and
kaempferol. Steam distillation of an alcoholic extract of the air-dried root powder gave p-methoxysalicyaldehyde and a small amount of oilymatter [11].
Phytochemical Studies: The drug Tylophoraindica contains major chemical
constituents
Tylophorine, kaempferol, -amyrin and quercetin, other major alkaloids like
tylophorindine,
desmethyltylophorine,
desmethyltylophorinine,
desmethyltylophoridine,
dehydrotylophorine,
anhydrous dehydrotylophorinine. Other alkaloids (+)-Septicine and (+)-isotylocrebrinefrom fresh leaf
[4]. The new alkaloids include tyloindicines A-E, (+)-14- hydroxyisotylocrebrine and
4-6desmethylisotylocrebrine. Tylophorine, 6- desmethyltylophorine, tylophorindine and5-hydroxy-omethyltylophorindine were the known alkaloids. Structural studies indicate that apart from
tylophorindicneB all alkaloids possess the dibenzo-{f,h} pyrrolo {1,2b} isoquinoline skeleton but
differ in the number, nature and distribution of
the oxygen bearing substituents, in the presence
or absence of C-13a or
benzylic hydroxyls and an angular methyl function. Tylophorine B
possess a cleaved substituted phenanthrene moiety nucleus and an angular methyl group on the
indolizidine portion [12]. Although tylophora alkaloids are structural analogs, their potency of
cytotoxicity, selectivity against NF-kB signaling pathway, and
their
inhibitory
effects
against protein and nucleic acid synthesis are different. Because they dont have an identical spectrum
of targets, the studied are structural but may not be functional analogs [13]. Some structure
showed in table no. 1.
Pharmacological Studies:
Cardiac activity:The hydroalcoholic extract of Tylophora indica (HETI) was screened for
experimentally induced myocardial infarction in rats. Isoprenaline (IPL) is a synthetic catecholamine
and beta-adrenergic agonist that induces severe stress in the cardiac muscle leading to development
of Myocardial infarction. Albino rats were treated with HETI at doses of 100 mg/kg, (HETI-100) or
200 mg/kg (HETI-200) and propranolol 10 mg/kg (PRO-10) for 30 days orally. MI was induced by
subcutaneous administration of isoprenaline (IPL) 150 mg/kg for two consecutive days. Pretreatment
of animals with PRO-10 and HETI-200 provided significant myocardium protection from IPL
damage as indicated by significant decrease in lactate dehydrogenase (LDH) and creatine
phosphokinase-MB (CK-MB) activities in serum and an increase in activities of these enzymes in
heart tissue homogenate (HTH). HETI in higher doses improves the myocardial recovery from injury
induced by IPL. [14]

Antibacterial activity: Antibacterial activity of ethyl acetate and methanol extracts of plant was
investigated by well-diffusion method against bacterial pathogens associated with HIV. The plant
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extracts showed better inhibitory activity against the tested organisms. Methanolic leaf extract of
Tylophora indica showed highest inhibitory activity. The activity showed against the Klebsiella
Pneumoniae, Escherihcia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella
typhi known to be found among the HIV patients.[15]

Hepatoprotectiveactivity: The methanolicextracts of Tylophoraindica leaves was screened for


hepatoprotective activity in carbon tetrachloride induced
hepatotoxicity in albino rats.
Tylophora indica leaves exhibited significantreduction in serum hepatic enzyme when compared to
rats treated with carbontetrachloride alone[16]. The hepatoprotective activity of alcoholic (ALLT)
and aqueous(AQLT) extracts of leaves of Tylophora indica against ethanol-induced hepatotoxicity.
Ethanol induced significant changes in physical, biochemical, histologcal, and functional liver
parameters. Pretreatment with ALLT and AQLT extract significantly prevented the physical,
biochemical, hostological and functional change induced by ethanolin the liver[17].
Lysosomalenzyme inhibiting activity: The
flavone fraction from Tylophoraindicaleaves
showed significant dose dependent lysosomalenzyme inhibiting activity against adjuvant-induced
arthritis at20-50 mg/kg. Flavone fraction showed statistically significant inhibition
of arthritis
lesions (p<0.05) from day 18, (p<0.025)fromday20and(p<0.001)from day 21 onwards in the
adjuvant-induced arthritis studies which was compared to response of standard drug
Indomethacin[18].
Antiallergic activity:The
anti-allergic
effect
of
Tylophora
indica
was
compound with that of disodiumcromoglycolate on perfused rat lung in sensitized rats by
observing the changes in the volume of the perfusate per minute. Administration of aqueous extract
of Tylophora indica and
disodium chromoglycolate during perfusion of sensitized rat lung
significantly increased the rate of flow. The action of Tylophora indica may be due to direct
bronchodilator property and membrane stabilizing and immune-suppressive effects[19].

Diuretic activity:Aqueous and


alcoholic
extracts
of Tylophora indica leaves were
tested for diuretic activity in rats. The aqueous and alcoholic extracts of Tylophora indica leaves
possess good diuretic activity.It is investigated that ethanol is most effective in increasing urinary
electrolyte concentration of all the ions i.e sodium, potassium and chloride followed by chloroform
and aqueous extracts while other extracts did not show significant increase in urinary electrolyte
concentration[20].
Immunomodulatory activity:Studies
with tylophora
alkaloids
had
shown that they inhibit cellular immune response like contactsensitivity to dinitro- flurobenzene and
delayed hypersentivity to sheep red blood cells, in vivo. The alkaloids
mixture suppressed IL-2
production at the lower concentrations.IL- 1production by activated macrophages on the contrary was
doubled in the presence of inhibitory concentration dependent biphasic effect on conA induced
mitogenesis. At lower concentrations they agument con A induced lymphoprolifration by enhancing
IL-2 production. Inhibitory of proliferation at higher concentration of the alkaloids isdue to inhibition
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of IL-2 production and activation of macrophages, which a cytostatic effect[21]. Crude extract of the
leaves of Tylophora indica inhibited delayed hypersensitivity reaction to sheep red bloodcells in rats
when the alkaloid mixture was administered before and after immunization with these cells.
The
alkaloid mixture also inhibited contact sensitivity to dinitrofluorobenzene in mice when given prior
to or after contact sensitization. Lymphocytes taken
from contact sensitized mice,when treated
with tylophora alkaloid invitro and transferred into nave syngeneic hosts, could suppress the transfer
of delayed type hypersensitivity (DTH) response. However, the tylophora alkaloids could not
suppress primary humoral (IgM) immune response to SRBC in mice at the same dose. These studies
suggest that tylophora alkaloids suppress cellular immune responses when administered at any stage
during the immune response[22].
Mastcell stabilisation activity:The total alkaloids of Tylophora indica were tested for mast cell
stabilizing effect I comparision withdisodium cromoglycolate
by challenging against
three
different mast cell degranulators, diazoxide,carbacholandpolymixinB,in- vitro. The results suggest
that tylophora alkaloids may have similar mechanismof action disodium cromoglyacte through cylic
AMP[23].
Anti-Cancer Activity:Tylophorine not only retards the S-phase progression but also dominantly
arrests the cells at G1phase in HepG2, HONE-1, and NUGC-3 carcinoma cells. Moreover,
tylophorine treatment results in down regulated cyclin A2 expression and over expressed cyclinA2
rescues the G1 arrest by tylophorine. Thus, we are the first to report that the down regulated
Cyclin A2 plays a vital role in G1 arrest by tylophorine in carcinoma cells[24].
Anti-Tumor Activity:
Tylophorine analogs
had
an
inhibitory effect on cyclic AMP
response elements, activator protein-1sites, or nuclear factor- kappaB binding site-mediated
transcriptions. In summary, these tylophorine analogs are a unique class of antitumor compounds that
have a mode of action different from known antitumor drugs[25]. Polar phenanthrene-based
tylophorine derivatives (PBTs)
were designed, synthesized and evaluated as potential antitumor
agents. The newly synthesized PBTs were evaluated for cytotoxic activity against the A549 human
cancer cell line. Among them, N-(2,3- methylenedioxy-6-methoxy-phenanthr-9- ylmethyl)-l-2piperidinemethanol and N-(2,3-methylenedioxy-6-methoxy- phenanthr-9-ylmethyl)-5-aminopentanol
showed the highest potency with IC50 values of 0.16 and 0.27M , respectively[26].
Antifeedant along with antimicrobial activity: Crude and pure extracts of Tylophora indica were
investigated in view of antifeedant and antimicrobial activity. Pure compounds displayed strong
antibacterial activity at lower concentrations in all tested bacterial starins except E.coli. while all the
crude and pure compounds showed antifungal
activity against Aspergillusniger, Aspergillus
fumigates and Trichodermavirdae,thepure compounds had strong antifungal activity compared to
Crude extracts[27].
Anti-Asthmatic:A brief exposure of human peripheral leukocytes from asthmatic children to
tylophorine (an alkaloid occurring in Tylophora asthematica) caused the stimulation of adenylcyclase.
This effect was not observed in the leukocytes from the nonasthmatic children or adults [28].
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Plant tissue culture studies:An efficient procedure has been developed for inducing somatic
embryogenesis from mature leaves of Tylophora indica (Burm f.)Merill., and important medicinal
plant. Leaf sections were initially cultured on Murashige and Skoogs(MS) medium supplemented
with thidiazuron(TDZ) in additionwith2,4-dicholorophenoxyacetic (2,4-D), particularly 0.5m TDZ,
along with1.5m2,4Dwasveryeffectivein inducing
somatic
embryos.
Plant
were
regeneratedfromin-vitrosomaticembryos plated onsemisolid medium devoid of growth regulators.
Plantlets were obtained in 65% of the cultures with 2% sodium alginate coated embryos
and
control embryos showed 90% germination[29]. Organogensis callus formulation from mature
leaf peiceswas obtained by using Murashige and Skoog (MS )medium supplemented
with
7M
2,4- dichlorop henoxyaceticacidand1.5M6- benzyladenine. On the medium 92% explants produced
callus. The optimal hormone combination for plantlet regeneration was 8M thidiazaron,
at
which shoot buds were originated from 100% of the cultures, with anaverage of 66. 7 shots
perculture. For roots formation half-strength MS-medium supplemented with 3Mindole3butyricacidwasused.
Plants were transferred to soil,where92% survived after 3 mol of
acclimatization[30]. Another protocol has been developed for high-frequency shoot regeneration and
plant establishment of Tylophora indica from petiole-derived callus. Optimalcallus was developed
from explants on Murashige and Skoog basal medium supplemented with 10M 2,4dichlorophenoxy aceticacid and +2.5M thidiazuron(TDZ). The in-vitro raised plantlets with welldeveloped shoot and roots were successfully established in earthen pots containing garden and soil
and grown in a greenhouse with 100% survival. Four m o n t h s after transfer to pots, the
performance of invitro propagated plants of Tylophora indica was evaluated
on the basis of
selected physiological and compared with exvitro plants of the same age[31].
The effectof
sugars,
gibberellicacid (GA3)andabscisicacid(ABA)onsomatic
embryogenesis from internodalexplant- derivedcallusofTylophoraindica(Burm. f.) Merrill has been
investigated. Embryogeniccalli were produced from internodalex plants and the best result was
achieved by using MS medium supplemented with 4micromol/L 2, 4 Dichlorophenoxy aceticacid(2,4D). Up to 69% of such embryogenic calli differentiated into somatic embryos with
anaverageof25embryosperexplant(per gramofthecalli) on Murashige andSkoog (MS) medium
containing 6micromol/L kinetin (Kn). The study reported here indicates that 200mmol/L sucrose
with 6micromol/LKn,200mmol/Lsucrosewith 10micromol/L GA3 and 200mmol/L sucrose with
2micromol/L ABA significantly improved somatic embryogenesis in T.indica
whereas
glucose
alone or in combination with sucrose had an inhibitory role. The embryos obtained developed
normally and were easily converted into plants [32].
New and efficient transformation system for Tylophora indica using Agrobacterium
rhizogenes strains LBA9402 and A4 to in fect excised leaf and stem explants and intact shoots at
different sites. The induction of callus and transformed roots was dependent on the bacterial
strain, explant type and inoculation site used. Transformed roots were induced only in explants
infected with A. rhizogenes strain A4, while
an optimal transformation frequency of upto 60%
was obtained with intact shoots in oculated at the nodes. Root growth and the production of
tylophorine, the major alkaloid of the plant, varied substantially among the nine root clones studied.
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Both parameters increased over time in liquid cultures, with maximum biomass and
tylophorine
accumulation occurringwithin4-6weeksof growth in fresh medium. Interestingly, in liquid culture, the
culture medium also accumulated tylophorine up to concentrations of 9.78+/-0.21 mg l(-1)[33].To
develop a new micropropagation system for Tylophora indica, an important medicinal plant in ndia,
using root explants as starting material. Root explants cultured on MS medium supplemented
with
6-benzyladenine
(BA)
or
2isopentyladenine
(2iP)
produced
organogenicnodularmeristemoids(NMs) within 4 weeks. Plantlets derived via somatic
embryogenesis and shoot organogenesis were successfully hardened (88-96%) and transferred to the
field[34].Mature leaf explant derived callus of Tylophora indica
(Burm. f.) Merrill yielded
somaticembryos on MS medium supplied with BA(1-2mg/L) orkinetin (1-5 mg/L) or kinetin/BA (12 mg/L) used along with IAA(0.1-1 mg/L). Maximum somaticembryos (30)could be recovered from
100mg of embryogenic callus within 60 days at an optimum concentration of 2 mg/L of BA which
was also best suited for providing the maximum conversion rate (90%) of embryoids to plantlets.
Embryoids from all cultures germinated in the
initiation
medium
and
were
transplanted to sterile vermiculite for hardening. After two weeks of hardening, the plant lets were
transferred to the green house where they grew and established well showing a high rate of surviva
l(90%)[35].
Proto plast culture and plant regeneration of an important medicinal plant Tylophora indica
were achieved through callus regeneration. Protoplast were isolated from leaf mesophyll cells and
culture data densityof5105 protoplast per gram fresh weight, which is required for the highest
frequency of protoplast division (33.7%) and plating efficiency (9.3%). The calli developed shoot buds
after3-4wk, and the frequencies of calli forming shoots varied from 5% to 44%. Optimum shoot
regeneration occurred on MS medium supplemented with 5 MTDZ and 0.4M NAA. On this
medium 44% cultures responded with an average number of 12 shoots per callus. Whole plants
were recovered following rooting of shoots in MS medium supplemented
with 3M indole 3butyric acid [36] .

CONCLUSION:
The scientific research on Tylophora indica suggests a huge biological potential of this plant. It is
strongly believed that detailed information as presented in this review on the phytochemical and
various biological properties of the extracts might provide detailed evidence for the use of this plant in
different medicines. The phytochemical variations and efficacy of the medicinal values of Tylophora
indica is dependent on geographical locations and seasons. Tylophora indica could be further
exploited in the future as a source of useful phytochemical compounds for the pharmaceutical
industry.

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Asian Journal of Biochemical and Pharmaceutical Research

R1
R2
R7

H3CO

R3
H3CO

R4

H3CO
R5

H3CO
R6
Tyloindicine A

OCH3

OCH3

H3CO

H3CO

HO

H3CO
OCH3

OCH3

6- desmethyltyloindicine

Tylophorine

H3CO

H3CO

OH

OH

H3CO

HO
OCH3

Tylophrinidine

HO

OCH3

5- Hydroxy-O- methyltylophorinidine

Table 1: some structure of alkaloids of tylopora indica.[40]

Fig. no. 1 Tylophora indica.


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*Correspondence Author: Suhas Gurav, Bharathi college of pharmacy, Bharthinagara, INDIA

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