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International Journal of Pharmaceutical Sciences and Drug Research 2010; 2(3): 176-181
176
Review Article
ISSN 0975-248X
Phyto-pharmacology of Celastrus paniculatus: An Overview
M. Bhanumathy1*, S. B. Chandrasekar1, Uma Chandur2, T. Somasundaram1
1Natural Remedies Pvt. Ltd., Bangalore, Karnataka, India
2Hillside College of Pharmacy, Bangalore, Karnataka, India
ABSTRACT
Celastrus paniculatus (CP), a traditional Ayurvedic medicinal plant used for centuries as a memory enhancing, anti-
inflammatory, analgesic, sedative and antiepileptic agent. The seed extract has been extensively investigated in several
laboratories for their neuropharmacological effects and a number of reports are available confirming their nootropic action.
In addition, researchers have evaluated the anti-inflammatory, anticonvulsant and other pharmacological effects of CP
preparations/extracts. Therefore, in view of the important activities performed by this plant, investigation must be
continued in the recently observed actions described in this paper. Moreover, clinical studies have to be encouraged, also to
evidence any side effects and possible interactions between this herbal medicine and synthetic drugs.
Keywords: Celastrus paniculatus; Ayurvedic; Medicinal plant; Nootropic action.
INTRODUCTION
Celastrus paniculatus Willd. (CP) belongs to family
Celastraceae is a large, woody, climbing shrub, distributed
almost all over India up to an altitude of 1800 m is known for
its ability to improve memory. [1] It also found in middle and
South Andamans. Ayurveda, the ancient Indian traditional
system of medicine has used this plant seed for prevention
and treatment of various diseases. [2] The bark is
abortifacient, depurative and a brain tonic. The leaves are
emmenagogue and the leaf sap is a good antidote for opium
poisoning. The seeds are acrid, bitter, thermogenic,
emollient, stimulant, intellect promoting, digestive, laxative,
emetic, expectorant, appetizer, aphrodisiac, cardiotonic, anti-
inflammatory, diuretic, emmenagogue, diaphoretic, febrifuge
and tonic, abdominal disorders, leprosy, pruritus, skin
diseases, paralysis, cephalalgia, arthralgia, asthma,
leucoderma, cardiac debility, inflammation, nephropathy,
amenorrhoea, dysmenorrhoea. The seed oil is bitter,
thermogenic and intellect promoting and is useful in
abdominal disorders, beri-beri and sores. [3]
BOTONICAL ASPECTS
Botanical name: Celastrus paniculatus Willd
Family: Celastraceae
Synonym: Celastrus dependens
Vernacular names: Hindi – Malkangani; English – Staff tree;
Kannada – Kariganne; Tamil – Valuluvai; Telugu –
*Corresponding author: M. Bhanumathy, M. Pharm.,
Natural Remedies Pvt. Ltd., Hosur road, Electronic city,
Bangalore, India; Tel.: +91-9986411152
E-mail: bhanugcp@gmail.com, sbchandrasekar@gmail.com
Malkangani.
Botanical description: Celastrus paniculatus Willd. is a
climbing or scrambling shrub, with terete branches; the
young shoots and branches are pendulous.
Leaves – glabrous, broadly ovate or obovate, acuminate or
acute.
Flowers – unisexual, yellowish-green, borne in terminal,
pendulous panicles (flowering throughout the year).
Fruit – capsule, globose, 3-valved, 3-celled, 3-6 seeded.
Seeds are enclosed in complete red arillus, ovoid, brown.
PHYTOCHEMISTRY
Chemical examination of fixed oil from the CP seed showed
presence of fatty acids, viz., oleic, linoleic, linolenic,
palmitic, stearic, crude lignoceric acid, benzoic and acetic
acid as volatile acids. The aqueous extract of CP seed
contained traces of tannins, reducing sugars but no starch. [4]
The petroleum ether extract of husk from the seeds on
saponification yielded palmitic and stearic acids. An
unidentified sterol was obtained from unsaponifiable
fraction. [5]
Several sesquiterpene polyalcohols were reported to be
present in the saponified 80% methanolic extract of seed oil
and malkanguniol is one of the major constituent. Further,
four related alcohols viz., polyalcohol A, polyalcohol B,
polyalcohol C, polyalcohol D were isolated from the extract
along with malkanguniol. [6]
Paraffinic hydrocarbons, β-sitosterol, β-amyrin and a
pentacyclic triterpene diol paniculatadiol were isolated from
the non-sapanifiable fraction of the CP seed oil. The
triterpene diol was assigned structure as olean-12-ene-3β, 29
diol. [7]
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IJPSDR July-September, 2010, Vol 2, Issue 3 (176-181) 177
The fatty acid composition of 4 lipid fractions of CP seed
viz., normal triglycerides (20.2%), polar triglycerides
(44.4%), polar nonglyceridic ester (23.5%) and non polar non
glyceridic ester (11%) was reported. The components
constituting the normal triglycerides were identified as
palmitooleopalmitin, palmitooleostearin, palmitodiolein,
palmitooleolinolein, stearodiolein, triolein and dioleolinolein.
[8]
A new sesquiterpene polyol ester characterized as 1α, 6β, 8β-
triacetoxy-9β-benzoyloxydihydro-beta-agarofuran, along
with the three known compounds: 1α, 6β, 8α-triacetoxy-9α-
benzoyloxydihydro-beta-agarofuran, angulatueoid C, and 1α,
6β, 8β, 14-tetraacetoxy-9α-benzoyloxydihydro-beta-
agarofuran, was isolated from the carbon tetrachloride
(CCl4)-soluble fraction of CP methanolic seed extract. [9]
The fleshy arils of CP on extraction with petroleum ether
yielded a phytosterol designated as celastrol (0.15%), a semi-
solid fat and a resinous colouring matter. [10] The petroleum
ether extract of the fruits showed presence of
steroids/terpenoids, alkaloids and absence of flavonoids and
saponins. [11] A polyalcohol identified as dulcitol was isolated
from the CP flowers. This was the first report of its
occurrence in the genus Celastrus. [12] The ethanol extract of
CP bark showed presence of saponins and tannins and
absence of alkaloids. [13] The petroleum ether extract of the
root bark yielded benzoic acid, n-triacontanol, pristimerin, a
hydrocarbon, an uncharacterized quinine and a golden yellow
oil. [14] Celastrol, pristimerin, zeylasterone and zeylasteral are
identified as quinone-methide and phenolic triterpenoids in
the root outer bark of CP. [15]
A new sesquiterpene ester (Malkangunin) and three
sesquiterpene alkaloids (celapanin, celapanigin, celapagin)
were isolated from CP. The sesquiterpene alkaloids are
derived from a new sesquiterpene tetra-ol (celapanol) which
is alternately esterified with acetic, benzoic, nicotinic and β-
furoic acids. [16] The various mineral elements in the CP plant
was reported as sodium, magnesium, aluminium, potassium,
calcium, vanadium, chromium, manganese, iron, cobalt,
nickel, copper, zinc, molybdenum, silver while strontium and
cerium were found to be absent. [17] The 50% ethanolic
extract of plant (excluding root) showed presence of tannins
(3.52%). [18]
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PHARMACOLOGICAL STUDIES
Central Nervous System
The crude CP seed oil administered orally, intramuscularly
(i.m.) and intraperitoneal (i.p.) in a dose of 1 g/kg produced
sedation in rats. The oil administered orally (100 mg/kg) as
an emulsion showed no sedative effect in rabbits. The same
emulsion (1 g/kg i.p.) to mice produced mild sedation.
Administration of oil (1 g/kg i.m.) to mice showed a
significant reduction of movement. CP seed oil given as
emulsion showed tranquilizing effect on adrenaline and
amphetamine-induced excitement in mice. [24]
The anticonvulsant activity of seed oil was examined against
leptazole, picrotoxin and strychnine-induced convulsions in
rats. It increased strychnine convulsions and reduced
leptazole toxicity. It produced calming effect in injected rats,
potentiated pentobarbitone sedation and exerted
antispasmodic activity with respect to acetylcholine but did
not significantly affect the amphetamine toxicity. [25]
An active fraction, designated as Mal III/A was isolated from
the CP seed oil. It produced a tranquillizing effect on rats,
mice, monkeys and cats in a dose of 200 mg/kg. It
potentiated the effect of hexobarbitone and produced
hypothermia in mice. The fraction also decreased
spontaneous motor activity, amphetamine-induced
hyperactivity, orientation hyperactivity and oxygen
consumption in mice. [26]
Polyester isolated from CP seed oil when given in doses of
35 and 70 mg/kg, i.p. decreased amphetamine-induced
hyperactivity and group toxicity in albino rats. It also reduced
the rectal temperature of rats in both the doses. The analgesic
effect of morphine at 2 mg/kg in rats was significantly
prolonged by the drug in both doses administered 20, 40 and
60 min after injection of morphine. [27]
Oral administration of 1 ml of 5% emulsion of seed oil for 3
days enhanced the learning process in albino rats which was
comparable to that of vasopressin. [28] The memory process
also improved which was more prominent in 7 days treated
animals than in 3 days treated animals. The effects were
comparable to that of vasopressin. [29]
Effects of administration of seed oil on learning and memory
in a passive avoidance model as well as on brain contents of
biogenic amines viz., norepinephrine (NE), dopamine (DA)
and serotonin (5-HT) and their metabolites were studied.
Significant improvement was observed in cognition ability of
the drug treated rats. The drug did not produce any
neurotoxic effect or change in pain threshold in rats. The
contents of NE, DA and 5-HT and their metabolites in the
brain were significantly decreased in the drug treated group.
[30]
The effect of CP seed oil was studied using Morris water
maze apparatus on the 6 day performance of young adult rats.
Chronic oral administration of seed oil (50, 200, or 400
mg/kg) for 14 days completely reversed the scopolamine (0.5
mg/kg)-induced task performance deficit. On the other hand,
acute treatment of CP (200 mg/kg) did not significantly
reverse the scopolamine-induced impairment in maze
performance. Thus, the seed oil of CP, when administered
chronically, selectively reversed the impairment in spatial
memory produced by acute central muscarinic receptor
blockade, supporting the possibility that one or more
constituents of the oil may offer cognitive enhancing
properties. [31]
The aqueous, methanolic, chloroform and petroleum ether
extracts of seeds of CP were investigated for their effect on
cognitive functions in rats. Only the aqueous seed extract
(200 mg/kg, b.w. for 14 days) showed an improvement in
learning and memory in both the shuttle-box and step-
through paradigms. The effect of aqueous seed extract was
also evaluated on oxidative stress parameters and found to
show antioxidant properties by decreasing the lipid
peroxidation and augmenting endogenous antioxidant
enzymes in brain. The aqueous extract of CP (100, 200 and
300 mg/kg for 21 days once a day) was investigated for its
cognitive enhancing and antioxidant propery in model of
alzheimer’s disease in rats. The cognitive behavior was
assessed using passive avoidance and elevated plus maze
paradigms. Estimation of oxidative stress parameters
(malondialdehyde, glutathione, superoxide dismutase and
catalase) was carried out in the whole brain upon completion
of the behavioral task. The aqueous extract of CP was found
to be effective in preventing the cognitive deficits as well as
the oxidative stress caused by ICV streptozotocin in rats. [32]
Enriched forebrain primary neuronal cell (FBNC) cultures
were used to study the neuroprotective effects of three water
soluble extracts of CP seed (CP-WSE) (a room temperature,
WF; a hot water, HF; and an acid, AF) on glutamate-induced
toxicity. Pre-treatment of neuronal cells with CP-WSE
significantly attenuated glutamate-induced neuronal death.
Electrophysiological studies using patch-clamp techniques on
N-methyl-D-aspartate (NMDA)-activated whole-cell currents
in FBNC were conducted to understand the molecular
mechanism of action of CP-WSE. WSE significantly and
reversibly inhibited whole-cell currents activated by NMDA.
The results suggest that CP-WSE protected neuronal cells
against glutamate-induced toxicity by modulating glutamate
receptor function. [33]
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The petroleum ether extract of seeds was evaluated for
antianxiety activity using behavioural disinhibition model of
anxiety in rats. It showed significant inhibition of punishment
related and reward related suppression of operant behaviour
in rats, at dose level of 3.2 g/kg/day for 5 days. [34] The
Celastrus oil, extracted from seeds of CP tested at 2 dose
levels (1 and 1.5 g/kg) in rats exhibited significant anxiolytic
activity and did not produce tolerance. The non-sedative
nature and reversal of anxiolytic property of 5-HT1A partial
agonist buspirone in the open field test point to the
serotonergic mechanism underlying the anxiolysis. [35]
Cardiovascular
The crude CP seed oil administered as emulsion (50-100
mg/kg) produced a gradual fall in cardiac output, bradycardia
and marked increase in pulse pressure on isolated heart lung
preparation in cat. A similar action with 1 g of emulsified oil
was also observed in dogs. [24] The aqueous extract of CP
seed showed 50% angiotensin converting enzyme (ACE)
inhibition; ethanol extract showed mild activity while the
acetone extract was devoid of it. [36]
Antifertility
The seed oil when given in a dose of 0.2 ml/animal/48 h to
adult albino rats for 30 days showed antispermatogenic
effects as evidenced by vacuolization of seminiferous
tubules, germ cell depletion and exfoliation culminating into
an arrest in spermatogenesis. The shrunken tubules revealed
only sertoli cells and spermatogonia in the final stage of
impairment of spermatogenesis. [37] The livers revealed focal
necrosis in animals receiving 0.2 ml (i.p.) seed oil for 30
days, but 45 days post treatment these lesions were absent.
These results indicate that CP oil may have useful
antifertility effects and that the degenerative changes seen in
the liver are reversible with time. [38]
Analgesic and Anti-inflammatory
Flowers of CP and whole plant of Tecomella undulata were
extracted individually in absolute methanol. Using the hot
water tail immersion test in mice and carrageenan induced
paw edema in rats both extracts were tested for their oral
analgesic and anti-inflammatory potentials. Results showed
that CP had both analgesic and anti-inflammatory activities,
while T. undulata had only analgesic potential when
compared with aspirin. [39]
The seed oil showed anti-inflammatory activity in
carrageenan-induced rat paw oedema. The oil in doses of 5
and 10 ml/kg showed 66.60 and 78.78% inhibition of
inflammation as compared to 75.75% shown by 100 ml/kg
dose of ibuprofen. [40]
Hypolipidaemic
Administration of 50% ethanolic seed extract at 500 mg/kg
from day 1 to 120 to hyperlipidaemic rabbits, prevented
accumulation of cholesterol and triglycerides in liver and
aorta and regressed atheromatous plaques of ascending
thoracic and abdominal aorta. The serum cholesterol and
LDL-cholesterol levels were reduced by 60.10 and 71.70%,
respectively. Increased faecal excretion of cholesterol was
observed suggesting that modulation of adsorption was
affected. [41]
Antioxidant activity
The methanolic extract of CP plant was investigated for its
free radical scavenging capacity and its effect on DNA
cleavage induced by hydrogen peroxide UV-photolysis. CP
extract showed a dose-dependent free radical scavenging
capacity and a protective effect on DNA damage in human
non-immortalized fibroblasts. The results indicate that the CP
extract exhibit interesting antioxidant properties, expressed
by their capacity to scavenge superoxide anion and hydroxyl
radical and to reduce the hydrogen peroxide-induced
cytotoxicity and DNA damage in human fibroblast cells. [42]
Three aqueous extracts (WSEs) obtained from CP seeds: a
room temperature extract (WF); a hot water extract (HF); an
acid extract (AF) were investigated for the free radical
scavenging capacity. All the WSEs exhibited a dose-
dependent free radical scavenging capacity for 1,1-diphenyl-
2-picryl-hydrazyl radical (DPPH) and also for superoxide-
generated assays (in vitro assays). All the WSEs significantly
attenuated hydrogen peroxide-induced neuronal death, and
AF was the most effective in protecting the neuronal cells
against oxidative injury caused by hydrogen peroxide (H2O2).
[43]
The superoxide scavenging effects of CP seed oil (CPO) and
two extracts, ethanolic extract (EE) and methanolic extract
(ME), and their neuroprotective effects to H2O2-induced
oxidative stress and glutamate-induced toxicity was
investigated using an enriched neuronal cell culture. CPO
and EE showed dose-dependent, free-radical-scavenging
capacity, but to a lesser degree than observed for ME. The
activity of cellular acetylcholinesterase (AChE) was not
affected by CPO, ME, or EE, suggesting that the
neuroprotection offered by CPO was independent of changes
in AChE activity. Thus data suggest that CPO, ME and EE
protected neuronal cells against hydrogen peroxide-induced
toxicity in part by virtue of their antioxidant properties, and
their ability to induce antioxidant enzymes. [44]
Anti-arthritic activity
The anti-arthritic effect of oral administration of petroleum
ether and alcoholic extracts of CP seed on Freund’s adjuvant
arthritis has been studied in Wistar albino rats. The body
weight loss that was found during the arthritic condition was
corrected on treatment with petroleum ether and alcoholic
extracts of CP seed. The swelling of the paw during the
secondary lesions was also markedly reduced. The results
indicated that the seed of CP is endowed with anti-arthritic
activity. [19]
Wound healing activity
A triterpene compound lupeol isolated from petroleum ether
extract of leaves of CP was screened for wound healing
activity (8 mg/ml of 0.2% sodium alginate gel) by excision,
incision and dead space wound models on Swiss albino rats
(175-225 g). In lupeol treated groups wound healing activity
was more significant than the standard skin ointment
nitrofurazone. Epithelialization of the incision wound was
faster with a high rate of wound contraction as compared
with the control group. In dead space wound model the
weight of the granulation tissue of the lupeol treated animal
was increased indicating increase of collagenation and
absence of monocytes. [45]
Antimalarial
Crude solvent extracts from the root bark and stem of CP
were screened for antimalarial activity against Plasmodium
falciparum using an in vitro culture system. A fraction of the
chloroform extract of the root bark showed the highest
antimalarial activity. An active principle was isolated and
characterized from the chloroform fraction and indentified as
a quinonoid triterpene, pristimerin. When tested in vitro
against various multidrug resistant isolates of P. falciparum,
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IJPSDR July-September, 2010, Vol 2, Issue 3 (176-181) 180
pristimerin was less active than the conventional antimalarial
drugs tested. [46]
Antibacterial
The CP seed oil showed antibacterial activity against
Micrococcus pyogenes var. aureus, Micrococcus pyogenes
var. albus, Micrococcus pyogenes var. citreus, Bacillus
subtilis, Corynebacterium diphtheriae, Salmonella typhosa,
Salmonella paratyphi A and B, Escherichia coli, Proteus
vulgaris, Pseudomonas pyocyana by cup-plate method. The
concentration of oil ranging from 0.4-1% v/v was effective
against Micrococcus pyogenes var. aureus and Salmonella
typhosa. [47]
The oil at different concentrations (20, 40, 60, 80 and 100%)
was tested for in vitro antimicrobial activity against bacteria
Escherichia coli, Staphylococcus aureus, Bacillus cereus,
Salmonella dysentrica, Klebsiella pneumoniae and Proteus
vulgaris and fungi Aspergillus niger, Aspergillus flavus,
Penicillium sp. and Trichoderma sp. The oil showed weak
antibacterial activity in terms of zone of inhibition against
Proteus vulgaris, Staphylococcus aureus and Salmonella
dysentrica at 100% concentration. [42]
The aqueous extract of CP seed showed potent antibacterial
activity against Bacillus cereus, Klebsiella pneumoniae,
Proteus morganii, Proteus vulgaris, Salmonella marcescens,
Salmonella typhosa, Salmonella partyphi A, Escherichia
coli, Pseudomonas aeruginosa, Staphylococcus lutea,
Staphylococcus aureus but was found inactive against
Bacillus subtilis and Salmonella paratyphi B. [48]
Antifungal activity
Twenty-eight South Indian medicinal plants were screened
for their anti-fungal activity against six species of fungi
(Trichophyton mentagrophytes, Trichophyton rubrum,
Trichophyton soudanense, Candida albicans, Torulopsis
glabrata, and Candida krusei). Three plant species extracts,
Celastrus paniculatus, Eriodendron anfractuosum and Ficus
glomerata showed inhibitory activity against 6 species of
fungi. [49]
Acute toxicity studies
CP seed oil was administered orally at a dose of 0.5, 1, 2, 3, 4
and 5 g/kg, b.w. to different groups of rats (n = 8, in each
group). During the first 4 h after the drug administration, the
rats were observed for gross behavioural changes. The
parameters observed were hyperactivity, grooming,
convulsion and sedation, loss of righting reflex, increased
respiration and hypothermia. Celastrus oil administration up
to the highest dose (5 g/kg b. w.) did not produce any toxic
effect on the normal behaviour of the rats. No mortality was
observed even with the highest dose of CP. [30]
The acute oral toxicity study was carried out as per the
guideline set by the Organization for Economic Co-operation
and Development (OECD). One tenth of the medium lethal
dose (LD50) was taken as an effective dose. The LD50 cut-off
dose for petroleum ether extract and alcoholic extract were
found to be 5000 mg/kg and 3000 mg/kg body weight
respectively. Hence, the therapeutic doses were taken as 500
mg/kg and 300 mg/kg body weight for petroleum ether and
ethanolic extracts respectively. [19]
CP, a traditional Ayurvedic medicinal plant has been used for
centuries as a memory enhancing, anti-inflammatory,
analgesic, sedative and antiepileptic agent. The seed extract
has been extensively investigated in several laboratories for
their neuropharmacological effects and a number of
preclinical reports are available confirming their nootropic
action but the exact mechanism of its actions is still
uncertain. It has been suggested that CP, exhibits
neuroprotective and cognitive enhancing effects, in part due
to its, capacity to modulate the cholinergic system and to
contrast oxidative stress. In addition, researchers have
evaluated the analgesic, anti-inflammatory, anxiolytic and
other pharmacological effects of CP preparations/extracts.
Therefore, in view of the important activities performed by
this plant, investigation must be continued in the recently
observed actions. Moreover, clinical studies have to be
encouraged, also to evidence any side effects and possible
interactions between this herbal medicine and synthetic
drugs.
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