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15
A Review on Semecarpus anacardium L.:
An Anticancer Medicinal Plant
T. GOUTHAMAN1, M.S. KAVITHA1, BAKRUDEEN ALI AHMED1,
T. SENTHIL KUMAR2 AND M.V. RAO*
Abstract
Semecarpus anacardium L. is a well known medicinal plant in Ayurvedic
and Siddha medicine. It has been found to have a lot of medicinal Properties,
particularly for its anti-cancerous activity. The present review deals with
distribution, phytochemical and pharmacological aspects of S. anacardium.
Furthermore, the safety evaluation of Siddha preparation of S. anacardium
nut extract has been discussed. Plant improvement studies (seed germination
and in vitro propagation) of S. anacardium are also discussed.
Key words :Semecarpus anacardium, Medicinal plant, Phytopharma-
ceuticals, Anticancer activity, Seed germination, In vitro
propagation
Introduction
Plants have been used in traditional medicine for a long time. About 13,000
plant species have been used as drugs throughout the world and
approximately 25 % of our current materia medica is derived from plants
(Kutchan, 1996). Eighty percent of the world population relies on the plant-
1.Department of Plant Science, Bharathidasan University, Tiruchirapalli 620 024,
Tamilnadu, India.
2.Department of Industry University Collaboration, Bharathidasan University,
Tiruchirapalli 620 024, Tamilnadu, India.
*Corresponding author : E-mail: mvrao_456@yahoo.co.in
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194 RPMP Vol. 19 – Phytopharmacology & Therapeutic Values I
based drugs for their primary health care needs as estimated by World
Health Organization. International market of medicinal plants is over US
$ 60 billion per year which is growing at a rate of 7 %. The herbal drug
market in India is about Rs.644.63 crores and it can be raised to Rs.3000
crores by 2006. The growing demand for plant based medicine, health
products and pharmaceuticals etc. led to the depletion of plant resources.
Hence immediate focus on conservation and sustainable use of medicinal
plants is required.
Semecarpus anacardium L. popularly known as marking nut tree has
many therapeutic applications in Indian system of medicine (Saraf et al.,
1989). Preparations of the nut from S. anacardium were used in ancient
medicine and still find a place in indigenous medicine. Trade in the bhilawa
(S. anacardium) nut is very ancient (King, 1957). Recent reports from all
over the world reveals several scientific studies have been conducted on S.
anacardium to evaluate its medicinal value. The present review summarizes
the phytochemical profile, pharmacological activity and plant improvement
studies of S. anacardium.
Plant description
Semecarpus anacardium is a deciduous tree distributed in Sub-Himalayan
region, tract east of the Beas, ascending to 1050m in Assam (Khasia hills),
Madhya Pradesh, Gujarat, Konkan, Kanara forests of Tamilnadu state
(Gothoskar et al., 1971), Western Peninsula and N. Australia (Kirtikar and
Basu, 1975). It belongs to the family Anacardiaceae. It is commonly called
by various names throughout the country as mentioned below.
Language Common name
English Marking nut tree, oriental cashew
Hindi Bhela, bhilva
Kannada Goddugeru, karigeri, bhallika
Malayalam Ceru, allakkuceru
Sanskrit Bhallatakah, aruskarah
Tamil Senkottai, erimugi
Telugu Bhallatamu, jidi
It is a medium sized to large tree, 15-25 m in height, with grey bark
exfoliating in small irregular flakes (Fig. 1a). Leaves are simple, alternate,
obovate oblong, rounded at the apex, coriaceous, glabrous above and more
or less pubescent beneath, main nerves 15-25 pairs. Flowers are greenish
white fascicled in pubescent panicles (Warrier et al., 1996). Fruits are
obliquely ovoid or oblong drupes and 2.5 cm long. The upper portion of the
fruit is cup-shaped, smooth, fleshy, orange red in colour and sweet and edible
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Semecarpus anacardium Anticancer Medicinal Plant 195
when ripe. It is formed of the thickened disc and accerescent calyx base.
The lower base which may be turned the nut, consists of smooth, black,
shining pericarp which is thick, containing between its outer and inner
laminae oblong cells full of a corrosive resinous juice. This juice is white
when the fruit is immature, but brownish or quite black when the fruit is
ripe. The nut is approximately 1” × 0.75” × 0.33” and weighs on an average
3.5 g (Fig. 1b). The black corrosive juice is largely used throughout the India
as an efficacious drug: internally in the cases of dyspepsia, nervous debility,
acute rheumatism, asthma and cough; externally for swellings, piles and
various cutaneous affections. It is also largely used by dhobis as an indelible
marking ink, and in certain parts of the country an aqueous extract of the
crushed seeds is used in conjunction with iron salts for producing a jet-black
dye on the cloth. Inside the nut and protected by the hard shell is a white
kernel which is sweet and nutritious as the almond or cashew-nut kernel
(Naidu, 1925).
The Nutritive value of unusual food (kernels of S. anacardium), which
is known to be consumed by some populations, was extensively studied
(Ramasastri and Shenolikar, 1974) (Table 1).
The oleic acid content present in the kernel indicated that it could be
used as a good source of salad oil. The marking nut kernels are being used
for consumption especially during pregnancy and lactation because of its
amino acid profile. They can replace the usage of other oil seed because of
its high protein and fat content. However the vesicant nature of bhilwa juice
and manufacturing difficulties of kernels prevents its usage (Ramasastri
and Shenolikar, 1974). If this vesicant nature is abolished, this juice forms
a good source for pharmaceutical industry.
Ayurvedic usage
Ayurveda, literally meaning ‘science of life’, is based on the principle of
subjectivity. It is a well-organized system of traditional health care in large
Table 1. Nutritive value of the marking nut kernel.
Proximate principles Minerals and Essential amino acids
(g / 100 g) vitamins (mg / 100 g) (mg / g protein)
Moisture 3.8 Iron 6.1 Arginine 9.6
Protein 26.4 Phosphorous 836 Histidine 1.8
Fat 36.4 Calcium 295 Lysine 4.1
Fiber 1.4 Thiamine 0.38 Leucine 7.3
Minerals 3.6 Riboflavin 0.17 Isoleucine 4.4
Carbohydrates28.4 Nicotinic acid1.06 Methionone 1.5
Calories 5.87 Threonine 2.1
Phenylalanine 2.5
Valine 4.7
Tryptophan 1.1
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Semecarpus anacardium Anticancer Medicinal Plant 197
parts of the eastern world, especially in India (Chopra et al., 1956).
Ayurvedic medicinal system has identified more than 700 individual herbs,
as well as several complex herbal drug preparations, as useful in the
treatment and/or prevention of diseases including cancer, and improvement
of quality of life of both healthy and diseased individuals (Joseph et al., 1999;
Premalatha 2000; Diwanay et al., 2004). Ayurveda describes S. anacardium
to be a potent drug against a variety of ailments and is popularly known as
Ardha Vaidhya. The fruits and oil have been claimed to be highly efficious
in the treatment of neuritis (Charaka, 1941) and helmintic infection
(Chattopadhayaya and Khare, 1969). S. anacardium has found many
applications in Indian medicine in the treatment of gout and rheumatic pain
(Nadkarni, 1954). The fruits of S. anacardium are subjected to a purification
process before they are used for ayurvedic medicines because they are
considered to be toxic. Purified fruits are claimed to possess rejuvenating
properties, increasing longevity, bringing a glow to the face, sweetness in
tone and improvement in vision (Sreenivasacharyulu, 1931). The fruits of
plants are also largely used in Ayurvedic system of medicine for various
ailments, particularly alimentary tract and certain dermatologic conditions.
It has beneficial action on heart, blood pressure, respiration and neurological
disorders (Kurup et al., 1979, Raghunath and Mitra, 1982, Sharma et al.,
1995). The fruits of S. anacardium are claimed to be useful in treating
leprosy, rheumatoid arthritis, piles, asthma and cough, sexually transmitted
diseases such as syphilis and gonorrhoea, and skin diseases such as
leucoderma (Nadkarni, 1976; Kirthikar and Basu, 1933). The nuts are also
used for management of rheumatisism, wound healing, diabetes and urinary
diseases. It is also used as aphrodisiac, nerve-tonic and as anabolic medicine
in the Ayurvedic system of therapy (Pandey et al., 1967 and Thakur and
Puri, 1978). The chloroform soluble fraction of the whole nut has been
reported to be very useful in the treatment of cancer of oesophagus and
leukemias (Vad and Kulkarni, 1975). The seeds are eaten in certain regions
of India and are considered nutritious. Several Ayurvedic preparations such
as “Bhallataka rasayana”, “Amritha bhallataki” and “Brihat bhallataka
lehya” are marketed in India (Sreenivasacharyulu, 1931).
Phytochemical profile
In alternative medicine, medicinal plant preparations have found
widespread use particularly in the case of diseases not amenable to
treatment by modern methods. A variety of nut extract preparations from
S. anacardium are effective against many diseases viz. arthiritis, tumours,
infections etc (Premalatha, 2000). Understanding the mechanism of the
pharmacological action of S. anacardium can be greatly aided by the
isolation of its active principle and determination of structure and function
relationship. Based on this principle a lot of phytopharmaceuticals from
different parts of S. anacardium have been isolated.
Phytochemical examination revealed 3.85 % of total ash, 0.33 % of acid
insoluble ash, 11.27 % alcohol soluble extractive, 11.84% water soluble
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198 RPMP Vol. 19 – Phytopharmacology & Therapeutic Values I
extractive and 12.71 % moisture content in S. anacardium nuts (Gulati et
al., 1984). Analysis by Bose et al. (1967) revealed the presence of iron, copper,
sodium, calcium and aluminium in traces.
Bhilawanols, isolated from the nut shell of S. anacardium, is a mixture
of 3-pentadec (en) yl catechols unsaturated in the lipophilic side chain. The
chief components of bhilawanol are the 8Z, 11Z-diene (Fig. II1) and 8Z-
monoene (Fig. II2) along with minor amounts of saturated bhilawanol (Fig.
II3) (Nagabhushana et al., 2002). Studies on the methylated Bhilawanol
showed that it contained more than seven components and two major
compounds identified as dimethyl ethers of 1-pentadeca- 8enyl-2, 3-
dihydroxybenzene (Fig. II5) and 1-pentadeca- 7, 10 dienyl-1, 3-
dihydroxybenzene (Fig. II4) (Rao et al., 1973). Reexamination of bhilawanol
showed that it was comprised of two components, 1, 2-dihydroxy-3-
pentadecylbenzene (Fig. III6) and its corresponding diene analogue (Fig. III7)
(Gedam et al., 1974; Cordell and Shin, 1999). Three biflavonoids were
isolated from the ethanol soluble fraction of the S. anacardium nut shells
and characterized as I-4’, II-3’, 4’, I-5, II-5, I-7-hexahydroxy [I-3, II-8]
biflavanone (Fig. III8a), I-4’, II-4’, I-5, II-5, I-7, II-7-hexahydroxy [I-3, II-8]
biflavanone (3’, 8-binaringenin) (Fig. III8b) and I-4’, II-4’, I-7, II-7-
tetrahexahydroxy [I-3, II-8] biflavanone (3’8-billiquiritigenin) (Fig. III8c) (Rao
et al., 1973). The three other biflavonoids, jeediflavanone (Fig. IV9a) ,
semecarpuflavanone (Fig. IV9b), galluflavanone (Fig. IV9c) have also been
isolated from the alcoholic fraction of nut shells and characterized (Murthy,
1983 a; Murthy, 1985 a; Murthy, 1983 b; Murthy, 1983 c; Murthy, 1985 b).
The two other new biflavonoids a dimeric flavonoid nallaflavanone (Fig.
IV10a), semecarpetin (Fig. IV10b) and anacardoflavanone (Fig. IV11) have been
isolated from the nut shells and characterized (Rastogi and Mehrotra, 1999;
Murthy, 1988; Rastogi and Mehrotra, 1995). Ishratullai et al. (1977) isolated
one more biflavonoid namely tetrahydrorobustaflavone (Fig. V12) from the
defatted nuts of the S. anacardium and structure characterized. The leaves
of the S. anacardium found to contain amentoflavone (Fig. V13) as the sole
compound (Ishratullai et al., 1977). The corrosive juice from the pericarp of
the fruit found to contain catechol, fixed oil and anacardol (C18H13O3.COOH)
to which the corrosive properties of the juice are due to two phenolic acids
C16H15O3.COOH and C14H13O3.COOH (Naidu, 1925). From the seeds of S.
anacardium, a new phenolic glucoside, anacardoside, was isolated, and its
structure and configuration were elucidated by a combination of NMR
techniques as-l-O-β-D-glucopyranosyl- (1 → 6) - β -D-glucopyranosyloxy-3-
hydroxy-5-methylbenzene (Fig. V14) (Gil et al., 1995).
Pharmacological activity
Semecarpus anacardium has been used in the treatment of a number of
diseases. A vast number of clinical and pharmacological studies on different
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Semecarpus anacardium Anticancer Medicinal Plant 199
types of Siddha preparations and also on the different parts of S.
anacardium have been carried out.
Siddha preparation of Semecarpus anacardium nut extract
The Siddha preparation of S. anacardium nut extract called Serankottai
nei is being used in the treatment of various ailments. The preparation of
drug Serankottai nei is as follows: S. anacardium nuts, cow’s milk, and ghee
are the main ingredients present in the drug. The drug was prepared by
boiling the nuts (200 g) with 500 ml of milk. After decanting the decoction,
500 ml of milk was added to the boiled nuts and the mixture was again boiled
O
H
R1
R2 1
R1=OH, R2=H
OH
R1
R2 2
R1 = OH, R2 = H
OH
R1
R2 3
R1 = OH, R2 = H
OH
OH
(OH
2
)3Me 4
(OH
2
)
6
OH
OH
(OH )
6
(CH
2
)5Me
5
2
Fig. II. Chemical constituents of Semecarpus anacardium.
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200 RPMP Vol. 19 – Phytopharmacology & Therapeutic Values I
for some time. The decoction was recovered and repeated the process again
with the milk. All the three portions of the milk nut decoction were mixed
with ghee and boiled till dehydrated, filtered and stored. Olive oil was used
as the vehicle for the drug, since it is insoluble in water (Formulary of Siddha
Medicine, 1972).
Anti-inflammatory activity
Semecarpus anacardium nut extract demonstrated significant anti-
inflammatory activity against early phase of acute (carrageen induced), late
phase of chronic (cotton pellet induced granuloma) inflammation and acute
arthritis without any deleterious side effects. The response observed with
the dose level of 150 mg/kg body weight and comparable to 30 mg/kg body
weight of indomethacin. The ability of the drug to reduce the edema
formation may be due to the inhibition of the release of early mediators such
as histamine and serotonin and also due to the inhibition of cyclooxygenase.
S. anacardium decreases the size of cotton pellet granuloma by inhibiting
monocyte infiltration and fibroblast proliferation. It was reported that the
flavonoids present in the nut extract could attribute to the anti-
inflammatory activity (Ramprasath et al., 2004). Ayurvedic drug “Sandhika”
(water extracts of the four plants Commiphora mukul, Boswellia serrata,
Strychnos nux-vomica and S. anacardium) revealed significant anti-
inflammatory activity at a dose level of 0.25 g/kg body weight in carrageen
induced paw edema and cotton pellet induced granuloma of albino rats. It
also showed significant protection against lipid peroxidation. This is
accompanied by reduced glutathione levels and normal serum glutamic
oxaloacetic transaminase (SGOT) and serum glutamic pyruvate
transaminase (SGPT) levels. These findings indicated that “Sandhika” can
be used as a drug for inflammatory disorders and it might be acting through
its free radical scavenging ability (Chaurasia et al., 1995).
Anti-arthritic effect
Semecarpus anacardium nut milk extract was found to be effective against
adjuvant-induced arthritis in albino Wistar rat at the dose level of 150 mg/
kg body weight on the basis of dose dependent study (Vijayalakshmi et al.,
1996). The milk extract of the nut was found to inhibit acute tuberculin
reaction in sensitized rats and also the primary phase of adjuvant arthritis
(Satyavathi et al., 1968 and 1969). A chloroform extract of the nut
significantly reduced acute carrageen induced paw edema in rats and was
active against secondary lesions of adjuvant induced arthritis (Saraf et al.,
1989). Vijayalakshmi et al. (1997a) suggested that the diseased state of
adjuvant arthritis may be associated with augmented lipid peroxidation and
the administration of the drug may exert its anti arthritic effect by retarding
lipid peroxidation and causing a modulation in cellular antioxidant defense
system. The antioxidant property of flavonoids (scavenge singlet O2 and
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Semecarpus anacardium Anticancer Medicinal Plant 201
terminate peroxides by their low redox potential) could augment for the
inhibition of lipid peroxidation (Klopman and Dimayuga, 1988). The effect
of S. anacardium nut milk extract on adjuvant induced arthiritis associated
carbohydrate metabolic changes was evaluated by Vijayalakshmi et al.
(1998). This study indicates that S. anacardium nut milk extract reverted
back the altered level of glycolytic and gluconeogenic enzymes to near
normal levels. S. anacardium nut milk extract treatment brought back
elevated levels of antioxidants (SOD, CAT, GPX, GSH) and the biochemical
markers of inflammation (C-reactive protein (CRP) level and Erythrocyte
sedimentation rate (ESR) to near normal levels in arthritis induced Wistar
rats. The treatment with the drug also significantly reduced paw thickness
and arthritic scores associated with arthritic rats (Ramprasath et al., 2004).
Apart from this, S. anacardium also possess a capability to modulate the
accumulation of neutrophils (Nada et al., 1999) and brings down the
increased levels of lysosomal enzymes (Anderson, 1986) in adjuvant induced
arthritis rats. Apart from this, S. anacardium nut milk extract exerts its
action on adjuvant arthiritis in rats through stabilizing action on lysosomal
membrane and thereby preventing its leakage from lysozomes. This would
prevent the injurious attack to normal tissue and also would tend to retard
amplification and spread of the inflammatory process (Vijayalakshmi et al.,
1997b). All these observations indicated that S. anacardium nut milk extract
is a good therapeutic agent for the arthritis.
Antitumour, Antineoplastic, Cytotoxic and Cytostatic activity
Semecarpus anacardium has been under investigation for its antitumour
properties. A variety of marking nut preparations had been used in clinical
practice and encouraging results have been reported, particularly for cancer
of the esophagus, liver, urinary bladder and leukaemia (Vad, 1973). The
investigation of pericarp oil revealed its anticancer activity (Gothoskar et
al., 1971). The flavonoids present in the S. anacardium nut have the ability
to prevent various cancers (Tumova, 1995). SAN-AB is a chloroform extract
of the whole nut (pericarp and seed) and when administered at a dilution
with peanut oil, it is nontoxic. It showed a differential action on tumour cells
in Yoshida sarcoma (ascites tumour in rats) (Gothoskar et al., 1971). S.
anacardium nut extract revealed potent anticarcinogenic activity against
AFB1 mediated hepatocellular carcinoma. The adverse effects induced by
AFB1 were reversed to near normal levels with reference to biochemical
parameters and histological pattern (Premalatha and Sachdanandam,
1999a). The serum alpha protein level was also brought back to near normal
levels after administration with the S. anacardium nut milk extract. This
provided the additional evidence to use S. anacardium nut milk extract as
an antitumour agent (Premalatha and Sachdanandam, 1999b). The depleted
levels of non-enzymatic antioxidants (uric acid, vitamin C, vitamin E,
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202 RPMP Vol. 19 – Phytopharmacology & Therapeutic Values I
glutathione, total thiol, non-protein thiols, cytochrome P450) were brought
back into normal values followed by the administration of the drug. The
deleterious effects associated with decreased levels of antioxidant are also
controlled by S. anacardium nut extract. Thus S. anacardium nut extract
acts as a potential anticarcinogenic agent against radiation damage caused
by AFB1 induced HCC through its antioxidant property and by the induction
of in vivo antioxidant defence system (Premalatha and Sachdanandam,
1999c). Premalatha et al. (1999) evaluated the influence of the drug S.
anacardium extract on hepato carcinogenicity of aflatoxin B (AFB1) in adult
albino male Wistar rats with reference to tumour marker enzymes (lactate
dehydrogenase, aspartate aminotransferase, alanine aminotransferase,
alkaline phosphatase and γ-glutamyl transpeptidase). Administration of S.
anacardium nut extract resulted in the recoupment of these enzyme levels
to near normal values. The presence of flavonoids in the nut extract is
responsible not only for inhibition of these enzymes (Sanz et al., 1994) but
also possess specific inhibitory action on AFB1-DNA adduct formation and
they reflect their ability to afford protection against development of AFB1—
induced neoplasia in susceptible species (Francis et al., 1989). Bhilawanols,
which was localized maximally in the cell membrane fraction of S.
anacardium extract, could exert its effect through membrane function. The
extract would change the permeability of the membrane, affecting cellular
growth (Patwardan et al., 1988) and this may contribute to its anticancer
property. Premalatha and Sachdanandam (2000a) reported that
anticarcinogenic action by S. anacardium nut extract is possibly via
suppression of AFB1 activation and through interaction with microsomal-
activating components. This is responsible for the chemopreventive ability
of S. anacardium nut extract against HCC. The effect of S. anacardium nut
milk extract on host detoxification system in AFB1 induced hepatocellular
carcinoma was evaluated in male albino rats. It shows that S. anacardium
nut milk extract affords anticancer activity by enhancing both phase I
(cytochrome P450, cytochrome b5, NADPH-cytochrome P450 reductase,
NADH-cytochrome b5 reductase, and aniline hydroxylase) and phase II
(glutathione-S-transferase and UDP-glucuronyl transferase) enzymes to
near normal levels. The anticarcinogenic potency of S. anacardium nut
extract against AFB1-induced hepatocarcinogenesis is mediated through the
induction of hepatic biotransformation enzymes and by enhancing the
oxidative metabolism of a carcinogen (Premalatha and Sachdanandam,
2000b). Stabilizing action on lysosomal membrane and altered glycoprotein
profile exhibited by S. anacardium nut extract could augment for its anti
cancer potency against AFB1 induced hepatocellular carcinoma in male
albino rats (Premalatha and Sachdanandam, 2000c). The antiperoxidative
capacity of the nut extract may play a role in the stabilization of lysosomal
membranes (Premalatha et al., 1997a; Vijayalakshmi et al., 1997a). The
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Semecarpus anacardium Anticancer Medicinal Plant 203
potentiality of chloroform extract of S. anacardium to act as an
antineoplastic agent was proved by its antitumour activity against a wide
spectrum of experimental tumour systems such as leukaemia L1210, P388,
advanced P388, B16 melanoma and glioma 26 (Chitinis et al., 1980; Cassady
et al., 1981). S. anacardium nut extract was found to be effective in
regulating the key enzymes (significant drop in the activity of glycolytic
enzymes [hexokinase, phosphoglu-coisomerase and aldolase] and a
concomitant elevation in the gluconeogenic enzymes [glucose-6-phosphatase
and fructose 1, 6-diphosphatase]) related to carbohydrate metabolism in
dimethyl benzanthracene-induced mammary carcinoma in Sprague-Dawley
rats. Thus S. anacardium nut extract can be a potential antineoplastic agent
against mammary carcinoma (Premalatha et al., 1997b, Sujatha and
Sachdanandam, 2002) and also has a significant role in mitochondrial energy
production (Arathi and Sachdanandam, 2003). Immunological deficiency
(depleted levels of IgG, IgA, IgM, IgI) associated with mammary carcinoma
was brought back to normal levels. This immunomodulatory activity of the
drug could attribute to its potential antineoplastic property (Sachdanandam
and Sujatha, 2001). The cytostatic activity of extracts of S. anacardium had
been reported by various experiments. In one experiment the chloroform
extract of the nuts showed an activity of 150 % T/C in a P388 test system
in mice, at a dose of 50 mg/kg (Gothoskar et al., 1971). In another study a
fraction of the aqueous methanolic extract of the nuts was tested on Eagles
9 KB nasopharynx carcinoma cell cultures, yielding an IC50-value of 2.3
µg/ml. This fraction consisted mainly of pentadecylcatechols. These
pentadecylcatechols however showed no activity on in vivo P388 leukaemia
tests in mice, up to a dose of 80 mg/ml (Hembree et al., 1978). The nuts of
S. anacardium displayed the strongest cytotoxic effect with IC50-values of
1.6 µg/ml (Smit et al., 1995). S. anacardium oil prepared according to the
Ayurvedic principle displayed strong cytotoxic activity in human leukaemia
cell lines. It is surmised that this cytotoxic activity of S. anacardium oil in
human leukaemia cells is attributed to its phenolic constituents, particularly
biflavones (Chakraborty et al., 2004). Semecarpus lehyam (Sowmyalakshmi
et al., 2005) and rasagenthi lehyam (Ranga et al., 2004) which contain S.
anacardium as one of the components can be effectively utilized as
complementary and alternative medicine against breast cancer and prostate
cancer respectively.
Contraceptive agent
Narayan et al. (1985) reported that the water extract of the aerial part of
S. anacardium exhibited a spermicidal activity. The administration of
ethanolic extract of S. anacardium fruit leads to spermatogonic arrest in
albino rats. The significant reduction in the sperm motility and density was
observed. The fruit extract feeding also caused marked reduction in the
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204 RPMP Vol. 19 – Phytopharmacology & Therapeutic Values I
Fig. III. Chemical constituents of Semecarpus anacardium.
number of primary spermatocytes, secondary spermatocytes and
spermatids. The number of mature leydig cells was also decreased and
degenerating cells increased proportionately. These results clearly show the
anti spermatogonic activity of S. anacardium (Sharma and Verma, 2003).
Gudibanda (1968) studied the activity of S. anacardium on the uterus and
ovaries of albino rats. He observed that the cotyledons of S. anacardium
were found to be effective in causing inhibition in both the number litters
(from 12 to 3) and litter size (from 7.17 to 2.67). In the metabolic study he
stated that S. anacardium has a selective action on the gonadotropin effects
on the ovary and also have an antiestrogenic type of action (blockage of
uterine metabolic functions). Murty (1974) observed that no signs of
pregnancy were observed in 8 women patients treated for antifertility effect
of the drug. Oligospermia and azoospermia were observed of the cases
treated for male infertility effect of the drug. This implied that it might be
OH 1
2
OH
8'
9'15'6
OH 1
2
OH
15'7
7'
10'
11'
8'
O
RR
9
65
R
I - A I - C
O
2 1
2'3'
4'
5'
6'
O
RR
R
3
6
R
II - A III - A
O
2
1'
6'5'
4'
3'
2'
I - B
23
3
3
4
1
4
O
8
a. R = R1 =R2 = R4 = OH, R3 = H
b. R = R1 = R2 = R3 = OH, R4 = H
c. R = R3 = OH, R1 = R2 = R4 = H
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Semecarpus anacardium Anticancer Medicinal Plant 205
acting via the hypophysis. From these we can infer that S. anacardium can
be a good oral contraceptive agent.
Lipoxygenase inhibitory activity
Bhilawanol diene present in the bhilawan nut shell liquid was found to be
a potent inhibitor of both soybean and potato lipoxygenases with IC50 values
of 0.85 mM and 1.1 mM, respectively. However, two other compounds
monoene and saturated bhilawanols exhibited relatively lower inhibitory
activity. The unsaturated lipophilic side chain may be an absolute
requirement for inhibitory activity of these compounds and it is proved by
inhibition studies with the synthetic analogues of salicylic acid
(Nagabhushana et al., 2002).
Hypoglycaemic activity
Ethanolic extract of dried nuts (100 mg/kg) of S. anacardium reduced blood
glucose levels of both normal (hypoglycaemic) and streptozotocin-induced
(antihyperglycaemic) diabetic rats. The antihyperglycaemic activity of S.
anacardium was compared with tolbutamide, a sulfonylurea derivative used
in diabetes mellitus (Arul et al., 2004). Kothai et al. (2005) also reported
the antihyperglycaemic activity of S. anacardium against alloxan-induced
diabetes and this was compared with tolbutamide, a sulfonylurea derivative
used in diabetes mellitus. These results clearly indicate the hypoglycaemic
activity of S. anacardium nut extract.
Hypolipidemic and Hypocholesterolemic activity
Semecarpus anacardium nut extract oil fraction at a dose of 1 mg/100 g
body weight significantly reduced serum cholesterol levels and increased
HDL cholesterol levels in the rat fed with atherogenic diet (Tripathi and
Pandey, 2004). The same oil fraction also prevented lipopolysachharide
(LPS) induced nitric oxide (NO) production through its inhibitory activity
on NFκB trascripting factor, which is responsible for the production of
cytokines and other inflammatory factors. Thus it could be a better drug to
treat CHD through mechanism of anti-inflammation, hypolipidemic and
HDL cholesterol enhancing activity. The altered levels of cholesterol and
phospholipids levels were reduced to near normal levels by S. anacardium
nut extract in rabbits fed with athregenic diet. Further it lowered the
elevated levels of LDL-cholesterol and promoted plaques regression (75.3-
83.5 %). This indicated that CHD patients could use it as a potent
antiatherosclerotic drug to halt the progression of atherosclerosis (Sharma
et al., 1995). The evaluation of the antiatherogenic effect of a herbal
formulation, Caps HT2 (methanolic extracts of selected parts of plants,
Commiphora mukul, Allium sativum, Plumbago indica, S. anacardium,
Hemidesmus indicus, Terminalia arjuna, Tinospora cordifolia, Withania
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206 RPMP Vol. 19 – Phytopharmacology & Therapeutic Values I
somnifera and Ocimum sanctum) revealed its antioxidant, anticoagulant,
platelet antiaggregatory, lipoprotein lipase releasing, anti-inflammatory and
hypolipidaemic activity (Mary et al., 2003).
Antimicrobial activity
Alcoholic and oil extracts of S. anacardium dry nuts have antimicrobial
activity against Gram-positive and Gram-negative bacteria (Nair and Bhide,
1996). An Ayurvedic preparation of S. anacardium called “Bhallatakasava”
was shown to have antibacterial activity against tetanus causing
microorganism (Kulkarni et al., 1995). Alcoholic extract of dry nuts showed
dose dependent antifungal activity in vitro against Aspergillus fumigatus
and Candida albicans. At 400 mg/ml concentration, growth of both fungi
were inhibited and considerable reduction in size of cells, hyphae, and
reduced sporulation was also observed (Sharma et al., 2002). Anacardic acid
from the nuts exhibited antimicrobial properties (Chattopadhyaya and
Khare, 1969). Monoene and diene bhilawanols inhibit gram positive
anaerobes but not gram positive anaerobes which is probably due to
lipoprotein layer which prevents penetration of lipophilic agants like
bhilawanols into the cell membranes. Bhilawanols are susceptible to
atmospheric oxidation and complex polymerization in the presence of oxygen
which makes them unable to inhibit aeriobic bacteria (Patwardhan et al.,
1988).
Antistress activity
Immobilization stress caused degeneration (karyorrhexis, membrane
blebbing, chromatin condensation, chromatin fragmentation and
intracellular spacing) of hippocampal neuron cell bodies of rats. Treatment
with S. anacardium nut extract (40 mg/kg/bodyweight) reduced the
degenerating cell bodies (80 %). This indicated that S. anacardium nut
extract has neuroprotective effect and possibly it can be used as an
“antistress” agent in human beings (Shukula et al., 2000).
Other significant properties
The nut extract has direct depressant effects on the isolated frog heart and
rabbit intestine and antagonism to the spasmogenic effects of histamine,
barium chloride and pitocin (Bose et al., 1967). Delayed type of
hypersensitivity induced in mice by sheep red blood cells as an antigen was
potentiated by the nut extract (Gothoskar et al., 1971). Immunomodulatory
potency of the nut extract in hepatocellular carcinoma was also reported
(Premalatha and Sachdanandam, 1998).
Toxic characteristics
Apart from having lot of medicinal properties S. anacardium also found to
have some toxic characters. The powerful irritant properties of the juice of
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Semecarpus anacardium Anticancer Medicinal Plant 207
Fig. IV. Chemical constituents of Semecarpus anacardium.
OOMe
RO
OMe
O
R"O
RO
OR"
R'
MeO
OR"
10
O
RR
8
65
R
AC
O
2
1'
2'3'
4'
5'
6'
R
R
8'' O
R
RO
1"
6"
4"
2"
I - B
23
3"
4
5
7
3
R
5''
6"DF2"
R
6
E
2
1
9
a. R = R3 = R4 = R5 = R6 = OH, R1 = R2 = H
b. R = R2 = R3 = R4 = R6 = OH, R1 = R5 = H
c. R = R1 = R3 = R4 = R5 = R6 = OH,R
2
= H
a. R = OH, R’ = R”= Me, R’’’ = H
b. R, R’, R” = H, R’’’ = Me
OOMe
OH OO
O
O
MeO
OMe
Me
OH
O
O
11
pericarp have frequently been made use of by malingerers in producing
ophthalmic and skin lesions and also in producing abortions (Nadkarni,
1976). Dermatitis occurs in those preparing the oil or in those applying it
to clothing in their capacity as laundryman or in those wearing the marked
clothing. There are two principal patterns of dermatitis (Behl et al., 1966).
Those who use nut preparations medicinally may develop dermatitis of the
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208 RPMP Vol. 19 – Phytopharmacology & Therapeutic Values I
hands and face. If the nuts are ground with a pestle in a mortar held between
the knees, the legs and feet may also be affected. The second clinical pattern
involves those who wear the marked clothing. Exposure to sap of the S.
anacardium led to a development of skin lesions and anuria followed by
diffused cortical necrosis. The mechanism of nephrotoxicity of the sap may
be due to its phenolic consitituents (Matthai and Date, 1979). External
application of S. anacardium lead to the painful micturition and the urine
was reddish and bloody and passing of stools was very painful (Murty, 1974).
Certain side effects were also reported in patients treated with S.
anacardium by Tripathi et al. (1965) and Satyavati et al. (1968). The
occurrence of these side effects was related to the dose of the drug being
administered to the patients in each case (Bajpai et al., 1970). They reported
that 17 patients out of 70 patients developed reactions to the drug. They
usually occur in the form of itching in the dorsal aspects of the hands and
forearm, often associated with reddish maculo-papular rashes in the same
area. There was intense itching and rashes all over the body associated with
stomatitis, burning in the anal region, interfering with sleep of the
individual occurs in severe most cases.
Toxicological evaluation
Semecarpus anacardium can be given orally with milk, ghee, peanut oil etc.
Toxic effects are not observed in such routes of administration. On the
contrary anabolic effects are obtained. Traditional methods recommended
in Ayurveda and Siddha should be closely followed so as to get therapeutic
effects without toxicity (Premalatha, 2000).
Animal studies
Two different studies acute (72 h) and sub acute (30 days) were carried out
on liver and kidney function by a