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1. Introduction
Immunomodulation is one of the most rapidly developing areas of
medical science & disease
prevention research and has great promises with regard to the
prevention and treatment of a
wide range of disorders such as the inflammatory diseases of
skin, respiratory disorder and
various infectious diseases are disorders caused by organisms
such as bacteria, viruses, fungi
or parasites. And worlds 25.9% of the death occurred due to the
infectious diseases.1 In
addition, infectious diseases are now primarily considered
immunological disorders.
Immunomodulators are natural or synthetic substances that help
regulate or normalize the
immune system. Immunomodulators correct immune systems that are
imbalance. This
elaborate defence system can keep health problems ranging from
HIV/AIDS to the common
cold at bay. Research on immunomodulation by natural products or
synthetic derivatives is of
key interest for immunomodulation therapy for a number of
reasons. Many plant remedies
well-known in traditional medicine or refined natural products
in clinical use by directly
affecting the pathogen. At least part of their effect is
indirect, by stimulating natural and
adaptive defence mechanisms of the host. These findings have now
given many empirical
therapies a rationale, scientific basis and thereby a means for
intelligent improvement. In
discovering the molecular mechanisms by which known remedies
exert their effects, chosen
elements further down the chain of command might be synthesized
and applied directly for
more rapid and selective cure, omitting unwanted side effects.
The direct use of recombinant
cytokines, often in combination with antibiotics, is one
consequence of this rationale.
As herbal immunodulatory drugs has the potential to achieve the
greater efficacious drugs for
the prevention of infectious diseases.
Ayurveda antiquity developed certain dietary and therapeutic
measures to arrest/delay
ageing and to rejuvenate whole functional dynamics of the body
system. This revitalisation and
rejuvenation is known as the rasayan chikitsa (rejuvenation
therapy) which, in the current
context, can be equated to immunomodulation or adaptogenic
activity. Traditionally, rasayana
drugs are used against a plethora of seemingly diverse disorders
with no pathophysiological
connections according to modern medicine. Although this group of
plants generally possesses
strong immunomodulatory activity, only some have been
investigated in detail. In this study,
apart from an insight into the role of Ayurveda and rasayana in
the modulation of the immune
system, immunomodulatory activities of other medicinal drugs,
along with some compounds
isolated from plants are reviewed. Ayurveda physicians believe
in preventive therapy rather
than curative and the rasayanas are the disease-preventive
agents of Ayurveda.2
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Exploring therapeutic Potential of Bhallataka for
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Semecarpus anacardium (SA) Linn. (Family Anacardiaceae),
commonly called as
Bhallatak, It is well-known for its Rasayana properties in
Ayurveda. Immunomodulation using
SA provide an alternative to conventional chemotherapy for a
variety of diseases, especially
when host defence mechanism has to be activated under the
conditions of impaired immune
response or when a selective immunosuppression is desired in
situations such as autoimmune
disorders.3 It appears that the normal way by which the immune
system works is through its
own modulation by factors usually synthesised by the immune
cells.4
SA has been shown; the nut oil from Semecarpus anacardium (SA)
was shown to be
cytotoxic to human leukaemic cell lines.5 The ethyl acetate
extract contains a biflavonoid
known as tetrahydroamentoflavone (THA) that inhibited the enzyme
cyclooxygenase-2 (COX-
2).6 The alcoholic extract of dry nuts had anti-fungal activity
while of nut shells were shown to
prevent lipid peroxidation.7 The nut milk extract is effective
in restoring the fragility of
lysosomal membranes in aflatoxin-induced hepatocellular
carcinoma.8 The immune response
requires timely interplay of multiple cell types within specific
microenvironments to maintain
immune homeostasis. The selectivity and flexibility that is
necessary to regulate cell traffic
under homeostatic and diseased conditions are provided by the
differential distribution and
regulated expression of cytokines and their receptors. As a
consequence, cytokines are
responsible for the development of phenotypes and are,
therefore, logical targets for therapeutic
immune modulation.9
1.1 Classification of immunomodulation
In clinical perspectives, immunomodulators can be classified
into three categories.
Immunoadjuvants are used for enhancing the efficacy of vaccines
and therefore could be
considered to be specific immune stimulants. Adjuvants such as
monophosphoryl lipid A,
immunostimulating complex (ISCOM)10
Immunostimulants are compounds leading predominantly to a
non-specific stimulation of
the immune system and are also called mitogens. These agents,
generally, interact not just
with one but also with other types of immune competent cells,
because of the close link between
the non-specific and specific immune system. This is one
handicap in developing effective
immunostimulating agents without any side-effects, since in some
cases immunostimulants
may also stimulate T-suppressor cells, and thereby reduce the
immune resistance. The terms
immunomodulators or immunoregulators therefore very often seem
to be more appropriate.11
Immunosuppressants are agents that could be used for control of
pathological immune
response in autoimmune diseases, graft rejection, graftversus-
host disease, hypersensitivity
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Exploring therapeutic Potential of Bhallataka for
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immune reaction (immediate or delayed type) and immune pathology
associated with
infections.12
1.2 Immunomodulators in Ayurveda
A significant part of Ayurvedic therapeutics is preventive in
nature. The capacity of the body
to resist disease, is stimulated. The rasayanas of Ayurveda are
believed to be
immunomodulators in modern terminology. Ayurveda considers that
an individual, when
advanced in age, accumulates wastes and toxic substances in
his/her cellular system, which
disrupt the normal metabolism, leading to loss of immunity,
causing disorders or diseases and
finally hastening the ageing process. Ayurvedic experts have
developed various methods to
detoxify the tissues and rejuvenate the body by a special
treatment regimen called rasayana
chikitsa. The immune system is known to be involved in the
aetiology of many diseases as well
as in the pathophysiological mechanisms.
Ayurveda emphasises the promotion of health, a concept of
strengthening host defences
against different, so rasayana drugs are particularly
recommended for the treatment of immune
disorders. The development of agents capable of moving the
patients immune system from a
state of deficiency to one of more normal function would be
likely to have a significant impact
on disease. Such agents would not be a cure but would control
the manifestation and course of
disease some plants and their constituent compounds are claimed
to induce para immunity, the
non-specific immunomodulation of macrophages, granulocytes,
natural killer cells and
lymphocytes and complement functions13. Many studies have been
undertaken to provide
scientific support for the use of rasayana drugs as
immunomodulators and adaptogens.
Rasayana drugs have been reported to treat generalised weakness
14and to afford protection
from cyclophosphamide-induced leukopenia.15
1.3 Concept of 'Vyadhirodhak Chamatav'.
There is a difference in the concept of bodys resistance to
disease in traditional Indian
system of medicine, According to Ayurvedic theory a harmonious
balance between
three humors of the body viz. Vayu', Pitta and Kaph is needed
for positive health; imbalance
of these may cause disease(s). A significant part of Ayurvedic
therapeutics is preventive in
nature. It aims to promote positive health so that individuals
do not suffer from disease. This
is the concept of "Vyadhirodhak chamatav". ie capacity of the
body to resist disease.
Obviously, the immune system. As recognised in modern biology
which provides protection
against microbes, should be a part of it. An entire section of
the Materia Medica of Ayurveda
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Exploring therapeutic Potential of Bhallataka for
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termed Rasaynas' is devoted to enhancement of body's resistance.
Interestingly the
prescribed this section include not only procedures under drugs
('Aushadhi') but also "Aachar"
(daily routine including exercise), "Aahar" (diet and nutrition)
and "Vyavhar (mental attitude
and discipline) which are equally important in achieving the
desired goal. In comparison to this
concept of Rasaynas' in Ayurveda.16
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2. Literature Review
2.1 Classical Text
2.1.1 Charak samhita:
According to charak samhita, chikitsasthanam, the sneha of
bhallatak is taken into one vessel
along with godugdha mulethi is & cooked with the oil. The
same process repeated for 100
times. The uses are generally similar to that of
bhallatakksoudhra
2.1.2 Susruta samhita:
In suhruta Samhita, properties and uses of bhallatak oil
mentioned Bhallatak oil uses are is
bakarak, balya
2.1.3 Shankar nighantu:
In Shankar nighantu, different synonyms like bhallatak ,bhilawa,
bhela, marking
nut,malaccabean, and properties like astringent, hot
,sukarjanan, madhur , and light it is used
in vatalkapha, udarroga, kustha, babascer, sangrahniya, gulam
jawara, agniga, mandya,
krimirog and varann The friuts of ballatak sweet, when ripe,
light,astringent, snigdha, tikana,
hot, chedan, bhedan and appetizer. The bark of fruit is sweet,
light, astringent, and it is used in
deepan, pachan, uderrog, swelling and fever.
Shodan of ballatak: Keep the ripe fruits of ballatak in water,
fruits that are sink into the water,
that take for the shodahan with the same quantity of water, then
rubbed on the brick powder.
2.1.4 Bhav prakash nighantu:
It is a 22-40 feet long tree bark.1 inch thick and grayish in
colour. Flowers are inflorescence
yellowish in colour. Fruits are l inch long, black in colour.
Different properties, chemical
composition and there therapeutics uses and shodahan of
bhallatak mentioned in Bhavpraksh
nighantu.
2.1.5 Nighantu Adarsh:
Bhallatak, aruskar, agnimukh, bhilawa, biladur, veervariksha. It
is astringent, sweet, hot, bitter
and kaphavata nashka. It is a medium size tree. Found in Assam,
madhyabharat and
dakshinabharat. The leafs are long, ovate, Flowers are yellow in
colour.The fruits are heart in
shape, black and white in colour when unripe'
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2.1.6 Raj nighantu:
Bhallatak, agni, dahan, patan, aruskar, anal, krimighan
tailbeej, vaatari, sufoot bijak,
prithakbeej, dhanuurbeej, beejeepadak,etc. Sixteen synonyms are
given. It is katu, tikta, kasaya
in rasa. It is used in vata disorders, udarvikar, anaah and
parmeha. The fruits of bhallatak are
madhur rasa in and ushna. It is used in kapha, sarram, swasarog,
annah, vibandsool, udarrog
and kriminashak
2.1.7 Dhanvantari nighantu:
Aruskar, dahan, tapan, agnik, bhallatak, agnimukha, virtaru and
dhanu. It is katu tikta, madhur,
ushna virya, krimighan and vata, pitta nashak
2.1.8 Priya nighantu:
Bhallatak is sharp like bhala weapon. It cause irritation when
touch the fruit without precaution.
It is used in kusta, arsha, kapharog, raktadustijanya vikar,
agnimandya, krimiroga.
2.1.9 Dravyaguna Vijnana:
Botanical description: A moderated size deciduous tree,
exudation a dark juice. Young
branches inflorescence petiole and under side of leafs
pubescent. Leaves- oblong, ovate
rounded at apex, cartilaginous at margin, very coriaceous.
Flowers- fasciculate, arranged in
erect, compound greenish yellow colour. Fruits drupes, obliquely
oval or long, smooth, shining,
purplish-black when ripe, cup orange. Flowering round the year,
mostly during May-June,
fruits ripe from November to February.17
2.1.10 Ayurvedic pharmacology:
Class: Kushthaghna, Deepaniya, Mootrasangrahaniya, Nyagrodhadi,
Mustadi
Kula: Amra kula
Family: Anacardiacee (Ana-like, Cardium-heart)
Method of purification: Take out the bhallataka fruit along with
the stalk and keep it in the
powder of bricks for period of one week. Clean and wash
thouroughly by a rubbing it, then
boil it with milk. This purifies bhallataka impure bhallataka
act as a toxin, hence it should be
used without purifies. Small children, pregnant not women, older
people, persons having
pittaprakruti, patients having tendency to bleed, and those who
are allergic to Bhallatak should
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Exploring therapeutic Potential of Bhallataka for
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not take bhallataka. It is important for a vaidya to know the
contraindication rather than the
indication of bhallataka18
2.1.11 Ayurvedic pharmacopeia of India:
Bhallataka consists of mature fruit of Semecarpus anacardium
Linn. (Fam.Anacardiaceae), a
medium sized tree found in moist deciduous forests all over the
country.
Synonyms
Sanskrit : Bhallatakam
Assamese : Bhelaguti
Bengali : Bhela
English : Marking Nut
Gujrati : Bhilam
Hindi : Bhilawa
Kannada : Bhallataka
Malayalam : Chera
Marathi : Bibba
Oriya : Bhollataki, Bholai
Punjabi : Bhilawa
Tamil : Tatamkottai, Scramkotati
Telugu : Nallajidi, Nallajidiginga
Urdu : Baladur, Bhilavan
Description
Macroscopic: Fruit laterally flattened, drupaceous, dark brown,
nut 2.5-3 cm long, obliquely
ovoid, smooth, shining with residual receptacle.
Microscopic:
Fruit - Pericarp differentiated into epicarp, mesocarp and
endocarp; in longitudinal section
pericarp shows outer epicarp consisting of single layer of
epidermal cells which are elongated
radially and lignified, characteristic glands found in pericarp
which exude oil globules and arise
as small protuberances in epicarp and due to pressure exerted by
cells of mesocarp, some of
epidermal cells and cuticle rupture and oil globules exude from
oil glands; mesocarp a very
broad zone, 30-40 layers thick, composed mostly of
parenchymatous cells having lysigenous
cavities and fibro-vascular bundles, below epidermis a few outer
cells of parenchyma smaller
as compared to rest; rosette crystals of calcium oxalate found
scattered in parenchymatous
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Exploring therapeutic Potential of Bhallataka for
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cells, some cells get dissolved and form lysigenous cavities
which increase in size with maturity
of fruit, cavities do not have any special lining and contain an
acrid and irritant yellowish oily
secretion; endocarp consists of two distinct layers, innermost
prismatic, very much elongated
radial walls, being highly thickened, outer layer shorter and
thinner than prismatic layer but
cells similar to the former; number of mesocarp parenchyma
contain rosette crystals of calcium
oxalate and oil drops in oil glands; lysigenous cavities of
mesocarp contain oily vesicating
substance, insoluble in water and soluble in alcohol, ether,
chloroform. Powder - Dark-brown;
shows rosette crystals of calcium oxalate and oil globules.
Identity, Purity and Strength
Foreign matter : Not more than 1 %
Total Ash : Not more than 4 %
Acid-insoluble ash : Not more than 0.5 %
Alcohol-soluble extractive : Not less than 11 %
Water-soluble extractive : Not less than 5 %
Constituents: A Tarry Oil containing Anacardic Acid,
Non-Volatile Alcohol (Cardol).
Properties and action
Rasa : Madhura, Katu, Tikta, Kasaya
Guna : Laghu, Snigdha,Tiksna
Virya : Usna
Vipaka : Madhura
Karma : Dipana, Kaphahara, Pacana, Vatahara, Chedi, Bhedi,
Medhya
Important formulations: Amrta Bhallataka Leha, Bhallataka
Rasayana, Bhallatakadi Modaka
Therapeutic uses: Arsa, Anaha, Grahani, Gulma, Krimi,
Kustha.
Dose: 1.2 g. of the drug in Ksirapaka form.19
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2.2 Reported pharmacological activities of Semecarpus
anacardium.
Table 1: Reported pharmacological activities of SA
S.
No
.
Extract/
Formula
tion
Pharmacological
activity reported
In vivo
models
(Humans/An
imals)
In vitro
models (cell
lines/
chemical or
microbial
assay)
Dose Ref
1 Nut
extract
Breast cancer - T47D cell
line
400
mg/mL
20
2 Seeds
(Biflavan
oids)
COX inhibitors Male spargue
Dawley rats
(Rat paw
edema assay)
- 100 g/kg 21
3 Nut milk
extract
Antidiabetic Male albino
wistar rats
- 300 mg/kg
b.wt. (For
21 days)
22
4 Nut
extract
Antiarthritic Male albino
wistar rats
- 150 mg/kg 23
5 Nut milk
extract
Antiarthritic Male albino
wistar rats
- 150 mg/kg 24
6 Nut
extract
Immunomodulato
ry and
Antiarthritic
Humans - 1g/mL 25
7 Nut milk
extract
Antiarthritic Male albino
wistar rats
(Freunds adjuvant
induced
arthritis)
- 150 mg/kg 26
8 Chlorofo
rm
extract
of SA
Aphrodisiac Male albino
wistar rats
- 150 and
300 mg/kg
27
9 Ethanol,
acetone
and
aqueous
extract
Antioxidant - DPPH and
ABTS assay
100
g/mL
(DPPH
assay) and
0.01 to 0.5
mg/mL (
ABTS
assay)
28
10 Nut milk
extract
Antidiabetic (type
II)
Male spargue
Dawley rats
(Streptozotoc
in induced
- 200 mg/kg 29
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diabetes
mellitus)
11 Fruit
extract
Hepatoprotective Male albino
wistar rats
- 250 and
500
mg/kg
30
12 Methano
lic
extract
Anti fungal - Fungal
strains
( Fusarium
oxysporum,
Rhizctonia
solanii,
Alternaria
spp., and
Sclerotium
rolfsii)
6.25,12.5,
25, 37.5,
50 and
62.5
g/mL)
40
13
Petroleu
m ether
nut
extract
Antibacterial - Microorganis
m
(E.Coli,Bacill
us
subtilis,Micro
coccus
luteus,Klebsi
ella
pneumonia,
Streptococcu
s
aureus,Proteu
s vulgaris,
Salmonella
typhi)
150 l
40
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14 Aqueous
and
organic
extract
Antimicrobial - Microorganis
m
(Staphylococ
cus aureus,
Shigella
flexneri,
Bacillus
licheniformis,
Vibiro
cholera,Pseud
omonas
aeruginosa,
Streptococcu
s aureus,
Bacillus
brevis.)
10,50,100
mg/ml
10mg
G/ml
31
Ayurvedic formulation.
15 Amrut
Bhallata
kavaleha
(Electuar
y)
General tonic and
vitalizer
Humans - 1 to 2
teaspoonfu
l for 2
times
32
16 Bhallata
kasava
(Wine)
Neuralgia and
asthma
Humans - 2 to 4
teaspoonfu
l for 2
times
41
17 Suran
vatak
(Pills)
Piles and
anorectal diseases
Humans - 2 pills
(500 mg
pill) for 2
times
41
18 Sanjeeva
ni Vati
(Pills)
Dysentry and
diarrhea
Humans - 2 pills
(250 mg
pill) for 3
times
41
19 Bhallata
k Parpati
(Powder)
Rheumatic
diseases
Humans - 250 mg
for 3 times
41
20 Narsimh
a
Choorna
(Powder)
General
restorative
Humans - 1 to 2 gm
for 2 times
41
2.3 Various Antidotes of SA Toxicity
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Exploring therapeutic Potential of Bhallataka for
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Cows milk, Cows Urine is recommended as the antidote for
bhallataka blisters. Neem is used
as topical Antidotes.33
2.4 Drug interaction of SA
2.4.1 Manodeep Chakraborty et al., 2010 have reported
Interaction of Semecarpus
anacardium L. with propranolol against isoproterenol induced
myocardial damage in
rats
With a view to evaluate the cardio protective effect of
ethanolic extract of S. anacardium nut
and the possible interaction with propranolol against
isoproterenol induced myocardial damage
in rats, female Sprague-Dawley rats were pre-treated with
propranolol (10 mg/kg for 7 days),
low and high doses of S. anacardium (100 and 500 mg/kg for 21
days) and their combination
orally and subsequently subjected to isoproterenol
administration (150 mg/kg, sc) for two
consecutive days. The influence of prophylactic treatment was
analysed by quantification of
biomarkers and antioxidants, electrocardiographic parameters and
histopathological
observations. The activities of lactate dehydrogenase and
creatinine phosphokinase-MB were
reduced in serum and raised in heart tissue with concurrent
elevation in superoxide dismutase
and catalase activities as well as reduction in thiobarbituric
acid reactive species levels
significantly in all treated groups compared to isoproterenol
group. Similarly,
electrocardiographic changes were restored to normalcy in all
treated groups. To conclude,
combination of high dose of S. anacardium with propranolol was
found to be most effective in
alleviating the abnormal conditions induced by
isoproterenol.
This study was to elucidate the role of S. anacardium nut
extract during
myocardial dysfunction and metabolic derangement induced by
isoproterenol in rat heart and
also to explore its pharmacodynamics interaction with
conventional cardio protective drug.
Propranolol. The results revealed the beneficial role of S.
anacardium when treated
concurrently with propranolol in conditions of anticipated
cardiac injury.
Results it may be concluded that the SANE both at low (100
mg/kg) and high doses (500
mg/kg) possess cardio protective efficacy when given
prophylactically in experimental
animals. Moreover, combined therapy of SANE and PRO demonstrated
synergistic cardio
protective potential than when they were used alone. The
combination of high dose of SANE
and PRO was found to have best effect. However, combined therapy
of SANE and PRO must
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Exploring therapeutic Potential of Bhallataka for
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be further refined for adjustment of doses as higher doses of
SANE and PRO may pose
negative implication due to excessive pharmacological
effects.
2.5 Adverse effects of bhallataka:
Impure or pure bhallataka if taken in excess dose, cause
pruritus and burning sensation of anus
and tip of the penis, excessive perspiration, thirst and reduced
red dusky urination, in such
condition, one should or stop taking bhallataka and should start
pitta alleviating drug like
doorvadigana, sarivadigana. In condition like burning sensation
or pruritus and swelling of
skin, sesamum oil, coconut oil, resin ointment should be applied
locally: In 3-4 ghee or days
the above symptoms subside. The above should be kept handy
before starting Bhallatak
treatment.34
2.6 Safety profile:
The drug should be used with care, preferably under the
direction of a qualified practioner,
since the Anacardic acid are allergenic. The maximum tolerated
dose of a 50% alcoholic extract
of the fruit when given interaperitoneally to mice was found to
be 250/mg/kg body weight.35
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3. Phytochemical profile of Semecarpus Anacardium.
SA 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
phyto pharmaceuticals 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 In
alternative medicine, medicinal plant preparations have found
wide spread 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.36 Various anacardoflavanone have been isolated
from the nut shells and
characterized isolated one more biflavonoid namely
tetrahydrorobustaflavone from the
defatted nuts of the S. anacardium and structure characterized.
The leaves of the S. anacardium
found to contain amentoflavone as the sole compound. 37The
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. 38 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- -D-glucopyranosyl- (1 - 6) -
-D-glucopyranosyloxy-3- hydroxy-5-
methylbenzene.39
Table 2: Qualitative Phytochemical Analysis of Various Extracts
of Semecarpus
anacardium Leaves.
S. No.
Name of the Test
Procedure
Observation Soxhlet Extracts of Leaves
1. Alkaloids A B C D E F G H I J K L M N
i Dragendo
rffs Test Orange Red
ppt.
- - - + - - - - - - - + - -
ii Mayers Test
Whitish
Yellow or
Cream
coloured
ppt.
- - - + + - - + - - - - + -
iii Hagers Test
Yellow
coloured
ppt.
- - - - - - - + - - - + + -
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iv Wagners Test
Reddish
Brown ppt.
- - + + - + + + - - + + + +
2. Saponins A B C D E F G H I J K L M N
i Foam
Test
Foam
persists for
10mins.
+ - - + + - - - + - - - + -
3. Carbohydrates A B C D E F G H I J K L M N
i Molisch
Test
Purple or
reddish
violet color.
- - - - - - - - - - - + - -
ii Fehlings Test
Brick Red
ppt.
- - - - - - - - - - - - + -
iii Benedicts Test
Red ppt. - - - - - - - - - - - - + -
4. Glycosides A B C D E F G H I J K L M N
i Legals Test
Pink to Red
color.
+ - + + + + - - - - + - + -
ii Baljet
Test
Yellow to
Orange
color.
+ + - + - - + + + + - + - -
5. Tannins A B C D E F G H I J K L M N
i Lead
acetate
Test
White ppt. - - - - - - - - - - - - - -
ii Ferric
chloride
Test
Dark Blue
or Greenish
Black.
- - - - - - - + - - - - - -
iii Potassium
dichromat
e Test
Yellow
color ppt.
- + + - - - + + + + - - - -
iv Gelatin
Test
White ppt. - - + + + - - + + + - + + -
v Potassium
ferric
cyanide
Test
Deep red
color.
- - - - - - - - - - - - - -
6. Flavonoids A B C D E F G H I J K L M N
i Shinodas Test
Cherry Red
color.
- - - - + - - + - - - + - -
ii Alkaline
Reagent
NaOH
Test
Intense
Yellow
color.
- + - + + - + + - + - + + +
iii H2SO
4
Test
Yellow or
Orange
color.
- + + + + - + + + + + + - -
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Exploring therapeutic Potential of Bhallataka for
Immunomodulatory activity | 16
iv Lead
acetate
Test
Yellow
color ppt.
+ + - + - - - + + - - + + +
7. Steroids A B C D E F G H I J K L M N
i Salkowsk
i Test
Bluish red
to cherry
color in
Chloroform
layer &
Green in
acid layer.
- + - - - - - + - - + + - +
ii Liberman
n
burchard
Test
Brown ring
at junction
& green or
deep red
upper layer.
- + - + - - + - + + + + - +
8. Phenols A B C D E F G H I J K L M N
i Ferric
chloride
Test
Bluish
Black color.
- - - - - - - + - - - - - -
9. Proteins A B C D E F G H I J K L M N
i Biuret
Test
Pinkish or
Purple
violet color.
- - - - - - - - - - - - - -
ii Ninhydrin
Test
Blue color. - - - - - - - - - - - - - -
iii Xanthopr
oteic Test
Orange
color.
- - + + - - - + - + - + + -
10. Monosaccharide A B C D E F G H I J K L M N
i Barfoeds Test
Red ppt. - - - - - - + - - - - - - -
11. Hexose Sugars A B C D E F G H I J K L M N
i Selwinoff
s Test for ketohexos
e like
fructose
Red color. + - - + - - - + + + - + - -
ii Tollens phloroglu
cinol Test
for
galactose
Yellow to
Red color.
+ + + + + + + + + + + + + -
iii Cobalt
chloride
Test
Upper layer
Greenish
blue &
+ + + + + + + + + + + + + +
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Exploring therapeutic Potential of Bhallataka for
Immunomodulatory activity | 17
Lower
Purplish.
12. Diterpenes A B C D E F G H I J K L M N
i Copper
acetate
Test
Emerald
Green
color.
+ + - - + - + + + + + + - +
13. Nonreducing
Polsaccharides [Starch]
A B C D E F G H I J K L M N
i Iodine
Test
Blue color. - - - - - - - + - - - - - -
ii Tannic
acid Test
ppt
formation.
- - - - + - - + - - - - - -
14. Mucilages & Gums A B C D E F G H I J K L M N
i Rutheniu
m Red
Test
Pink color. + + - - - - + + + + - - - -
(+ ) = indicates presence, ( - ) = indicates absence.
A= water, B= chloroform, C= toluene, D= carbon tetrachloride, E=
ethyl acetate, F= hexane,
G= ethyl alcohol, H= methanol, I= acetone, J= 2-propanol, K=
petroleum ether 60-80 C, L=
2-butanone, M= dichloromethane, N= ethyl ether.40
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Exploring therapeutic Potential of Bhallataka for
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4. Shodhana of SA (Purification)
Bhallataka (SA) is reported under upavisha dravya (semi
poisonous drugs), in classical
Ayurvedic pharmacopoeias. It is advocated that shodhana
(Purificatory procedures) of the
fruits should be carried out before its internal administration.
Though there are different
shodhana methods mentioned in Ayurveda, Ayurvedic Pharmacopoeia
of India (API)
recommends only one method for the shodhana of Bhallataka
fruits. In study, cows urine,
cows milk and brick powder, were used as media. Ayurveda
advocates bhallataka after
shodhana (purificatory procedures).Though there are different
shodhana methods mentioned
in Ayurveda41
4.1 Effects of Non-Purified (SA) and effect of liquid media in
shodhana
In Ayurvedic literature, the synonym Sopha hetu, Spota hetu,
agnika are given to this drug
based on its blister causing nature. The oil in the fruit is
responsible for the irritation. The
bhallataka fruit contains 90% Anacardic acid and 10% of Cardol.
Other chemical constituents
are bhilawanol , semecarpol and anacardol. Recent studies
reported that bhilawanols are known
as urushiols. Anacardic acids are closely related to urushiol.
Another study reported that the
corrosive juice from the pericarp of the fruit is 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. The media
gomutra (cows urine) is
reported for its antimicrobial, antibacterial etc. Cows milk is
recommended as one of the
antidote for bhallataka blisters. Brick powder is having
adsorbent property; by which it absorbs
irritant oil in the fruit.42
4.3 Method of Sodhana
Bhallataka fruits, sunken in water, were randomly taken. The
thalamus portion of the fruits
was removed with the help of a steel cutter. Then it was taken
in a vessel containing gomutra
(cows urine) and kept for seven days. Every day the fruits were
taken out of the media and
washed with water and fresh gomutra was used. On eighth day
Bhallataka was washed and
shifted to the vessel containing godugdha (cows milk) and kept
for seven days. Each day it
was washed with water and fresh Godugha was added. On 15th day
the samples were taken
out of the media and washed with water then shifted to a bag
containing brick powder and
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Exploring therapeutic Potential of Bhallataka for
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rubbed thoroughly. It was allowed for three days in the bag
containing brick powder. On 18th
day it was washed thoroughly with hot water to remove the brick
powder in the sample. Later,
the samples were dried properly to remove the moisture and
stored in air tight glass container
for further studies. The same shodhana procedure was repeated
thrice to standardize the
procedure pharmaceutically.
4.4 Impact on Anacardol Content.
Due to the decorboxylation of the oil, the anacardic acid gets
converted into less toxic
anacardol. Decorboxylation process may start right from cutting
the fruit itself and will be
catalysed by giving heat/fire Treatment.43 The increased level
of anacardol in the shodhita
bhallataka may be due to the decorboxylation of the anacardic
acid in the fruits. More
percentage of oil might have got reduced by soaking the fruits
in the gomutra and godugda.
The brick powder is having the adsorbing nature, so some
percentage of oil may be absorbed
by the brick powder. There are probable chances that some
chemical changes might have taken
place due to the various Medias like gomutra, godugda etc used
for its purification. Further
studies should be carried out to find out the chemical
interactions between the media and the
bhallataka fruits during shodhana procedure. Anacardol in raw
bhallataka was 47.51% and
50.62% in processed. Shodhana (purificatory procedure) increases
the anacardol level in
shodhita bhallataka fruit samples. More percentage of the
anacardol was due to the conversion
of toxic urushiol into Anacardol.44
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Exploring therapeutic Potential of Bhallataka for
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5. Methods for Testing (SA) Immunological Factors
The whole animal model is the most classic pharmacological
screening model, which is very
important at the aspect of medicine evaluation because it can
apparently respond to the efficacy,
side effect and toxicity of medicines in whole. Although this
method is high cost and low
efficient, at present it is still a primary way to drug
discovery and evaluation. Several in vitro,
in vivo methods of pharmacological screening of medicinal plants
having immunomodulatory
activity have been listed.45
5.1 In vitro methods:
1. Inhibition of histamine release from mast cells
2. Mitogens induced lymphocyte proliferation
3. Inhibition of T cell proliferation
4. Chemiluminescence in macrophages
5. PFC (plaque forming colony) test in vitro
6. Inhibition of dihydro-orotate dehydrogenase
5.2 In vivo methods:
1. Spontaneous autoimmune diseases in animals
2. Acute systemic anaphylaxis in rats
3. Anti-anaphylactic activity (Schultz-Dale reaction)
4. Passive cutaneous anaphylaxis
5. Arthus type immediate hypersensitivity
6. Delayed type hypersensitivity
7. Reversed passive arthus reaction
8. Adjuvant arthritis in rats
9. Collagen type II induced arthritis in rats
10. Proteoglycan-induced progressive polyarthritis in mice
11. Experimental autoimmune thyroiditis
12. Coxsackievirus B3-induced myocarditis
13. Porcine cardiac myosin-induced autoimmune myocarditis in
rats
14. Experimental allergic encephalomyelitis
15. Acute graft versus host disease (GVHD) in rats
16. Influence on SLE-like disorder in MRL/lpr mice
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Exploring therapeutic Potential of Bhallataka for
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6. Experimental Protocol to evaluate (SA) immunomodulatory
activity.
Determination of the immunomodulators effects of SA extracts in
adjuvant induced arthritic
(AIA) rat model. AIA is an erosive autoimmune polyarthritis
involving both humoral and cell
mediated immune responses that resemble human rheumatoid
arthritis (RA). At cellular level
immunosuppression occurred during the early phase of the
disease. There was mild synovial
hyperplasia and infiltration of few mononuclear cells in SA
treated animals. The induction of
nitric oxide synthase (NOS) was significantly decreased in
treated animals as compared to
controls. These observations suggest that the herbal extracts
caused immunosuppression in
AIA rats, indicating that they may provide an alternative
approach to the treatment of arthritis.
6.1 Adjuvant arthritis in Animal (Rats).
6.1.1 Animal Model.
Both male and female albino rats (Sprauge Dawley Strain) 10 rats
taken 5 male 5
female.
6.1.2 Development of arthritis.
Rats were injected with 300 l of Complete Freunds Adjuvant (CFA)
in the right hind footpad
and left overnight for development of inammation.
6.1.3 Evaluation of arthritis.
Measuring the thickness of inamed ossicular tissue using a dial
gauge calliper assessed degree
of arthritis. Severity of inammation was classied using a
six-point scale based on
enlargement, erythema and edema of the tissue.
6.1.4. Treatment
To determine the optimum dose, animals were initially treated
with 200, 100, 50, 25, 12.5, and
200 mg/kg body weight of the SA Extract separately.
Intraperitoneal administration the
according to body weight it should be found to be the optimum
dose for immunomodulatory
property, hence used for further studies. All the animals
received SA for 25 days.
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Exploring therapeutic Potential of Bhallataka for
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6.2. Lymphocyte proliferation assay used to determine the Cell
mediated immunity.
Lymphocyte proliferation assay can be performed using mitogen
Con-A. Both the treated and
untreated animals were sacriced to remove the spleen in
RPMI-1640 medium. Spleen was
crushed and cell suspension was washed with plain medium. Cells
were lysed with 0.9%
ammonium chloride and re suspended in complete medium with 10%
fetal calf serum. Cells
were cultured at a nal concentration of 3 105cells/100 l/well in
triplicate in at bottom
microtiter tissue culture plates. The optimal concentration of
0.05 g/ml (in vitro concentration
titration done earlier) of both the extracts was added to the
wells separately and in combination
with Con-A (5.0 g/ml). After 3 days of incubation at 37 C under
humidied air supplemented
with 5% CO2 , 1 ci Hthymidine was added to each well. Six to
eight hours later cells were
harvested and aspirated on to glass-ber lter papers using NUNC,
Automatic Cell Harvester
and the radiolabel incorporated into DNA was counted using LKB
auto beta counter.
6.3. Histology of joint tissues.
Rats were sacriced to remove the knee joints. Specimens were xed
for 24 h in 2%
glutaraldehyde in phosphate buffer saline, bisected, decalcied
and returned to 2%
glutaraldehyde and submitted for routine parafn embedding.
Tissue sections were stained
using hematoxylin and eosin stain. The histological ndings were
graded on the basis of
synovial hyperplasia and mononuclear cell inltration.
6.4. Measurement of induction of NO in activated macrophages (
Estimation of Nitric
oxide production )
Macrophage activation assay was performed by injecting rats with
thioglycolate
intraperitoneally 72 h prior to sacrice. On the day of sacrice,
cold RPMI-1640 incomplete
medium was administered intraperitoneally to ush out the
activated macrophages. The process
was repeated 810 times to obtain a good yield of macrophages.
Once the activated
macrophages were recovered, cells were centrifuged and washed
thrice with plain medium,
counted and plated at a nal concentration of 5 105cells/well.
Plates were incubated for 4h
at37C in CO2 incubator. Floating cells were removed and the
wells were washed twice with
warm medium to avoid the leaching of the adhered macrophages.
Cells were then treated with
0.05 g/ml of SA. Culture soup was collected for estimation of NO
production by Griess
Reagent method. Briey, 100 l of cell supernatant mixed with 1%
sulfanilamide/0.1%
naphthylethylenediamine/2.5% H3PO was incubated at room
temperature for 10 min to form
a chromophore. The absorbance was read at 550 nm and NO was
measured using NaNO2as
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Exploring therapeutic Potential of Bhallataka for
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standard. Quantitation was done against standard curve generated
using known quantities of
sodium nitrite.46
6.5. Cell culture
Mononuclear cells were isolated from heparinized venous blood
and synovial uid (SF) by
density sedimentation method). Briey, blood/SF was diluted in
phosphate buffered saline
(PBS), pH 7.2 and layered carefully on lymphoprep at a ratio of
3:1 and centrifuged at 1800
rpm for 30 min. Cells in the interface layer were carefully
separated, washed with PBS thrice
and resuspended in RPMI 1640 supplemented with 25 mM HEPES, 2 mM
L-glutamine,
penicillin (100 U/ml), streptomycin (100 _g/ml) and 10%heat
inactivated Fetal Bovine Serum
(FBS). Cell concentration was adjusted as per the requirement of
the experiment. Cell viability
after 18 h was assessed by mitochondria-dependent reduction of a
yellow tetrazolium dye 3-
[4,5-dimethylthiazol-2yl]-2, 5-diphenyltetrazolium bromide to
insoluble purple formazan by
dehydrogenases at the end of 18 h culture. It will showed the
Percentage cell viability.
6.6. Cytokine ELISA
Cells were treated with LPS (10 ng/ml) in presence and absence
of different doses (1.0, 0.5 and
0.2 mg/ml) of Semecarpus anacardium crude ethanolic extract. The
culture was incubated for
18 h at 37 C, 5% CO and supernatants and cells were harvested
for ELISA and RNA extraction,
respectively. Pro inammatory cytokines TNF-alpa, IL-1beta, IL-6
and IL12p40 in the culture
supernatants were estimated by commercial sandwich ELISA
according to the manufacturers
instruction. Briey, plates were coated with monoclonal capture
antibody by overnight
incubation at 42C and blocked with 10% FBS in phosphate buffered
saline (PBS) for 1 h.
Samples and recombinant standards were added to the plates and
incubated for 2 h. Cytokines
were detected by addition of horseradish peroxidase conjugated
streptavidin labelled
antibodies. Color was developed using tetramethylbenzidine (TMB)
for 15 min and absorbance
was recorded at 450 nm.47
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Exploring therapeutic Potential of Bhallataka for
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7. Reported immunomodulatory activity of Semecarpus
anacardium.
Table 4. Reported Immunomodulatory activities of Semecarpus
anacardium
S.No Extract :
E/
Formulati
on : F
Description In vivo models
or
In vitro models
Reported
mechanism of
action/Level
Dose Ref
No.
1 Nut milk
extract : E
Nut Milk Extract in
Aflatoxin B1 -induced
Hepatocellular
Carcinoma in
Rats.Immunomodulat
ory activity was
assessed by measuring
serum
immunoglobulin (Ig)
levels in control and
experimental animals.
Reduced IgG and
elevated IgA and IgM
in the
hepatocellular
carcinoma condition
were returned to near
normal levels in rats
treated
Adult Male
albino wistar
rats
Returned to
near normal
levels of
Reduced IgG
and elevated
IgA and IgM
200
mg/kg
48
2 Nut
ethanolic
extract
(endotoxin
free):E
Immunomodulatory
activity of the nut
extracts at 1g/mL in
mononuclear cells of
production normal.
Humans
cells(Vitro)
-Cell culture
-Cytokine ELISA
-Nitric oxide
(NO) estimation
-RT-PCR
-Electrophoretic
Mobility Shift
Assay (EMSA)
Inhibition of
proinflammato
ry cytokine
production
1g/m
L
49
3 Nut milk
extract : E
The components of
immune system levels
of reactive oxygen
species (ROS), namely
Hydroxy radical,
Superoxide radical,
and H2O2 were also
measured in spleen,
thymus,
and lymphocytes
Adult Male
albino wistar
rats
A significant
increase in the
level of LPO,
ROS
150
mg/kg
50
4 Kalpaamr
uthaa :F
Kalpaamruthaa (KA)
is a modified Siddha
Female albino
SpragueImmunoglobul
ins, and
200
mg/kg
51
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Exploring therapeutic Potential of Bhallataka for
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7.1. Balchandran Premalatha et al (1998) has reported
Immunomodulatory Activity of
Semecarpus anacardium Linn. Nut Milk Extract in Aflatoxin B
-induced Hepatocellular.
Administration of 200 mg kg- S. anacardium nut milk extract
brought immunoglobulin levels
back to near normal levels in HCC-induced rats.This indi cates
the immunomodulatory effect
of the nut milk extract in a growing tumour, and it wouldbe
effective in inhibiting the growth
of an established tumour.No significant change in
immuno-globulin levels in drug control
animals suggests that the drug did not produce any immunotoxic
effects. The combined
antitumour potency and immuno-modulatory activity of S.
anacardium nut milk extract make
it potentially useful in the treatment orprevention of
immune-based diseases such as cancers.
7.2. Singh, Divya, et al.(2006) Reported Immunomodulatory
activity of Semecarpus
anacardium extract in mononuclear cells of normal individuals
and rheumatoid arthritis
patients
The suppressive activity of SA extract demonstrable in normal
mononuclear cells was also seen
where peripheral blood and synovial mononuclear cells of RA
patients were used. Rheumatoid
arthritis is marked by chronic synovitis and abundance of
proinammatory cytokines, TNF-
alpha IL-1beta, IL-6 and IL-12p40, produced primarily by
stimulated monocytes, macrophages
and synovial lining cells
preparation, which has
been formulated. It
contains Semecarpus
anacardium Linn.
(SA), Emblica
officinalis (EO), and
honey. Synergetic
Immunomodulatory
activity
Immunomodulatory
effect of
Kalpaamruthaa on
7,12-dimethyl
benz(a)anthracene-
induced mammary
carcinoma studied in
rats
Dawley rats of
Wistar stain
glycoprotein
components to
near normal
levels
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Exploring therapeutic Potential of Bhallataka for
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The suppression of IL-1_ and IL-12p40 along with NF-_B and AP-1,
therefore, suggests that
SA may have important constituents that will have benets for
this disease.We have also shown
the SA suppressed LPS activated nitric oxide production by the
extract in mouse macrophage-
like cell,RAW264.7. This is not surprising since nitric oxide
production is regulated by iNOS
gene that has promoter regions for NF-KB.NO also plays a role in
the pathogenesis of RA and
therefore, its suppression by SA extract adds an additional
advantage for its anti-disease
activity
7.3. Ramprasath, et al.(2006) Reported "Evaluation of
antioxidant effect of Semecarpus
anacardium Linn. nut extract on the components of immune system
in adjuvant arthritis.
Semecarpus anacardium Linn. Nut extract was investigated by
studying the extent of lipid
peroxidation and the activities of SAD, CAT, GPx, GSH, and ROS
in the lymphocytes and
lymphoid organs (spleen, thymus) in control and experimental
rats. Anti-arthriticeffect was
studied from the changes in the paw thickness as a measure of
paw edema and arthritic score
in arthritic and drug treated rats. In arthritic rats the extent
of LPO and ROS were elevated
profoundly and the antioxidants (SOD, CAT, GPx, GSH) were found
to be significantly
decreased. CRP levels and ESR were also found to be
significantly increased in arthritic rats.
These changes were brought back to near normal levels on
treatment with the drug. No
significant changes were observed in drug alone treated control
rats. The paw thickness and
arthritic scores were very much increased in arthritic rats,
which was significantly reduced on
treatment with the drug. These effects can be attributed to the
presence of flavonoids and other
synergistic components in the drug.
7.4. Dharmendra et al.(2014) Immunomodulatory effect of
Kalpaamruthaa on 7, 12-
dimethyl benz (a) anthracene-induced mammary carcinoma studied
in rats."
Kalpaamruthaa (KA) is a modified Siddha preparation, which has
been formulated in our
laboratory. It contains Semecarpus anacardium Linn. (SA),
Emblica officinalis (EO), and
honey in a definite ratio. The component study of this herbal
preparation revealed the presence
of flavonoids, ascorbic acid, polyphenols, tannins, sugars,
sterols, etc. Dose-dependent study
of Kalpaamruthaa was carried out in mammary carcinoma-bearing
rats, which helped us fix
300 mg/kg body weight as the effective
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Exploring therapeutic Potential of Bhallataka for
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This reduction in the levels of glycoprotein components
indicates that the drug KA has
the ability to suppress malignancy by modulating the cell
transformation, decreasing the degree
of metastasis, inhibiting the progression of growth, and
controlling the cancer cell proliferation
and differentiation by causing effective favorable changes in
the structure of cell membranes.
This could be due to the cytostabilizing property of the drug
and also due to inhibitory action
of flavonoids against carcinogenesis
In this study suggest that DMBA-induced mammary carcinoma is
associated with
immune suppression and the drug KA by means of its
immunomodulating effect can serve as
a better anticancer agent. The results also suggest that KA is
found to be more effective than
SA, which may be due to the amalgamated and additive effects of
SA, E.officinalis, and honey
present in the drug.
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Exploring therapeutic Potential of Bhallataka for
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8. Toxicological studies of Semecarpus anacardium.
8.1.1.Patwarddhan et al ., 1988 have reported the toxicity of
Semecarpus anacardium.
extract
Toxicity by oral route administration of SA with peanut oil was
compared against the same
extract emulsified with Tween-80 saline. The traditional way of
administration with peanut oil
was found to be safe and upto 25 mg/kg/day x9 days, increase in
weight, RBCs & haemoglobin
% was observed without mortality. Same dose with Tween-80 saline
was found to have adverse
effects regarding all the parameters with 16.5% mortality. This
study support Ayurvedic
method of administration for efficacy without toxicity.
The toxicity of bibba can be controlled by administration with
peanut oil or similar
vehicles. Upto 25 mg/kg/day dose bibba can be given safely for
therapeutic uses. It can act as
a good hematinic agent and as a general tonic. Ayurvedic method
of administration has shown
reduction in toxicity with maintained efficacy.
8.1.2. Vijayalakshmi et al.,2000 have been reported Toxic
studies on biochemical
parameters carried out in rats with Serankottai nei, a siddha
drug-milk extract of
Semecarpus anacardium nut.
A toxicological study was carried out in rats with a Siddha
preparation, milk extracts
of SA. The effect of acute (72 h) and subacute (30 days)
treatment of the drug with different
dosage on liver and kidney functions and haematological
parameters were studied. The acute
toxicity studies with this drug did not produce mortality at any
dose level given (75-2000 mg/kg
body weight). No marked adverse alterations were observed in
haematological and biochemical
parameters during the subacute toxicity studies (50, 100, 250
and 500 mg/kg body weight). In
the subacute treatment, the highest dose (500 mg/kg body weight)
alone showed a moderate
increase in the level of blood glucose, plasma urea, uric acid,
and creatinine. In addition,
alteration in lipid profiles were observed which may be
attributed to the ghee preparation of
the drug. Decrease in urinary urea, uric acid and creatinine
levels were also observed. Histo-
pathological examination of vital organs showed normal
architecture suggesting no
morphological disturbances.The present study shows that the
Siddha preparations of S.
anacardium nuts do not induce any toxic manipulation on the
biochemical parameters
investigated. From these one can infer and hypothesize that this
drug is nontoxic and can be
used as therapeutic agent in treating the reported diseases
effectively.
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Exploring therapeutic Potential of Bhallataka for
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9. Conclusion
SA reported to be a potent immunomodulator. Scientific studies
have proven the efficacious role
in preventive medicine and in the management of chronic
degenerative diseases. It would
provide an alternative to conventional chemotherapy for a
variety of immunological disorder.
Majorly the evaluation of SA as immunomodulators done by using
various models and
techniques such as; Adjuvant arthritis in rats (AIA), Lymphocyte
proliferation assay,
Measurement of induction of NO in activated macrophages, Cell
culture, Cytokine ELISA.
Recent studies found out that the SANE can inhibit proinammatory
cytokine production. The
nut milk extract is effective in restoring the fragility of
lysosomal membranes in aflatoxin-
induced hepatocellular carcinoma. The crude extract also
suppressed LPS induced nuclear
translocation. The extract also suppressed LPS activated nitric
oxide production in mouse
macrophage cell line. And the maximum tolerated dose 250 mg/kg
body weight in 50%
alcoholic extract of the fruit when given interaperitoneally to
mice was found to be safe.
Ayurvedic method of administration has shown reduction in
toxicity with maintained efficacy.
It also shows a drug interaction with propranolol against
isoproterenol induced myocardial
damage in rats.
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Exploring therapeutic Potential of Bhallataka for
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10. Future strategies.
Besides mention in classic Ayurveda texts and claims of
traditional physicians, it is noted that
evidence through scientific studies is emerging to demonstrate
the benefits of SA
immunomodulation. However, the definite lacuna in all research
publications reviewed in this
report is the inadequate probing into Ayurvedic science. This
has led to superficial correlations,
where the plant drugs have remained as mere candidates for
testing against selected
pharmacological reactions. Deciphering deeper into Ayurvedic
concept behind
Immunomodulation can help identify better candidates and models
for study.
And it will help for selection of clinical and experimental
studies. The later are not adequate at
present, but it is worthwhile to project such evidences to
provide lead for further studies. Drug
discovery strategies based on natural products and traditional
medicines are remerging as
attractive options. A reverse pharmacology approach, inspired by
traditional medicine and
Ayurveda, can offer a smart strategy for new drug candidates to
facilitate discovery process
and also for the development of rational synergistic botanical
formulations.
With respect to the possible future clinical potential of
immunomodulation activity is the
observation that therapeutic dosing with SA inhibited
established arthritis in rats. The plant-
derived immunomodulators thus have tremendous future potential
for developing new
pharmaceutical products. Phytochemical analysis of these SANEs
is in progress to identify
bioactive molecules responsible for immunomodulatory properties
in these plants.
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Exploring therapeutic Potential of Bhallataka for
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11. References
1 "The World Health Report " (2013) WHO Page no - 9
2 Govindarajan R, Vijayakumar M, Pushpangadan P (2005).
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