The modulating effect of Garcinia Cambogia extract on - medIND

Indian Journal <strong>of</strong> Pharmacology 2001; 33: 87-91 SHORT COMMUNICATION
Correspondence: C.S. Shyamala Devi
GARCINIA CAMBOGIA AND ETHANOL INDUCED PEROXIDATION
THE MODULATING EFFECT OF GARCINIA CAMBOGIA EXTRACT ON ETHANOL
INDUCED PEROXIDATIVE DAMAGE IN RATS
SUMMARY
KEY WORDS
P. MAHENDRAN, C.S. SHYAMALA DEVI
Department <strong>of</strong> Biochemistry & Molecular Biology, University <strong>of</strong> Madras, Guindy Campus,
Chennai - 600 025.
Manuscript Received: 25.5.2000 Revised: 14.6.2000 Accepted: 13.7.2000
Objective: To determine the <strong>modulating</strong> <strong>effect</strong> <strong>of</strong> <strong>Garcinia</strong> cambogia fruit <strong>extract</strong> on ethanol induced
peroxidative damage in rats.
Method: Male albino rats weighing 125 to 150g were administered ethanol (7.11g per kg body weight /
day) for 45 days. Ethanol administered rats were treated concomitantly with <strong>Garcinia</strong> cambogia fruit
<strong>extract</strong> (1g/kg body weight / day) orally for 45 days. After the experimental period the antioxidant enzymes,
LPO, conjugated diene in the liver tissue, serum AST, ALT and alkaline phosphatase and lipid levels in
both serum and liver tissue were estimated.
Results: Co-treatment <strong>of</strong> the rats with <strong>Garcinia</strong> cambogia significantly inhibited the rise in lipid levels
and also the peroxidative damage caused by ethanol, which is evident from the improved antioxidant
status. <strong>The</strong> levels <strong>of</strong> serum AST, ALT and alkaline phosphatase were maintained at near normalcy in
<strong>Garcinia</strong> cambogia treated rats.
Conclusion: <strong>The</strong> imbalance in lipid metabolism could be the reason for increase in lipid peroxidation. In
our present study the treatment with <strong>Garcinia</strong> cambogia fruit <strong>extract</strong> resulted in reduction <strong>of</strong> both serum
and liver lipid to near normalcy. This hypolipidemic property <strong>of</strong> <strong>Garcinia</strong> cambogia in turn reduces the
peroxidative damage, enhanced by ethanol.
Ethanol <strong>Garcinia</strong> cambogia lipid peroxidation hyperlipidemia antioxidant enzymes
INTRODUCTION
Liver being the major site for detoxification is the primary
target for environmental or occupational toxic
exposure 1 . <strong>The</strong> alcoholic liver injury appears to be
generated by the <strong>effect</strong>s <strong>of</strong> ethanol metabolism and
the toxic <strong>effect</strong>s <strong>of</strong> acetaldehyde which may be mediated
by acetaldehyde altered proteins 2 . Chronic
alcohol intake is known to produce hypercholesterolemia,
hyperlipidemia, hypertriglyceridemia 3,4 . In
chronic lipid accumulation the liver cells become fibrotic
and leads to impaired liver function. Enhanced
lipid peroxidation has been reported in hyperlipidemia
5 , which is also induced by ethanol 3,4 . Ethanol
increases triglycerides and cholesterol levels thus
inducing imbalance in lipid metabolism in liver, heart,
kidney and other organs and this could explain the
reason for the increase in lipid peroxidation in these
organs. Recently free radical induced lipid peroxidation
has gained much importance because <strong>of</strong> its in-
volvement in several pathologies 6,7 . Protection <strong>of</strong> cell
membrane from lipid peroxidation becomes a necessity
to prevent, cure or delay the aforesaid patho-logies.
Rind <strong>of</strong> the fruits <strong>of</strong> <strong>Garcinia</strong> cambogia (Gaertn.)
Desr. (Clusiaceae) is an astringent and is useful in
the treatment <strong>of</strong> ulcers, haemorrhoids, diarrhoea and
dysentry 8,9 . <strong>Garcinia</strong> cambogia fruit <strong>extract</strong>, containing
the principle organic acid, (-)-erythro-L s -
hydroxycitric acid is a powerful anti-lipogenic agent 10 .
<strong>The</strong> present study is an attempt to elucidate the
antiperoxidative property <strong>of</strong> <strong>Garcinia</strong> cambogia on
ethanol induced peroxidative damage and its efficacy
to inhibit lipid peroxidation.
MATERIALS AND METHODS
Animals: Male albino rats weighing 125 to 150 g
were purchased from FIPPAT, Padappai, Chennai.
<strong>The</strong> animals were housed in plastic bottom cages

88
P. MAHENDRAN AND C.S. SHYAMALA DEVI
Table 1. Serum and hepatic levels <strong>of</strong> total cholesterol, triglycerides, free fatty acids, phospholipids, alkaline phosphatase, aspartate
amino transferase (AST), alanine amino transferase (ALT) in experimental groups a .
I II III IV ANOVA
Parameters b Control Group 18% Ethanol treated <strong>Garcinia</strong> cambogia <strong>Garcinia</strong> cambogia F value*
(n = 6) group (n = 6) treated group + 18% ethanol treated
(n = 6) group (n = 6)
Total cholesterol A 70.4 ± 1.18 113.2 ± 2.19*** 64.3 ± 1.26*** 72.2 ± 1.81*** 4.24
B 4.36 ± 0.37 6.82 ± 0. 51*** 3.72 ± 0.51* 4.76 ± 0.40*** 2.88
Triglycerides A 107.8 ± 2.08 156.0 ± 2.14*** 98.5 ± 2.09*** 112.9 ± 2.11*** 3.97
B 4.23 ± 0.41 5.87 ± 0.50*** 3.73 ± 0.46* 4.54 ± 0.40*** 2.94
FFA A 64.1 ± 1.96 115.4 ± 2.28*** 56.6 ± 1.64*** 70.8 ± 2.07*** 3.68
B 11.5 ± 0.93 21.6 ± 1.67*** 9.9 ± 0.81** 13.2 ± 1.24*** 3.24
Phospholipids A 115.6 ± 2.06 142.4 ± 2.17*** 110.3 ± 1.98** 126.7 ± 2.23*** 3.07
B 23.1 ± 2.15 38.7 ± 1.83*** 20.6 ± 1.91* 30.4 ± 1.47*** 2.90
Alkaline Phosphatase A 0.76 ± 0.05 1.57 ± 0.04*** 0.69 ± 0.04 NS 0.86 ± 0.03*** 2.78
B 1.41 ± 0.04 0.88 ± 0.03*** 1.34 ± 0.05 NS 1.19 ± 0.04*** 2.91
AST A 0.48 ± 0.04 0.83 ± 0.03*** 0.41 ± 0.04 NS 0.52 ± 0.04*** 2.83
B 0.72 ± 0.06 0.46 ± 0.04*** 0.78 ± 0.05 NS 0.69 ± 0.05*** 2.79
ALT A 0.63 ± 0.04 0.92 ± 0.04*** 0.61 ± 0.04 NS 0.58 ± 0.03*** 2.96
B 1.04 ± 0.03 0.68 ± 0.02*** 1.07 ± 0.03 NS 0.93 ± 0.03*** 2.81
A : Serum B : Liver. a Values are expressed as mean ± SD for 6 animals in each group.
Students ‘ t ’ test: Group II vs Group I, Group III vs Group I, Group IV vs Group II. *p < 0.05; **p < 0.01; ***p < 0.001
b <strong>The</strong> values <strong>of</strong> lipids in serum are expressed as mg/dl. <strong>The</strong> values <strong>of</strong> AST, ALT and ALP in serum are expressed as µkat/litre.
<strong>The</strong> levels <strong>of</strong> AST and ALT in liver are expressed as µ moles <strong>of</strong> pyruvate liberated/sec/g protein. <strong>The</strong> level <strong>of</strong> ALP in liver is expressed
as µ moles <strong>of</strong> phenol liberated/sec/g protein.
F - test, * Significant at level <strong>of</strong> 5% (2.77).
and allowed free access to standard laboratory chow
(Hindustan Lever Foods, Bangalore, India) and water.
Drug: <strong>Garcinia</strong> cambogia fruit <strong>extract</strong> was obtained
from Siris Herbex, Vijayawada, India. Absolute alcohol
(99%) was purchased from Anilax Chemicals,
USA. All other chemicals used for the experiment
were <strong>of</strong> analytical grade.
Grouping
Group I - Normal Control (n = 6).
Group II - Rats given 18% ethanol (7.11g/kg body
weight day) 5 ml/100 g body weight for
45 days (n = 6).
Group III - Normal rats given <strong>Garcinia</strong> cambogia
1 g/kg body weight/day orally for 45 days
(n = 6).
Group IV - Rats given 18% ethanol (7.11g/kg/body
weight/day) + <strong>Garcinia</strong> cambogia, 1 g/
kg body weight/day for 45 days (n = 6).
After the experimental period the overnight fasted
rats were sacrificed by cervical dislocation. Blood and
tissues were collected in ice-cold containers for various
estimations.
AST, ALT 11 and alkaline phosphatase 11 were estimated
in the serum. SOD 12 , CAT 13 , GSH 14 , GSH-Px 15 ,
GST 16 , LPO 17 and conjugated dienes 18 were estimated
in the liver tissue. Total cholesterol 19
phospholipids 20,21 , triglycerides 22 FFA 23 and protein 24
were estimated both in serum and tissue.

GARCINIA CAMBOGIA AND ETHANOL INDUCED PEROXIDATION
Table 2. <strong>The</strong> level <strong>of</strong> lipid peroxide, conjugated diene and activities <strong>of</strong> antioxidant enzymes in the liver <strong>of</strong> experimental groups a .
I II III IV ANOVA
Parameters b Conrol group 18% Ethanol <strong>Garcinia</strong> cambogia <strong>Garcinia</strong> cambogia + F value*
(n = 6) treated group treated group 18% ethanol treated
(n = 6) (n = 6) group (n = 6)
SOD 59.8 ± 2.56 26.4 ± 0.98*** 62.2 ± 2.34 NS 54.4 ± 1.76*** 3.68
CAT 72.6 ± 3.14 44.5 ± 3.52*** 70.8 ± 2.26 NS 66.7 ± 2.82*** 3.20
LPO 3.87 ± 0.18 7.21 ± 0.10*** 3.70 ± 0.12 NS 4.06 ± 0.09*** 2.79
Conjugated diene 74.8 ± 0.69 98.3 ± 1.14*** 73.6 ± 0.75 NS 81.2 ± 0.97*** 3.54
GST 152.6 ± 3.46 81.8 ± 2.85*** 155.4 ± 3.71 NS 151.3 ± 2.97*** 4.12
GSH-px 175.2 ± 6.82 102.7 ± 5.84*** 182.3 ± 7.06 NS 171.8 ± 5.44*** 3.96
GSH 5.11 ± 0.05 2.16 ± 0.08*** 4.89 ± 0.09 NS 4.32 ± 0.04*** 2.84
a Values are expressed as mean ± SD for 6 animals in each group
Students ‘t ’ test: Group II vs Group I, Group III vs Group I, Group IV vs Group II. ***p

90
P. MAHENDRAN AND C.S. SHYAMALA DEVI
the esterification <strong>of</strong> cholesterol in the plasma. Increase
in serum cholesterol, in the present study in
alcohol treated rats may possibly be the result <strong>of</strong>
decreased activity <strong>of</strong> this enzyme 27 .
Increase in serum triglycerides in alcohol treated rats
may be due to decreased activity <strong>of</strong> lipoprotein lipase
which is involved in the uptake <strong>of</strong> triglyceride
rich lipoprotein by extra hepatic tissue. Increased
synthesis or decreased lipid deposition or both resulted
in simultaneous accumulation <strong>of</strong> lipids in the
blood and in the liver 27 .
Ethanol induces hyperlipidemia 3,4 and hyperlipidemia
enhances lipid peroxidation 5 causing hepatotoxicity by
increasing the free radical formation which in turn increases
the level <strong>of</strong> lipid peroxides in hepatic tissue.
<strong>Garcinia</strong> cambogia containing the principal organic
acid (-)-erythro-L s -hydroxycitric acid is an <strong>effect</strong>ive
inhibitor <strong>of</strong> ATP-citrate lyase which cleaves citrate to
produce acetyl CoA. 10 (-)-hydroxycitrate suppresses
biosynthesis <strong>of</strong> both fatty acids and cholesterol in rat
hepatocytes 28,29 and in rat liver, 30 hence cholesterol
and triglyceride levels are drastically reduced in
<strong>Garcinia</strong> cambogia treated experimental rats (Group
IV). <strong>The</strong> reduction in lipids indirectly lowers the level
<strong>of</strong> peroxides due to hyperlipidemia.
<strong>The</strong> two antiperoxidative enzymes namely SOD and
CAT decreased significantly in the hepatic tissues <strong>of</strong>
alcohol administered rats suggesting the increased
damage to this tissue as a result <strong>of</strong> uncontrolled generation
<strong>of</strong> partially reduced oxygen species. <strong>The</strong> levels
<strong>of</strong> AST, ALT and alkaline phosphatase in the serum
have been elevated in ethanol treated rats suggesting
hepatotoxicity as a result <strong>of</strong> high ethanol intake
31 .
<strong>Garcinia</strong> cambogia, an <strong>effect</strong>ive antilipogenic agent 32 ,
prevents the hepatic cells to become fibrotic and the
cellular damage due to hyperlipidemia. This is evident
from the near normal activities <strong>of</strong> transferases
and ALP in the liver <strong>of</strong> <strong>Garcinia</strong> cambogia treated
group (Table 1).
Glutathione protects the hepatocytes by combining
with the reactive metabolites and thereby preventing
their covalent binding to liver protein 31 . Liver glutathione
after alcohol administration was found to decrease
due to increased utilization by the hepatocytes
because GSH seems to act as scavengers for
toxic chemical agents. <strong>The</strong> non availability <strong>of</strong> glutathione
decreases the activity <strong>of</strong> glutathione peroxidase
and glutathione transferase. Glutathione acts as the
substrate for both GSH-Px and GST. Depletion <strong>of</strong>
glutathione will render the enzymes (GSH-Px & GST)
inactive and/or less active.
It was established that the content <strong>of</strong> primary
(acylhydroperoxide) and secondary (intermolecular
“seams” in aminophospholipids) products <strong>of</strong> lipid
peroxide oxidation in blood <strong>of</strong> patients with the background
<strong>of</strong> hyperlipidemia and hypercholesterolemia
increased intensively 33 . Also in our present study the
levels <strong>of</strong> LPO and conjugated dienes increased significantly
in the ethanol administered rats suggesting
its pathogenic role. Treatment <strong>of</strong> rats with <strong>Garcinia</strong>
cambogia inhibited the deleterious process <strong>of</strong> lipid
peroxidation and maintained the levels <strong>of</strong> glutathione
to near normalcy.
<strong>The</strong> observed abnormalities in the liver and serum
may be in part due to hyperlipidemia leading to
changes in the activity <strong>of</strong> antiperoxidative enzymes,
glutathione and increased lipid peroxidation. <strong>Garcinia</strong>
cambogia modulates its antiperoxidative role by inhibiting
hyperlipidemia and peroxidation <strong>of</strong>
biomembranes which is sufficient to cause cell death
when uncontrolled.
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