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Diabetes, obesity and metabolic syndrome are becoming epidemic both in developed and developing countries in recent years. Complementary and alternative medicines have been used since ancient era for the treatment of diabetes and cardiovascular diseases. Bitter melon is widely used as vegetables in daily food in Bangladesh and several other countries in Asia. The fruits extract of bitter melon showed strong antioxidant and hypoglycemic activities in experimental condition both in vivo and in vitro. Recent scientific evaluation of this plant extracts also showed potential therapeutic benefit in diabetes and obesity related metabolic dysfunction in experimental animals and clinical studies. These beneficial effects are mediated probably by inducing lipid and fat metabolizing gene expression and increasing the function of AMPK and PPARs etc. This review will thus focus on the recent findings on beneficial effect of Momordica charantia extracts on metabolic syndrome and discuss its potential mechanism of actions.
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Review Article
Beneficial Role of Bitter Melon Supplementation in Obesity and
Related Complications in Metabolic Syndrome
Md Ashraful Alam,1Riaz Uddin,2Nusrat Subhan,3Md Mahbubur Rahman,1
Preeti Jain,1and Hasan Mahmud Reza1
1Department of Pharmaceutical Sciences, North South University, Dhaka 1229, Bangladesh
2Department of Pharmacy, Stamford University Bangladesh, Dhaka 1217, Bangladesh
3School of Biomedical Sciences, Charles Sturt University,WaggaWagga,NSW2678,Australia
Correspondence should be addressed to Md Ashraful Alam; and
Hasan Mahmud Reza;
Received  August ; Accepted  December 
Academic Editor: Xian-Cheng Jiang
Copyright ©  Md Ashraful Alam et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
Diabetes, obesity, and metabolic syndrome are becoming epidemic both in developed and developing countries in recent years.
Complementary and alternative medicines have been used since ancient era for the treatment of diabetes and cardiovascular
diseases. Bitter melon is widely used as vegetables in daily food in Bangladesh and several other countries in Asia. e fruits
extract of bitter melon showed strong antioxidant and hypoglycemic activities in experimental condition both in vivo and in vitro.
Recent scientic evaluation of this plant extracts also showed potential therapeutic benet in diabetes and obesity related metabolic
dysfunction in experimental animals and clinical studies. ese benecial eects are mediated probably by inducing lipid and fat
metabolizing gene expression and increasing the function of AMPK and PPARs, and so forth. is review will thus focus on the
recent ndings on benecial eect of Momordica charantia extracts on metabolic syndrome and discuss its potential mechanism
of actions.
1. Introduction
e prevalence of obesity is increasing at an alarming rate
health problems. It has been estimated that % of world
population will become obese by  []. Global survey
data also indicate that the prevalence of both male and
female overweight and obesity varies by region and has
rapidly increased in recent years [,]. Elements that cause
obesity involve metabolism, several genetic factors, diet, and
physical activity, as well as the sociocultural surroundings
that characterize the modern day living []. Recent evidences
suggest that high fat diet, which is also characteristic of
cafeteria type diet, as well as sedentary life style are two
contributory factors for increased trends of obese people
among the nations []. However, genetic factors contribute
to the variation of adiposity in approximately –% of a
population []. ese genetic factors thus explain the failure
of exercise and dietary regime to bring about long-term
weight loss in some individuals. Obesity can be dened as
increased energy intake than energy expenditure which ulti-
mately results in fat deposition and weight gain. According
to guidelines from the World Health Organization (WHO),
overweight in adults is dened by body mass index (BMI)
of . to ., and obesity is dened by a BMI of .
or higher [].Highbodyfatincreasestheriskofseveral
diseases such as diabetes, hyperlipidemia, and hypertension,
which may lead to arteriosclerotic disease and metabolic
syndrome []. Consequently, obesity and related cardiovas-
cular complications are also increasing alarmingly both in
developed and developing countries. Adipocyte dysfunction
and inammation contribute to the various complications
associated with obesity. Recently, adipose tissues are con-
sidered as an endocrine organ which secretes numerous fat
Hindawi Publishing Corporation
Journal of Lipids
Volume 2015, Article ID 496169, 18 pages
Journal of Lipids
and glucose regulating hormones, adipokines, and cytokines
like adiponectin, leptin, and tumor necrosis factor-𝛼(TNF-
𝛼)[,]. Increased concentration and expression of TNF-𝛼,
interleukin- (IL-), and monocyte chemoattractant protein-
 (MCP-) are evident in adipocyte dysfunction and insulin
resistance []. Furthermore, inammatory cells such as
macrophages inltration are also increased in adipose tissues
[]. Proinammatory cytokines and oxidative stress have
also been shown to be responsible for developing metabolic
disturbances, such as insulin resistance and activation of
immune response in liver, adipose tissue, and muscle [
]. Moreover, activation of inammatory pathways in hep-
atocytes is sucient to cause both local as well as systemic
insulin resistance [,].
In the last decade, much attention has been focused
on several molecular drug targets with the potential to
prevent or treat metabolic disorders. us, nuclear receptors
and their regulators have attracted much attention due
to their regulatory role in both glucose homeostasis and
lipogenesis []. Peroxisome proliferator-activated receptors
(PPARs) and liver X receptors (LXRs) are two regulatory
proteins identied to play a pivotal role in the regulation
of metabolic homeostasis [], while PPARs activation
is important for lipid metabolism, adipocyte dierentiation,
and the prevention of inammation []. PPARs also regu-
late mitochondrial biogenesis via an activator called PGC-
𝛼[,] which is physiologically regulated by exercise
[,] and calorie restriction []. In addition to these
factors, pharmacological agents such as fenobrates []
and resveratrol [] may also stimulate PGC-𝛼and restore
mitochondrial function. Recent reports suggest that natural
products are rich source of ligands for nuclear receptors
and are promising therapeutic agents in clinical practice.
Researchers have also examined the eects of various func-
tional foods on overall body composition and selective fat
depots. Water-soluble extract of Cucurbita moschata stem
( mg/kg/day for weeks) activated PPAR-𝛼,increased
𝛽-oxidation, and inhibited adipocyte dierentiation in a
dose dependent manner []. Extracts of Euonymus alatus
increased the expression of PPAR-𝛾in periepididymal fat
pad and ameliorated the hyperglycemia and hyperlipidemia
induced by high-fat diet in vivo []. Acacia polyphenols
increased the mRNA expression of fat metabolizing genes
like PPAR-𝛼and PPAR-𝛿in skeletal muscle and lowered
the expression of fat acid synthesis-related genes (SREBP-c,
ACC, and FAS) in the liver []. Green tea catechins have also
been proposed as therapeutic agents for body fat reduction
Bitter melon (Momordica charantia L.) is widely used for
the treatment of diabetes. Recent research reports suggest that
bitter melon extracts may ameliorate high fat diet induced
obesity and hyperlipidemia in animal model. Most ndings
related to obesity and hyperlipidemia also showed that the
plant extracts may modulate fat metabolizing kinases such
as AMPKs, genes, and nuclear factors like PPARs, LXRs, and
PGC-𝛼, in liver and skeletal muscle and aected adipocyte
dierentiation, while several review papers suggest the antidi-
abetic mechanism [] and various pharmaceutical eects of
the plant [] and emphasized its ecacy and safety aspects.
F : Fruits of dierent variety of Momordica charantia available
in Bangladesh. Upper le one is commonly known as Korolla and
right one as Ucche.
erefore, the present review aims to describe the eect of
bitter melon extracts on various parameters of metabolic
syndrome, obesity, and related cardiovascular complications.
anisms responsible for antiobesity and hypolipidemic eects
of the plant based on available information to date.
2. Bitter Melon Overview and Traditional
Medicinal Uses
Bitter melon is a climbing shrub cultivated mainly in
Bangladesh, India, China, and Korea, mostly in Asian coun-
tries. e plant also grows in tropical areas of Amazon, East
Africa, and the Caribbean. It belongs to family Cucurbitaceae
and the scientic name is Momordica charantia. Generally,
two varieties of the plant are found in Bangladesh, while the
small size one is locally called “Ucche”andthelargesize
one is locally known as “Korolla”(Figure). However, some
that include M. balsamina L., M. foetida Schum., and M.
rostrata A. Zimm. Bitter melon fruits are taken as culinary
vegetable in Bangladesh and in Indian subcontinent; it is also
used as a traditional medicinal plant for the treatment of
various diseases in Bangladesh as well as other developing
countries like Brazil, China, Colombia, Cuba, Ghana, Haiti,
India Mexico, Malaya, Nicaragua, Panama, and Peru [].
Perhaps the most common traditional use of the plant is
to treat diabetes in dierent countries around the globe. It
conditions such as dysmenorrhea, eczema, emmenagogue,
galactagogue, gout, jaundice, kidney (stone), leprosy, leucor-
[]. Momordica charantia arealsodocumentedtopossess
abortifacient, anthelmintic, contraceptive, antimalarial, and
laxative properties [].
Recent scientic exploration on this plant elucidated
potential biological eect on both animal and clinical studies.
Apartfromitspotentialantibacterial[] and antiviral activi-
ties [], bitter melon extracts are also eective against cancer
and were found to be eective for the treatment of ulcer,
malaria, pain and inammation, psoriasis, dyslipidemia, and
hypertension. Momordica charantia also contains biologically
active chemical compounds such as glycosides, saponins,
Journal of Lipids
alkaloids, xed oils, triterpenes, proteins, and steroids [].
Several other biologically active chemical constituents have
so far been isolated from dierent parts of the plant, including
the leaves, fruit pulp, and seeds.
Typical Recipe of a Bitter Melon Dish Popular in Bangladesh
Bitter Melon Fry with Potato. Ingredients are as follows:
bitter melon (nely chopped):  g,
potato (nely chopped): - (whole potato),
onion:  full (nely chopped),
garlic paste: half table spoon,
hot chilli:  pieces,
curcuma powder: half table spoon,
oil (soyabean): - table spoon full,
salt: (q.s.t).
First fry the chopped onion, garlic, and chilli together
with soyabean oil in a cocking pan. Add some curcuma
powder and salt and fry gently. Aer nishing this stage, add
the potato and melon get brown color on its surface and a nice
smell will come out from the dish. Serve it with warm rice
or paratha bread made up of our, having layers and fried in
vegetable oil.
3. Chemical Constituents Isolated from
Bitter Melon
M. charantia containsanumberofchemicalsubstances
including nutritionally important vitamins, minerals, antiox-
idants, and many other phytochemicals, that is, glycosides,
saponins, phenolic constituents, xed oils, alkaloids, reducing
sugars,resins,andfreeacids[]. e immature fruits are
also good source of vitamin C and also provide vitamin A,
phosphorus, and iron []. Depending on the characteristics
several groups such as phenolic and avonoid compounds,
cucurbitane type triterpenoids, cucurbitane type triterpene
glycoside, oleanane type triterpene saponins, and insulin like
3.1. Phenolic and Flavonoids Compounds. Phenolic com-
pounds isolated from M. charantia are gallic acid, tannic
acid, (+)-catechin, caeic acid, p-coumaric, gentisic acid,
chlorogenic acid, and epicatechin []. Figure illustrates
the phenolic constituents which have been isolated from M.
charantia using high performance liquid chromatography
(HPLC) analysis.
3.2. Cucurbitane Type Triterpenoids. e terpenoids are iso-
prenoids derived from ve carbon isoprene units. e cucur-
bitacins are a typical group of cucurbitane type triterpenoids
found mainly in cucumber family (Cucurbitaceae). e main
chemical constituents of M. charantia are cucurbitane type
triterpenoids [] including charantin [], dierent
Caeic acid Ferulic acid Gallic acid
p-coumaric acid (+)-catechin acid
F : Dierent phenolic compounds isolated from M. charan-
kuguacins [], momordicin, and karavilagenins []. Fig-
ure represents the chemical structures of the triterpenoids
found in the plant.
3.3. Cucurbitane Type Triterpene Glycoside. Cucurbitane gly-
cosides isolated from M. charantia are charantosides I–VIII
[]; momordicosides F, F, G, I, K, L, M, N, O, Q, R, S,
and T []; karavilosides I, II, III, IV, V, VI, VII, VIII, IX,
X,andXI[]. Other cucurbitane type triterpene glycosides
include -O-𝛽-D-allopyranosyl, 𝛽, -dihydroxycucurbita-
, and (E)-diene--al []; -O-𝛽-D-allopyranosyl, 𝛽,-
dihydroxy cucurbita-(), (E)-diene--al, -O-𝛽-D-allo
pyranosyl, -methoxy cucurbita-(), and (E)- diene--
ol []; goyaglycoside-a, -b, -c, -d, -e, -f, -g, and -h [].
Cao et al. recently isolated and identied new cucurbi-
tane triterpenes, 𝛽,-epoxy-cucurbita-,E,-trien-𝛽-
ol, from acid-treated ethanol extract of the plant [].
dantly present in Momordica genus and have been isolated
from M. charantia, are presented in Figure .
3.4. Oleanane Type Triterpene Saponins. Several oleanane
type triterpene saponins such as soyasaponins I, II, and
III have been isolated from the fresh fruit of Japanese M.
Charantia [].
3.5. Peptides. Recently two novel peptides, MCh- and MCh-
, have been isolated from the seeds of bitter melon [].
4. Effect of Bitter Melon on Body Weight,
Obesity, and Adipocyte Dysfunction
Body weight gain and abdominal fat deposition are the
early signs of obesity. Bitter melon extract showed useful
benet on body weight gain and fat deposition (Figure ,
Table ). Several investigational reports suggest that bitter
melon can reduce body weight in high fat diet induced
obesity in laboratory animals. Bitter melon (.% of diet)
Journal of Lipids
Kuguacin A
Kuguacin B Kuguacin C
Kuguacin D
Kuguacin E Kuguacin F
Kuguacin G
Kuguacin H
Kuguacin I
Kuguacin J
Kuguacin K
Kuguacin M
Kuguacin N
Kuguacin O
Kuguacin P
Kuguacin Q
Kuguacin R
Kuguacin S
Momordicine I
Karavilagenin A
Karavilagenin B
Karavilagenin C
Kuguacin L
F : Chemical structure of some cucurbitane triterpenoids isolated from M. charantia.
supplementation prevented the body weight gain and visceral
fat mass signicantly in rats fed high fat diet []. is
weight reduction may be a result of increased fatty acid
oxidation which ultimately facilitates weight reduction [].
Moreover, the bitter melon extract supplementation reduced
the peritoneal fat deposition in rats fed a high fat diet [].
In another study, bitter melon signicantly decreased the
weights of epididymal white adipose tissue (WAT), visceral
Journal of Lipids
15,16-Dihydroxy-alpha-eleostearic acid
Momordicoside A:
Momordicoside B:
Momordicoside C
Momordicoside E
Momordicoside D
Charantosides I
Charantosides II
Momordicoside K: R =Me
Momordicoside L: R =H
Momordicoside F1:
R1=Me, R2=𝛽-D-glucopyranosyl
Momordicoside F2:
R1=H, R2=𝛽-D-allopyranosyl
Momordicoside G:
R1=Me, R2=𝛽-D-allopyranosyl
Momordicoside I :
R1=H, R2=𝛽-D-glucopyranosyl
Charantosides III:
Charantosides IV:
Charantosides V:
Charantosides VI:
Karaviloside I:
R1=Me, R2=𝛽-D-glucopyranosyl
Karaviloside II:
R1=Me, R2=𝛽-D-allopyranosyl
Karaviloside III:
R1=H, R2=𝛽-D-allopyranosyl
Karaviloside IV:
R1=𝛽-D-glucopyranosyl, R2=H
Karaviloside V:
R1=H, R2=𝛽-D-glucopyranosyl
R1=H, R2=𝛽-D-allopyranosyl
R1=Me, R2=𝛽-D-glucopyranosyl
R1=Me, R2=𝛽-D-allopyranosyl
F : Chemical structure of major cucurbitane glycosides isolated from M. charantia.
Journal of Lipids
T : Eect of bitter melon on body weight, obesity, and adipocyte dysfunction.
Model Dose Experimental outcome Reference
HF diet induced fat
.% and .%
(i) Decreased body weight, visceral fat mass, plasma glucose, and TAG.
(ii) Increased plasma catecholamines. []
HF diet induced fat
.% and .%
(i) Decreased body weight, visceral fat mass, plasma glucose, and TAG.
(ii) Increased adiponectin.
(iii) Increased UCP  in BAT and UCP  in red gastrocnemius muscle.
(iv) Increased expression of the transcription coactivator PGC-𝛼both in BAT and
in gastrocnemius muscle.
Male CBL/J
mice,  weeks old
. g/kg/day,
. g/kg/day P
extracts, or .,
. g/kg/day G
(i) Decreased body weight and visceral fat mass.
(ii) Decreased plasma glucose, TG, and total cholesterol (TC) but increased free
fatty acid (FFA).
(iii) Increased mRNA expression of leptin, PPAR-𝛾,PPAR-𝛼, and decreased
expression of resistin.
Male Wistar rats
fed HF diet % (w/w) powder
(i) Decreased body weight and adipose tissues.
(ii) Decreased TAG and cholesterol.
(iii) Increased adiponectin.
Over weight rats Aqueous extract
 mL/day
(i) Reduced elevated body weight and cholesterol, TG, and low-density lipoprotein
cholesterol (LDL-C).
(ii) Increased high density lipoprotein cholesterol (HDL-C).
HF diet fed male
(i) Decreased body weight, retroperitoneal, epididymal, and inguinal fat deposition
and adipocyte diameter.
(ii) Increased phosphorylation of acetyl-CoA carboxylase, cAMP-activated protein
(iii) Increased TNF-𝛼concentration in the WAT accompanied by TUNEL-positive
T-L cells (i) Decreased lipid accumulation and intracellular TGs. []
Primary human
(i) Inhibited adipocyte dierentiation by reducing PPAR𝛾,SREBP,andperilipin
mRNA gene expression.
(ii) Increasing lipolysis in preadipocytes.
fat, and the adipose leptin and resistin mRNA levels in
CBL/J mice fed with a high-fat (HF) diet []. Bano et
al. reported that  mL/day dose of aqueous extract of bitter
melon signicantly reduced body weight gain in rats []. A
recent study also showed that the seed oil supplementation of
the plant reduced body weight and fat mass in mice fed a high
fat diet [].
Several mechanisms for lowering fat mass in obesity
have been proposed. Generally, increased fatty acid transport
would facilitate fat burning in tissues. Carnitine palmitoyl-
transferase (CPT) system is the predominant system for
transporting the fatty acid to mitochondrial matrix []. Two
CPT- resides on the inner surface of the outer mitochondrial
membrane and is a major site of regulation of mitochondrial
oxidation in skeletal muscle due to the reduced expression
and activity of CPT system in human and animal [].
Earlier investigations also suggest that inhibition of CPT-
with the chemical etomoxir increases lipid deposition and
exacerbates insulin resistance when animals are placed on
aHFdiet[], whereas overexpression of CPT- improved
lipid-induced insulin resistance []. Additionally, increased
skeletal muscle CPT- protein expression is sucient to
increase fatty acid oxidation and to prevent HF diet-induced
fatty acid esterication into intracellular lipids, subsequently
[]. Bitter melon supplementation in these rats signicantly
decreased the body weight gain by increasing the hepatic and
muscle mitochondrial carnitine palmitoyltransferase-I (CPT-
) and acyl-CoA dehydrogenase enzyme [].
Mitochondrial uncoupling is another process in mito-
chondria whereby most of the energy consumed will be
ton gradient generated for the ATP synthesis is consumed
through specied protein function known as uncoupling
proteins which are attaining interest in recent years because of
their critical role in energy expenditure and lipid metabolism
[]. Several uncoupling proteins have been isolated, that
is, UCP, UCP, UCP, UCP, and UCP. ese proteins
are distinctively expressed in several tissues and primarily
participate in proton leaking. Alteration in function of these
proteins will be benecial in weight reduction in obesity
[]. In mice, genetic manipulation of UCP in skeletal
muscle suggests that this protein is involved in the regulation
of energy expenditure []. UCP in brown adipose tissue
(BAT) and UCP in red gastrocnemius muscle were increased
due to bitter melon supplementation followed by increased
expression of the transcription co-activator PGC-𝛼,akey
regulator of lipid oxidation [].
Adipose tissues also play a central role in obesity. Bitter
melon supplementation prevented the adipocyte hypertrophy
Journal of Lipids
- Increased PPAR-𝛼and PPAR-𝛾expression
- Increased expression of the transcription
coactivator PGC-1𝛼
- Increased 𝛽-oxidation
- Decreased fatty acid synthesis
- Decreased fat
- Increased insulin secretion
- Prevents 𝛽-cell damage
- Increased PPAR-𝛼and PPAR-𝛾
expression in skeletal muscle
Fat cells
- Inhibited adipocyte hypertrophy
- Inhibited adipocyte dierentiation
- Increased PPAR-𝛾expression
- Increased expression of the
transcription coactivator PGC-1𝛼
- Decreased visceral fat mass
F : Eect of bitter melon on various organ and probable molecular targets for improving obesity and diabetes.
in rats fed HF diet []. Its supplementation suppressed the
visceral fat accumulation and inhibited adipocyte hypertro-
acetyl-CoA carboxylase-, lipoprotein lipase, and adipocyte
fatty acid-binding protein, downregulating lipogenic genes
in adipose tissues []. A recent study suggests that bitter
melon seed oil may increase the adipocyte death by cAMP-
activated protein kinase (PKA) mediated apoptosis in white
adipose tissues (WAT) of HF diet fed mice []. Previous in
vitro study also showed prevention of preadipocyte dier-
entiation and lipid accumulation in adipocyte by the plant
extract. Bitter melon treatment of T-L cells resulted in
a decreased lipid accumulation and signicantly decreased
intracellular triglyceride (TG) amount compared to untreated
control cells []. Moreover, bitter melon reduced the lipid
accumulation during dierentiation from a preadipocyte
to adipocyte and downregulated PPAR𝛾[]. PPAR𝛾is
considered the master regulator of adipogenesis during dif-
ferentiation of preadipocyte to adipocyte []. Other adi-
pogenic transcription factors include the CCAAT/enhancer
binding proteins (C/EBP𝛼,C/EBP𝛽,andC/EBP𝛿)andsterol
regulatory element-binding protein c (SREBP-c) []. Bitter
melon juice inhibited adipocyte dierentiation by reducing
PPAR𝛾, SREBP, and perilipin mRNA gene expression and by
increasing lipolysis in primary human adipocyte [].
5. Effect of Bitter Melon on Dyslipidemia
Dyslipidemia are disorders related to increased cholesterol
synthesis and abnormal lipoprotein metabolism, including
lipoprotein overproduction and deciency which are the
early manifestations of obesity. Plasma lipids such as choles-
terol, fatty acids, and TG concentrations are increased due to
diabetes and HF diet feeding in laboratory animal and human
[]. Dyslipidemia is widely accepted as independent risk
factor for coronary heart disease and associated with insulin
resistance in type  diabetes mellitus []. e main cause
of increased cholesterol and TGs in diabetic dyslipidemia is
the increased FFA release from insulin-resistant fat cells [].
us, FFAs overload into the liver and increased glycogen
stores promote TG production, which in turn stimulates
the secretion of apolipoprotein B (ApoB) and very low-
density lipoprotein (VLDL) cholesterol [,]. e hepatic
overproduction of VLDL appears to be the primary and
crucial defect of the insulin resistant accompanying obesity.
Bitter melon extracts showed lipid lowering eect both
in diabetic and HF diet fed rats (Table ). Bitter melon
in dietary cholesterol fed rats []. However, the bitter
melon extract showed little eect on serum lipid parameters
but increased HDL-C both in the presence and absence of
dietary cholesterol in rats []. Ahmed et al. reported that
 weeks of supplementation of the plant extract normalized
the increased plasma nonesteried cholesterol, TGs, and
phospholipids in streptozotocin- (STZ-) induced diabetic
rats []. Treatment for  days with Momordica charantia
fruit extract to diabetic rats also decreased TG and LDL
and increased HDL level signicantly []. Chen and Li also
reported that .% bitter melon extracts supplementation
reduced the plasma cholesterol in rats fed a HF diet [].
Another study showed that bitter melon reduced TG and LDL
levels and increased HDL levels in high sucrose fed rats [].
Ground bitter melon seeds (.% wt/wt) decreased TC and
LDL-C and increased HDL-C in female Zucker rats []. e
plant supplementation also decreased plasma level of TG,
cholesterol, and FFA in plasma of ospring rats fed a HF
diet []. Oishi et al. reported that saponin fraction of the
plant decreased the TAG and pancreatic lipase activity in corn
oil loaded rats []. Decreased pancreatic lipase activity is
particularly important in fat absorption from gut wall as it
enhances the fat digestion to fatty acids and increased plasma
Journal of Lipids
T : Eect of bitter melon extracts on lipid parameters of diabetic and obese animal models.
Model Dose Experimental outcome Reference
Cholesterolfedrats .,and%ofdiet (i) Not changed TC level, but
(ii) increased HDL-C level in plasma. []
diabetic rats
 mL % fruit
extract per kg body
weight daily for 
(i) Decreased elevated level of plasma cholesterol, TGs and phospholipids in STZ
induced diabetic rats. []
Diabetic rats (i) Decreased in TG and LDL,
(ii) Increased in HDL. []
Rats fed a HF diet . g/kg or .%
(i) Supplementation did not aect serum and hepatic cholesterol.
(ii) Supplementation in HF diet rats led to a lowering of hepatic TAG and steatosis
score in liver section.
(iii) Plasma epinephrine and serum FFA concentrations were increased.
(iv) Lowered TAG concentration in red gastrocnemius and tibialis anterior.
Wistar rats
Saponin fraction
(– mg/kg body
(i) Decreased pancreatic lipase activity and serum TG level in corn oil loaded rats. []
Female CBL/
mice fed with HF
.% freeze-dried BMJ
with diet
(i) Normalized plasma TAG, cholesterol, and NEFA.
(ii) Normalized AST, ALT, and ALP in plasma.
(iii) Decreased ApoB secretion and modulated the phosphorylation status of IR and
its downstream signalling molecules.
Albino rats fed
with sucrose
, , and  mg/kg
of body weight
(i) Reduced TG and LDL levels and increased HDL levels.
(ii) Normalized hyperglycemia.
(iii) Lowered TBARS and normalized levels of reduced glutathione.
Ospring rats fed
high (%)
fructose diet
% of diet
(i) Decreased plasma level of TG, cholesterol, and FFA.
(ii) Lowered the hepatic levels of stearoyl-CoA desaturase and microsomal TG
transfer protein mRNA.
(iii) Increased PPAR𝛾coactivator -𝛼and broblast growth factor  mRNA and
fatty acid binding protein .
Female Zucker rats .% (wt = wt)
ground BMS
(i) Supplementation increased the expression of PPAR-𝛾in the WAT.
(ii) Decreased TC and LDL-C; increased HDL-C.
(iii) Downregulated the expression of PPAR-𝛾, nuclear factor-kB (NF-kB), and
interferon-𝛾mRNA in heart tissue.
HF diet fed mice .% plant extract
(i) Decreased TC, TGs, and LDL-C.
(ii) Increased hepatic AMPK p, AMPK 𝛼AMPK𝛼, and Sirt content.
(iii) FGF and insulin concentrations were signicantly decreased.
(iv) Hepatic FGF content was signicantly downregulated, while FGF receptors ,
, and  (FGFR, FGFR, and FGFR) were greatly upregulated.
Wistar rats fed
high cholesterol
(i) Decreased serum TC and LDL-C HDL-C.
(ii) Decreased mRNA levels of hepatic LXR𝛼in rats.
(iii) Increased the hepatic CYPA mRNA level.
CBL/J mice
% HF diet
., ., and
. g/kg/day extracts
(i) Decreased serum TC and fatty acids.
(ii) Normalized leptin and insulin concentration.
(iii) Increased PPAR𝛼level in liver.
(iv) Increased GLUT expression in skeletal muscle.
(v) Signicantly increased the hepatic protein contents of AMPK phosphorylation
and decreased expression of phosphoenolpyruvate carboxykinase (PEPCK).
fatty acid level aer fat intake. us reduction of pancreatic
lipase would be a crucial target for lowering circulating FFAs.
e molecular mechanisms behind the lipid lowering
eect of bitter melon extracts are revealed only recently.
Freeze-dried bitter melon juice (.%) with diet normalized
plasma TAG, cholesterol, and NEFA in female CBL/ mice
fed a HF diet []. In this study, the juice in diet also decreased
ApoB secretion and modulated the phosphorylation status of
insulin receptor (IR) and its downstream signalling molecules
[]. Insulin resistance and dyslipidemia are characterized
by signicant downregulation of hepatic insulin signalling
as documented by attenuated phosphorylation of IR and
IR substrates (IRS) []. A direct link between attenuated
hepatic insulin signalling and synthesis and secretion of
VLDL apoB was established before []. VLDL particles
are mainly cleared from circulation by the LDL receptor
(LDLR), also referred to as apoB/E receptor. e transcription
of the LDLR gene is regulated by intracellular cholesterol
Journal of Lipids
concentration, hormones, and growth factors. Moreover,
sterol regulatory element binding protein- (SREBP-) is
selectively involved in the signal transduction pathway of
insulin and insulin-like growth factor-I (IGF-I) leading to
LDLR gene activation contributing to the delayed VLDL
particle clearance associated with obesity causing insulin
resistance []. Transcription factors in the SREBP family are
key regulators of the lipogenic genes in the liver.
way of increasing lipid metabolism and utilization in energy
demanding cells and tissues. Mitochondrial biogenesis is
regulated via several transcriptional regulatory factors like
AMPK, PPAR-𝛾, and PGC-𝛼[,]. AMPK regulated
PPAR-𝛾and PGC-𝛼activation stimulated most of the
transcriptional signal to increase fatty acid oxidation and
mitochondrial function []. Bitter melon supplemen-
tation increased PPAR𝛾coactivator -𝛼(PGC  𝛼)and
broblast growth factor  mRNA and fatty acid binding
protein  in ospring of HF diet fed rats []. PGC- family
of coactivator is of particular importance in the control
of liver metabolism []. PGC-𝛼stimulates mitochondrial
biogenesis and respiration in multiple cell types and modu-
lates biological programs normally associated with increased
oxidative metabolism []. is PGC-𝛼activation and
upregulation by bitter melon supplementation also decreased
plasma level of TGs, cholesterol, and FFA in plasma of
ospring rats fed a HF diet []. Recent investigation also
reported that .% bitter melon extract supplementation
signicantly increased hepatic AMPK p, AMPK 𝛼, AMPK
𝛼, and Sirt content in HF diet fed mice []. AMP-activated
protein kinase (AMPK) is a cellular fuel gauge, maintaining
intracellular energy balance in mammalian cells []. AMPK
activation is necessary for the transcriptional regulation of
energy demand. Mice expressing a dominant-negative form
of AMPK failed to increase mitochondrial biogenesis in
response to energy deprivation in skeletal muscles [].
In contrast, lipid oxidation and mitochondrial activity were
increased in mice over expressing the phosphorylated AMPK
[,]. us, AMPK activation followed by Sirt due
to the plant extract supplementation decreased TC, TGs,
and LDL-Cin HF diet fed mice []. Bitter melon extract
supplementation also decreased serum TC and fatty acids
in CBL/J mice % high-fat (HF) diet []. is lipid
lowering eect is attributed to its ability to increase AMPK
phosphorylation and PPAR𝛾mediated lipid metabolism in
liver [].
e plant extract supplementation also decreased mRNA
levels of hepatic LXR𝛼andincreasedthehepaticCYPA
mRNA level in rats []. LXRs were rst identied as
orphan members of the nuclear receptor super family and
oxidized derivatives of cholesterol act as ligands for the LXRs.
LXR also plays an important role in lipid and cholesterol
metabolism. LXR𝛼knockout mice develop enlarged fatty
livers, degeneration of liver cells, high cholesterol levels in
liver, and impaired liver function when fed a high-cholesterol
diet []. Hepatic LXR𝛼downregulation due to bitter melon
extract supplementation also decreased serum TC and LDL-
C HDL-C in Wistar rats fed high cholesterol diet [].
6. Effect of Bitter Melon on Nonalcoholic Fatty
Liver and Liver Diseases
Hepatoprotective eect of bitter melon extracts is mainly
attributed to its antioxidant capacity to scavenge free radicals
and reduced inammation in liver due to noxious stimuli.
Chaudhari et al. reported that hydroalcoholic extract of the
plant leaves ( and  mg/kg) normalized the levels of
ALT, A S T, AL P, an d t o t al b i li r ub i n an d p r e ve n t e d st e at o s is ,
centrilobular necrosis, and vacuolization in liver of carbon
tetrachloride induced liver damage in rats []. ALT, AST,
and ALP are liver enzymes that signicantly increased due
e study by enmozhi and Subramanian also conrmed
the antioxidant and hepatoprotective potential of its fruit
extract in ammonium chloride-induced toxicity in rats [].
Fruit extract ( mg/kg) of the plant normalized the ele-
vated TBARS, hydroperoxides, and liver markers (alanine
transaminase, ALT; aspartate transaminase, AST; and alka-
line phosphatase, ALP) and increased the levels of glutathione
peroxidase (GPx), superoxide dismutase (SOD), and catalase
and reduced glutathione in ammonium chloride-induced
toxicity in rats []. e plant extract at a dose of  mL/kg
also produced signicant protection of liver damage due to
high dose of acetaminophen administration in rabbits []. A
recent study also suggests that bitter melon supplementation
ameliorates oxidative stress in liver of fructose fed ospring
of rats by improving the antioxidant enzymes activity such as
GPx, SOD, and catalase [].
Liver is the rst line organ which undergoes direct chal-
lenges during diet induced obesity and diabetes. Excess fat
intake overwhelms the hepatic tissues to metabolize them and
undergoes fatty acid mediated inammation and oxidative
stress []. Excess fat accumulation in liver can be a result of
one or a combination of the following metabolic alterations:
(a) decreased 𝛽-oxidation of fatty acids, (b) increased fatty
acid synthesis due to up-regulation of lipogenic pathways,
(c) increased delivery of fatty acids from adipose and other
organs due to lipolysis, and (d) inhibition of VLDL-TG export
[]. Numerous studies indicated that high fat and fructose
overconsumption leads to the development of metabolic
syndrome, including insulin resistance, dyslipidemia, and
hypertension in humans [,]andanimals[,].
High fat diet also develops hepatic steatosis in animal by
accumulating lipid in hepatic tissues []. Bitter melon
supplementation reduced the fat accumulation in liver and
prevented steatosis in mice fed a high fat diet []. In this mice
model, high fat diet feeding caused upregulation of broblast
growth factor  levels in liver []. FGF family plays valuable
role in the development of NAFLD []. It has been shown
that plasma FGF levels were increased in patients with
insulin resistant type  diabetes mellitus (TDM) and in
NAFLD patients who have high level of hepatic triglycerides
(TG) [,]. e plant supplementation downregulated
hepatic FGF content signicantly and increased hepatic
phosphorylated AMPK, AMPK 𝛼, AMPK 𝛼, and Sirt
content compared to the high fat diet fed mice [].
 Journal of Lipids
7. Effect of Bitter Melon on Diabetes
Mostly reported biological activities of bitter melon are the
eect on diabetes and hyperglycaemia. e plant showed
potent antihyperglycemic eect in various animal models.
An aqueous extract of bitter melon in normal mice lowered
the glycaemic response to both oral and intraperitoneal
Aqueous and alkaline chloroform extracts also reduced the
hyperglycaemia in diabetic mice []. Pulp juice of this
plant lowered fasting blood glucose and glucose intolerance
in NIDDM model rats, while no eect was seen in STZ
treated IDDM model rats []. In alloxan induced diabetic
rats, blood sugar level was lowered aer  weeks of treatment
with aqueous extract of bitter melon fruits []. e plant
extract also improved glucose intolerance in STZ treated
diabetic rats and increased the glycogen synthesis in liver
[]. e aqueous extract powder of fresh unripe whole
fruits at a dose of  mg/kg body weight reduced fasting
blood glucose by % which is comparable to the eect of
glibenclamide, a well-known oral antidiabetic drug, in rats
[]. Acute oral administrations of the whole plant extract
also caused dose-related signicant hypoglycaemia in normal
(normoglycaemic) and STZ-treated diabetic rats []. M.
charantia extract also improved insulin sensitivity, glucose
tolerance, and insulin signalling in high fat diet-induced
insulin resistance rats []. M. charantia also maintained the
normal glucose concentration in chronic sucrose loaded rats
Improvement of hyperglycaemic condition in experi-
mental animal by M. charantia extracts has many plausible
mechanisms, that is, (a) prevention of glucose absorption in
the alimentary canal, (b) enhancing the glucose uptake by
tissues, (c) increasing glucose metabolism, and (d) enhancing
insulin like action and pancreatic beta cell stimulation [].
Oral administration of the plant juice signicantly reduced
the Na+/K+- dependent absorption of glucose from the
intestinal mucosa in STZ-induced diabetic rats []which
were also observed in vitro []. Moreover, these extracts
may also inhibit carbohydrate metabolizing enzymes like
alpha-amylase, alpha-glucosidase, and pancreatic lipase and
hence limits the absorption of glucose through gut wall [
]. Several authors reported that the plant extract improves
glucose uptake in cells, thereby increasing the glucose
metabolism. Oral supplementation of the plant increased the
muscle content of facilitative glucose transporter isoform 
(GLUT) proteins which might be responsible for signicant
improvement of oral glucose tolerance in KK-Ay mice, an
animal model with type  diabetes with hyperinsulinemia
[]. Similar results were also rep orted by other investigators.
Shih et al. reported that bitter melon extract signicantly
increases the mRNA expression and GLUT in skeletal
muscle and normalized fructose diet-induced hyperglycemia
in rats [].
In vitro study suggested that the fresh juice of the plant
increased the uptake of amino acids and glucose in L
myotubes []. Aqueous and chloroform extracts of this
fruit also increased glucose uptake and upregulated GLUT-
, PPAR-𝛾, and phosphatidylinositol- kinase (PIK) in L
myotubes []. e eects of the plant on glucose uptake
and adiponectin secretion were also reported in adipose cells,
T-L adipocytes. Water-soluble components of the plant
enhanced the glucose uptake at suboptimal concentrations of
insulin in T-L adipocytes [].
M. charantia showed benecial eect in diabetes by
maintaining normal glucose levels and several investigators
suggested that this benecial eect is attributed to its ability
to maintain the structural integrity of the pancreatic islets
of hormones []. An investigation was carried out
to observe the eect of Momordica charantia fruit juice on
the distribution and number of 𝛼,𝛽,and𝛿cells in the
pancreas of STZ-induced diabetic rats and it was found
that the juice signicantly increased the number of 𝛽cells
compared with untreated diabetic rats []. However, 𝛼-
cells did not change signicantly compared with untreated
diabetic rats in this study. Oral administration of the seed
extracts at a dosage of  mg/kg body weight for  days
prevented degeneration of pancreatic islets and restored islets
function []. Acetone extract of the plant fruit powder at
doses , , and  mg/kg body weight aected dierent
phases of recovery of 𝛽-cells of the islets of Langerhans
and normalizes the functioning of the concerned cells [].
Moreover, the fruit powder extracts enhanced neoformation
of islets from preexisted islet cells along acinar tissues [].
A recent report also suggests that administration of ethanolic
extract of the fruit pulp of the plant in neonatal STZ-
induced type  diabetic rats increased the islet size, total 𝛽-
cell area, number of 𝛽-cells, and insulin levels compared with
untreated diabetic rats [].
Other scientists also reported insulin secretagogue prop-
erties of the plant as well. Subcutaneous administration of
the protein extract isolated from Momordica charantia fruit
pulp increased plasma insulin concentrations by -fold aer
 h of administration []. e fruit pulp protein extract
also increased the insulin secretion but not glucagon in
perfused rat pancreas []. A recent report also suggests
that saponin signicantly stimulated insulin secretion in vitro
from pancreatic MIN 𝛽-cells [].
Apart from these eects, M. charantia has also been
reported to improve the sensitivity of insulin in hyperin-
sulinemia. Bitter melon supplementation improved insulin
resistance and lowered serum insulin and leptin to the high
fat diet fed rats []. It improves insulin sensitivity in skeletal
muscle by increasing skeletal muscle insulin-stimulated IRS-
tyrosine phosphorylation in high-fat-fed rats []. A recent
report further conrmed that polypeptide isolated from the
plant binds with IRs and modulates downstream insulin
signalling pathways [].
8. Effect of Bitter Melon on Hypertension and
Vascular Dysfunction
Hypertension and vascular dysfunction are two metabolic
disorders that occur during the progression of obesity and
metabolic syndrome and most of the obese people are
Journal of Lipids 
T : Clinical studies of bitter melon (MC).
Study design Subject Dose and duration Outcome Reference
Case study
 moderate noninsulin
dependent diabetic (NIDDM)
Aqueous homogenized
suspension of the vegetable pulp
Signicant reduction of both
fasting and postprandial serum
glucose levels was observed
Case study  patients of either sex (–
years of age) of NIDDM
 mg twice dailywith  days
treatment plus half doses of
metformin or glibenclamide or
both in combination
e extract acts in synergism
with oral hypoglycemics and
potentiates their hypoglycemia in
 patients,  years old and
Two c apsu l es of M. charantia
three times a day aer meals, for
No signicant eect on mean
fasting blood sugar, total
cholesterol, and weight or on
serum creatinine, ALT, AST,
sodium, and potassium
active-control trial
e total of  patients were
enrolled into the study; 
patients were randomized to the
either metformin (𝑛=33), bitter
melon  mg/day (𝑛=33),
bitter melon  mg/day
(𝑛=32), or bitter melon
 mg/day (𝑛=31)
Bitter melon   mg/day,
 mg/day, and  mg/day or
metformin  mg/day for four
 mg/day dose showed
signicant decline in
fructosamine at week 
 and   mg/day did not
signicantly decrease
fructosamine levels
supplementation trial
 eligible ( men and 
women) with a mean age of
. ±. years ( to  years)
. gram lyophilized bitter melon
powder in capsules daily for
three months
e metabolic syndrome
incidence rate decreased
compared to that at baseline
e waist circumference also
signicantly decreased aer the
Two-arm, parallel,
 type  diabetic patients taken
fruit pulp and  type  diabetic
patients taken as placebo
 g/day of MC dried-fruit pulp
containing . ±. mg of
Signicant decline of total
advanced glycation end-products
(AGEs) in serum aer  weeks
of the intervention
observed to develop moderate to high blood pressure. Whole-
plant aqueous extract of the plant dose dependently normal-
ized the hypertension in hypertensive Dahl salt-sensitive rats
probably followed by acetylcholine mediated pathways [].
A recent investigation also showed that M. charantia extracts
lowered elevated blood pressure in Wistar rats aer L-NAME
challenge on  days []. Moreover, the plant extracts also
reduced the angiotensin converting enzyme activities [].
However, frustrating results were also observed in clinical
setup. Recently, a preliminary open-label uncontrolled sup-
plementation trial was conducted in  people with a mean
age of . ±. years who were supplemented with .
lyophilized encapsulated Momordica charantia powder daily
for three months []. But no signicant dierences were
noted in this study for high blood pressure, heart rate, and
other parameters of metabolic syndrome [].
9. Antioxidant Activity of Bitter Melon
Bitter melon showed potent antioxidant activities both in
vitro and in vivo as several investigators reported the antiox-
to fruits. Aqueous and methanolic extracts of bitter melon
showed increased metal chelating activity, prevented lipid
peroxidation, and inhibited free radical generation in xan-
thine oxidase and cytochrome C mediated in vitro system
scavenge the DPPH free radicals and increased ferric reduc-
ing power, while fruits extracts scavenge hydroxyl radicals
andshowedincreasedtotalantioxidantcapacity[]. Phe-
nolics extracted from pericarp and seed of the plant at three
maturity stages also showed DPPH free radical scavenging
activity []. Phenolic compounds isolated from the bitter
melon are catechin, gallic acid, ferulic acid, p-coumaric acid,
gentisic acid, chlorogenic acid, and epicatechin [,].
e antioxidant activity of the total aqueous extract
and total phenolic extract of Momordica charantia fruits
was assessed in rat cardiac broblasts (RCFs), NIH T,
and keratinocyte (A). No signicant cytoprotection was
observed with both the extracts used in H2O2and xan-
thine oxidase induced damages in cells []. However, the
plant extracts showed signicant protection against oxida-
tive stress in several in vivo models. Treatment with bitter
melon extracts normalized the elevated concentrations of
TBARS, hydroperoxides, and liver markers (ALP, AST, ALT)
in hyperammonemic rats induced by ammonium chloride
while reversing the oxidant-antioxidant imbalance []. is
protective eect is mediated probably by increasing the
 Journal of Lipids
Acetyl CoA Malonyl CoA
Increased biogenesis
Cell membrane
F : Hypothetical mechanism of bitter melon on fat metabolism in liver tissue via AMPK-PPAR𝛾mediated pathways.
activity and concentrations of GPx, SOD, and catalase and
reduced glutathione in the liver and brain tissues []. e
plant extracts also prevented the lipid peroxidation in chronic
sucrose fed rats and normalized the reduced glutathione level
in liver [].
10. Clinical Studies That Used Bitter Melon
Bitter melon extracts are considered the most popular tradi-
tional medication used for the treatment of diabetes despite
studies with bitter melon data with human subjects are
limited and awed by poor study design and low statistical
power []. Table summarized some important clinical
studies that used various parts of bitter melon. Ahmad et
al. reported that the aqueous homogenized suspension of
the vegetable pulp signicantly reduced both fasting and
postprandial serum glucose levels in noninsulin dependent
diabetic patients []. However, this study design was not
a randomized placebo controlled study which lacks the
appropriate comparison and biasness could not be excluded.
Similar study was conducted by Tongia et al., who reported
that  mg capsule of bitter melon twice daily synergistically
improved hypoglycemic action of metformin and gliben-
clamide []. Randomized, double-blind, placebo-controlled
trials with bitter melon are inconclusive and shortfall in
appropriated study design, patient number, and duration of
study. Fuangchan et al. reported a decline of fructosamine
level in diabetic patients at week  with mg/day dose
while other doses tested failed to show any signicant eect
[]. Tsai et al. reported a decreased metabolic syndrome
incidence rate compared to that at baseline and reduction
of waist circumference in studied patients []. Trakoon-
osot et al. also reported an improvement of diabetes con-
dition in patients treated with bitter melon and a decline
of advanced glycation end products (AGEs) in serum aer
 weeks of the intervention were reported []. However,
other investigations reported by Dans et al. showed that
two capsules of bitter melon three times a day aer meals
for  months failed to produce any signicant improvement
in diabetic conditions []. Almost all authors reported no
serious side eects during the study period []. In some
patients, headache, dizziness, stomach pain, and bloating
were also reported.
11. Summary and Future Prospective
To date ,M.charantiahas been extensively studied worldwide
for its medicinal properties to treat a number of diseases
like diabetes, dyslipidemia, obesity, and certain cancers.
Isolated compounds from this plant like charantin, insulin-
like peptide, and alkaloid-like extracts possess hypoglycemic
properties similar to its crude extracts. e plant and fruit
extracts and dierent compounds seem to exert their bene-
cial eects via several mechanisms like AMPK, PPARs, LXRs,
SREBPs, Sirts mediated glucose, and fat metabolism in vari-
ous tissues which are directly related to the benecial eect of
controlling and treating diabetes mellitus, dyslipidemia, and
Journal of Lipids 
obesity related cardiovascular complications. A hypothetical
mechanism has been proposed in Figure which aimed to
explain the lipid lowering eect of bitter melon. However, a
knowledge gap in research was observed in the eld of any
direct eect of this plant on cardiac function, hypertension,
and hypercholesterolemia induced atherosclerosis. Moreover,
clinical studies reported mostly lack appropriate study design
conduct more double blind randomized trials with bitter
melon extracts in diabetes patients as well as in obese
population. Further researches are also advocated for eliciting
the eect of dierent dose of bitter melon in diabetic heart
failure and hypertension both in animal and in patients with
diabetes, obesity, and cardiovascular complications.
ACC: Acetyl-CoA carboxylase
ACE: Angiotensin-converting enzyme
ALP: Alkaline phosphatase
AST: Aspartate transaminase
ALT: Alanine aminotransferase
AMPK: 󸀠AMP-activated protein kinase (󸀠
adenosine monophosphate-activated
protein kinase)
ApoB: Apolipoprotein B
BAT: Brown adipose tissue
BMI: Body mass index
C/EBP: CEBPB CCAAT/enhancer binding
cAMP: Cyclic adenosine monophosphate
(󸀠-󸀠-cyclic adenosine
CPT-I: Carnitine palmitoyltransferase I
CYPA: Cholesterol  alpha-hydroxylase
(cytochrome P A)
DPPH: ,-Diphenyl--picrylhydrazyl
FAS : Fatty acid s y n t h a s e
FFA: Free fatty acid
FGF: Fibroblast growth factor
FGFR: Fibroblast growth factor receptor
GLUT: Glucose transporter type 
HDL: High-density lipoprotein
HDL-C: High-density lipoprotein cholesterol
HF: High fat
HPLC: High-performance liquid
IDDM: Insulin-dependent diabetes mellitus
IGF: Insulin-like growth factor
IL-: Interleukin 
IR: Insulin receptor
IRS-: Insulin receptor substrate 
LDL: Low-density lipoprotein
LDL-C: Low-density lipoprotein cholesterol
LDLR: Low density lipoprotein receptor
L-NAME: L-NG-nitroarginine methyl ester
LXR: Liver X receptors
MCP-: Monocyte chemoattractant protein-
mRNA: Messenger ribonucleic acid
NAFLD: Nonalcoholic fatty liver disease
NEFA: Nonesteried fatty acids
NF-𝜅B: Nuclear factor kappa-light-chain
enhancer of activated B cells
NIDDM: Noninsulin-dependent diabetes mellitus
PEPCK: Phosphoenolpyruvate carboxykinase
PGC: Peroxisome proliferator-activated
receptor gamma coactivator -alpha
PIK: Phosphoinositide -kinase
PKA: Protein kinase A
PPAR: Peroxisome proliferator-activated
RCF: Rat cardiac broblast
Sirt: Sirtuin 
SREBP: Sterol regulatory element-binding
STZ: Streptozotocin
TDM: Type  diabetes mellitus
TAE: Total aqueous extract
TAG: Triacylglyc e r ols
TBARS: iobarbituric acid reactive substances
TC: Total cholesterol
TG: Triglycerides
TNF: Tumor necrosis factor
VLDL: Very low-density lipoprotein
WAT: White adipose tissue
WHO: World Health Organization.
Conflict of Interests
e authors declare that they have no conict of interests.
e authors thank Kumar Bishwajit Sutradhar, Senior
Lecturer, Department of Pharmacy, Stamford University,
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