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Rao and Krishnamurthy Int. J. Pure App. Biosci. 6 (1): 147-158 (2018) ISSN: 2320 – 7051
DOI: http://dx.doi.org/10.18782/2320-7051.6169 ISSN: 2320 – 7051
Int. J. Pure App. Biosci. 6 (1): 147-158 (2018)
Review Article
Herbal Approach for the Management of Obesity – A Review
Sreedevi Prabhakar Rao1 and Vijayalakshmi Krishnamurthy2*
1
Research Scholar, 2Associate Professor,
Department of Biochemistry, Bharathi Women’s College, Chennai, Tamil Nadu
*Corresponding Author E-mail: viji42research@yahoo.co.in
Received: 5.01.2018 | Revised: 3.02.2018 | Accepted: 7.02.2018
ABSTRACT
Obesity is primarily considered to be a disorder of energy balance, and it has recently been
suggested that some forms of obesity are associated with chronic low-grade inflammation. There
are anti-obesity drugs, affecting the fundamental processes of the weight regulation; however
they have shown serious side effects, which outweigh their beneficial effects. Alternatively,
dietary phytochemicals and natural health products offer great potential as an efficient weight
loss strategy by modulating lipid metabolism and/or increasing BMR and thermogenesis.
Specifically, Polyphenols such as Chlorogenic acid, Ferulic acid, Gallic acid, Cinnamaldehyde,
Curcumin, Naringin, Quercetin, Capsaicin and Caffeine have been reported to increase lipolysis
and induce fatty acid β-oxidation through modulation of genes. In this review article, we discuss
selected phytochemicals and medicinal plants in relation to their integrated functionalities and
specific mechanisms for weight loss.
Key words: Obesity, low-grade inflammation, anti-obesity drugs, phytochemicals, medicinal
plants.
INTRODUCTION stress which contribute to obesity. Nicotine
Obesity is a most common metabolic disorder level helps to burn calories; therefore quitting
in the societies, which results from excess fat smoking often leads to reduction in calorie
accumulation in the body. It is not the single burning, thereby causing obesity. Aging
disorder but, a heterogeneous group of process results in muscle relaxation, more
conditions with multiple causes 1. Obesity is particularly for those indulged in sedentary life
accredited to genetic and family link, health of style that ultimately leads to weight gain due
an individual, certain medications, emotional to inhibition of calorie burning. Adequate
factors, age, smoking, pregnancy, lack of sleep sleep is an essential for maintaining a good
etc. Hormone treatment often prescribed for health. Sleep maintains a balance between
hypothyroidism, Cushing‘s syndrome, hormones like ghrelin, leptin that are
Polycystic Ovarian disease may lead to responsible for hunger. Insufficient sleep
overweight. Corticosteroids, antidepressants, disturbs the balance and thereby increases
and seizure medicines also results in weight appetite, consequently leading to excess fat2.
gain, boredom, anger, anxiety and too much of
Cite this article: Rao, S.P. and Krishnamurthy, V., Herbal Approach for the Management of Obesity – A
Review, Int. J. Pure App. Biosci. 6(1): 147-158 (2018). doi: http://dx.doi.org/10.18782/2320-7051.6169
Copyright © Jan.-Feb., 2018; IJPAB 147
Rao and Krishnamurthy Int. J. Pure App. Biosci. 6 (1): 147-158 (2018) ISSN: 2320 – 7051 Excessive day sleepiness (EDS) and tiredness these approaches are too expensive for routine are common symptoms of obesity and are use. linked to an individual‘s health issues3. Metabolism during Obesity: Measurement of Obesity: The two major sources of energy in a human There are many methods that can be used to body are carbohydrates and fatty acids. The evaluate body fat in different populations4,5. body produces energy in the form of ATP by While anthropometric measurements of oxidation of carbohydrates, fats and proteins weight-for-height have been traditionally used through tricarboxylicacid (TCA) cycle; and by to evaluate obesity, more recently, BMI has oxidation of fatty acid through β-oxidation. become a standard parameter. BMI is defined Under normal conditions, more ATPs are as weight in kilograms divided by height in produced through β-oxidation of fatty acids in square meters. The normal range is 19–24.9 the mitochondria than through oxidation of kg/m2, while overweight defined as 25– 29.9 carbohydrates. The first requirement in β- kg/m2, and obesity as ≥30 kg/m2. oxidation of fatty acid is the presence of fatty Unfortunately, BMI does not provide any acyl-CoA and its transport into the insight into regional body fat distribution. mitochondria which is facilitated by CPT- 1 Thus, simple anthropometric measurements, (Carnitine Palmitoyl transferase -1) 8, 9. Acetyl- such as waist circumference, can also be used CoA carboxylase (ACC) plays a central role to determine the valid index of visceral fat both in fatty acid β-oxidation and fatty acid accumulation, in addition to being able to biosynthesis. ACC catalyses the carboxylation serve as an indicator of health risks associated of acetyl-CoA to malonyl-CoA, which can be with visceral obesity. A waist circumference used by fatty acid synthase for fatty acid of greater than 102 cm in men and 88 cm in biosynthesis. As malonyl-CoA is the substrate women is a risk factor for cardiovascular for fatty acid biosynthesis, malonyl-CoA is a disease. A particularly important direct inhibitor of mitochondrial fatty acid anthropometric parameter that has been uptake as well as inhibition of CPT-1 10. increasingly applied in recent years is sagittal Therefore, the enzymes CPT-1 and fatty acid abdominal diameter6. Using a simple caliper synthase (FAS) directly regulate catabolism that was originally developed by Kahn and this and anabolism of fatty acids 11. 5′- Adenosine anthropometric indicator can measure visceral monophosphate-activated protein kinase fat tissue alone 7. With tetra polar bioelectric (AMPK) regulates fatty acid metabolism by impedance analysis, body density can be inhibition of ACC activity 11 and stimulation measured by exposing the body to an alternate of CPT-1 production 12.Thus AMPK stimulate current of 50 kHz at strength of 800 μA which fatty acid β-oxidation and down regulate fatty provides the information on the relationship acid biosynthesis. SIRT1 and SIRT3 belong to between the body mass and volume. Radio the sitrulin family of the silent information isotopic techniques use deuterium or tritium as regulator 2 enzymes which have been found to markers to measure the total body liquid and regulate hepatic lipid metabolism by the total body potassium. Ultrasonography activation of the AMPK pathway thus measures fat tissue and is currently considered facilitating fatty acid oxidation 13. Obesity can to be a favoured technique by which one can lead to impaired cellular metabolism due to measure both subcutaneous and visceral fat dependence on glucose oxidation (for ATP tissues. Measurements are carried out by using production) and decrease in fatty acid a 7.5- and 3.5-mHz transducer for the oxidation, thus leading to more fat deposition subcutaneous and visceral fat tissue, in skeletal muscles, hepatocytes and other respectively. The most accurate method of cells14. measuring central obesity is through the use of Adipokines: magnetic resonance imaging or computer- Fat cells called adipocytes actively secrete a assisted tomographic scanning. Unfortunately, variety of products that create a link between Copyright © Jan.-Feb., 2018; IJPAB 148
Rao and Krishnamurthy Int. J. Pure App. Biosci. 6 (1): 147-158 (2018) ISSN: 2320 – 7051
obesity and other components of metabolic suppresses hepatic glucose production 26.
syndrome. These biologically important Importantly, adiponectin also inhibits NF-κB
substances are called adipocytokines {Leptin, activation, thus, attenuating inflammation 29.
Resistin, Adiponectin, Free fatty acid (FFA), Unlike adiponectin, plasma levels of visfatin
Tumor necrosis factor α (TNF-α), Interleukin - increase in parallel with visceral fat in both
6 (IL-6), Plasminogen activator and inhibitor mice and humans 30 so the role of visfatin in
(PAI), Angiotensinogen, Vistafin and insulin resistance needs additional
15
Glucocorticoids} . Peroxisome proliferator investigation. Taken together, these
activated receptor–γ (PPAR-γ) and observations suggest that the adipocyte is an
CCAAT/enhancing binding proteins (C/EBPα, integral coordinator of the relationship among
C/EBPβ & C/EBPδ) are key transcription obesity, diabetes, and CAD. Infiltration of
factors in adipogenesis. C/EBPβ & C/EBPδ adipose tissue by macrophages and
are induced during the early adipogenesis. lymphocytes has been associated with insulin
Activation of these transcription components resistance. It is believed that these
is then followed by activation of PPAR- γ and inflammatory cells alter adipogenesis via
C/EBPα, the central transcriptional regulators secretion of pro-inflammatory cytokines which
in adipogenesis. Once PPAR- γ and C/EBPα may result in impaired hyperplasia of adipose
are activated, they cooperatively enhance each tissue in response to high caloric intake 31.
other, which then induce further expression of Proinflammatory cytokines like TNF-α and IL-
adipogenic genes required for maintaining 6 are secreted by macrophage infiltrated
adipogenic characteristics and terminal adipose tissue 32. IL-6 promotes insulin
differentiation. In particular, PPAR- γ is a resistance by inducing lipolysis and inhibition
central regulator of adipogenesis and of adiponectin secretion. IL-6 has also been
represents a good target for antiobesity therapy suggested to have role in the early stages of
16, 17
. PPAR- γ coactivator -1α (PGC-1α) is atherosclerosis 33. TNF-α binds to TNF-α
recognised as key regulators of mitochondrial receptor and activates the C-JUN terminal
biogenesis and function through interactions kinase (JNK) and /or Nuclear factor-κB (NF-
with nuclear receptors 18. Severe calorie κB). Increased JNK activity in obesity leads to
restriction 19 and exercise 20 increases PGC-1α fortified insulin resistance as Insulin receptor
expression in skeletal muscle of obese substrate-1 (IRS-1) activity is decreased 34.
subjects. PR domain containing 16 (PRDM TNF-α affects the expression of several
16) is a zinc finger protein that directs the adipokines with central role in mediating the
white adipocyte lineage towards brown fat in health risks associated with obesity like
vivo, by activating a robust pattern of brown decrease in adiponectin levels, increase in
fat gene program and simultaneously leptin, more FFA are released, circulating PAI
suppressing the white fat gene program levels are elevated and more MCP-1
21
.Leptin can alter insulin action and has (Monocyte chemoatrractant protein-1) are
recently been recognized as an important secreted 35. The increased PAI-1 concentration
mediator of obesity-related hypertension 22. in the vessel wall as well as in the plasma
Angiotensinogen, the precursor of angiotenin could participate in increased cardiovascular
II, a key mediator of vascular injury, can be risk and unfavourable plaque formation in type
produced and secreted by adipose tissue 23. In 2 diabetes 36. MCP-1 is elevated in type 2
contrast, excessive visceral adipose tissue has diabetic patients, 37 it is suggested to be
been shown to be associated with decreased involved in regulation of insulin sensitivity in
adiponectin levels 24 an important hormone 3T3-L1 adipocytes in vitro 38. These
25, 26
that exerts antidiabetic and observations suggest that the adipocyte is an
27, 28.
antiatherogenic functions Adiponectin integral coordinator of the relationship among
activates AMP-activated protein kinase, which obesity, diabetes, and CAD.
promotes skeletal muscle glucose uptake and
Copyright © Jan.-Feb., 2018; IJPAB 149Rao and Krishnamurthy Int. J. Pure App. Biosci. 6 (1): 147-158 (2018) ISSN: 2320 – 7051
General approach in management of & pyrimidine of nucleic acids, chlorophyll etc.
obesity: Secondary constituents are the remaining plant
Weight management is a commonly chemicals such as Alkaloids, Terpenes,
recommended approach which is based on Flavonoids, Ligans, Plant Steroids, Saponins,
lifestyle modifications including dieting, Phenolics, and Glucosides 42.
increased physical activity and exercise. Phenolic acid:
However, physical exercise and dieting is Chlorogenic acid: Chlorogenic acid
often a difficult routine to maintain for lifetime significantly lowered body weight, visceral fat
and the results can be disappointing in long mass, and plasma leptin and insulin levels
term. At present, the combination therapy of compared to high fat control group in which
reducing calorie intake, increased energy adiponectin level was elevated in plasma 43
expenditure and pharmacotherapy is becoming and in visceral adipose tissue (VAT) 44.
more popular. To this end, several drugs such Chlorogenic acid increased the protein
as Fenfluramine, R-Fenfluramine, Temin, expressions of PPAR-γ and PPAR-α 44 in liver.
Sibutramine, Orlistat, Qsymia, and Belviq are Chlorogenic treatment attenuated
approved by FDA towards weight inflammation in the liver and white adipose
management aid. However, four of these drugs tissue (WAT) accompanied by a decrease in
were removed later on, due to their adverse mRNA levels of macrophage marker genes
health effects 39. In addition, all current weight that included F4/80, Cd68, Cd11b, Cd11c and
management drugs in the market have high TNF-α 45.
cost as well as potential side effects thus Ferulic acid: Ferulic acid was shown to
causing dissatisfaction to the consumers. improve lipid and glucose homeostasis by
Finally, Gastric surgery has been the most modulating the expression of lipogenesis
effective approach in severely obese to show genes (SREBP1C, FAS, ACC), stimulating β-
long term effects. Despite the progress in oxidation genes (CPT1α, PPAR- α) and
weight management strategy in recent years, gluconeogenesis enzymes, PEPCK (Phospho
obesity still poses a serious challenge to the enol pyruvate carboxy kinase) and G6pase
scientific community 39, 40. Therefore, there is a (Glucose 6 phosphatase) 46. Additionally,
considerable demand to explore natural Ferulic acid regulated hepatic GLUT2 gene
therapies in developing an alternative, safer expression via modulation of transcription
and effective therapy. For this reason, a variety factors have been observed in high fat and
of natural phytochemicals have been explored fructose induced type 2 diabetic adult male
for their ability to increase fatty acid β- rats 47. Furthermore Ferulic acid has
oxidation, fat absorption and suppress appetite contributed to the modulation of inflammatory
control. This review article focuses on those processes via suppression of NO production by
phytochemicals and the medicinal plants that down regulating the expression of NF-kB
potentially increase fatty acid β-oxidation in mediated iNOS gene 48.
relation to weight loss. Gallic acid: Gallic acid improved glucose
Herbal approach in management of obesity: tolerance and lipid metabolism in obesity
Phytochemicals: mice, thereby showing evidence of anti-
Phytochemicals are non-nutritive components hyperglycaemic activity 49, 50, and 51. Gallic acid
present in plant-based diet that exert protective stimulated PPARγ expression and inhibited
or disease-preventing effects. They have been TNF –α and IL-6 expression in treated animals
49, 50
associated with protection from and/or . Gallic acid consumption reduced
treatment of chronic diseases such as heart oxidative stress and GSSG (Oxidised
disease, cancer, hypertension, diabetes and glutathione) content and enhanced the levels of
other medical conditions 41. Phytochemicals reduced glutathione (GSH), GSH peroxidase,
are classified as primary and secondary GSH reductase and GSH-S-transferase in the
constituents. Primary constituents include the hepatic tissue of rats 51.
common sugars, amino acids, proteins, purines
Copyright © Jan.-Feb., 2018; IJPAB 150Rao and Krishnamurthy Int. J. Pure App. Biosci. 6 (1): 147-158 (2018) ISSN: 2320 – 7051
Flavonoids: Naringin: Naringin normalised systolic blood
Cinnamaldehyde: Cinnamaldehyde treatment pressure and improved vascular dysfunction
decreased body weight, fat mass, food intake and ventricular diastolic dysfunction in high
and serum lipid and improved insulin carbohydrate and high fat fed rats. These
sensitivity52, 53, 55. Cinnamaldehyde treatment beneficial effects of naringin may be mediated
significantly decreased the mRNA expression by reduced inflammatory cell infiltration,
of TNF-α 53 that stimulates the AMPK reduced oxidative stress, lowered plasma lipid
activation, PPARα 54, PPARγ, PRDM 16 and concentration and improved mitochondrial
PGC-1α 55 in adipose tissue. Additionally, dysfunction in rats58. Naringin decreased aortic
cinnamaldehyde inhibited the hypertrophy of fatty streak area59 and reduced plaque
adipose tissue and induced browning of white progression60 in high fat diet induced animal
adipose tissue 55. model.
Curcumin: Curcumin inhibited adipocyte Quercetin: Quercetin exerts antiadipogenic
differentiation and promoted antioxidant activity by modulation of ERK and JNK
activities by reducing the expression of TNF- pathways which plays a pivotal role in
α, MCP-1 and PAI-1 and induces the apoptosis of mature adipocytes61. It decreased
expression of adiponectin, the principal anti- the adipose tissue inflammation by enhancing
inflammatory agent secreted by adipocytes 56. the expression of AMPK and SIRT162 and
Thus Curcumin regulated lipid metabolism decreasing the expression the JNK, NF-κB 63.
which plays a central role in the development
of obesity and its complications57.
Table 1: Mechanism of Antiobesity Compounds
Copyright © Jan.-Feb., 2018; IJPAB 151Rao and Krishnamurthy Int. J. Pure App. Biosci. 6 (1): 147-158 (2018) ISSN: 2320 – 7051
Alkaloids: medicinal agent in weight loss process69, 70. In
Capsaicin: Capsaicin increased the expression the screening study of all plants, despite the
of adiponectin, PPARα, PPARγ and different parts chosen, they were extracted
(Uncoupling Protein 2) UCP 2 and decreases using ethanol. This is because alcohol has
the expression of TNF-α and IL-6. UCP 2 does been proven to degrade cell walls and seeds
not mediate adaptive thermogenesis, but they more efficiently than water. The application of
may be significantly thermogenic under more alcohol in the solvent could reduce
specific pharmacological conditions. There is degradation of polyphenols by enzyme
strong evidence that the mild regulated UCP 2 polyphenol oxidase. In addition, all of the
attenuates mitochondrial reactive oxygen identified constituents from plants are either
species production, protects against cellular aromatic or saturated organic compounds so
damage and diminishes insulin secretion 64. the most appropriate method of extraction are
Thus Capsaicin decreased lipid accumulation often obtained through ethanol or methanol
and inflammation in adipose tissue and extraction71. In support of the above
increased insulin sensitivity in animal illustration, a maximum amount of
model65,66. phytochemicals were noted in ethanolic extract
Caffeine: The treatment with caffeine in the of Glycyrrhiza glabra root72, Alternanthera
rats fed with high-carbohydrate, high-fat diet sessilis leaf73 and Punica granatum leaf74.
decreased body fat and systolic blood pressure, Antioxidants protect the human body from
improved glucose tolerance and insulin free radicals and reactive oxygen species.
sensitivity and attenuated cardiovascular and They retard the progress of many chronic
hepatic abnormalities 67. Moreover, Caffeine diseases as well as lipid peroxidation 75. Plant
has increased the serum concentrations of phenolics and flavonoids are effective free
catecholamine and free fatty acids in HFD radical scavengers and their antioxidant
rats. This treatment showed that the intake of activities are well documented76. Natural
caffeine reduced the body fat by lipolysis via antioxidants tend to be safer and are known to
catecholamine68. exhibit a wide range of biological effects such
Antiobesity plants: as antilipase, antibacterial, antiviral, anti-
Medicinal plant samples can be collected from inflammatory, antiallergic, antithrombotic and
the whole plant, or from parts of the plant, vasodilator activities77. Similarly ethanolic
such as the stem, bark, leaf, flowers, and roots. extract of Benincasa hispida fruit78 and citrus
These materials are then processed into paradesi fruit79 possess potent antioxidant
different forms, such as powder or capsules. activity. The extract of Benincasa hispida
However, most of the medicinal plants which fruit80 and Carico papaya leaf contains β-
have shown antiobesity properties were sitosterol 81 which possesses cardio protective
prepared in the form of aqueous or alcoholic effect and thus helps in the management of
extracts. This may be because the decoction, obesity, hyperlipidaemia and atherosclerosis
82
distillation, and infusion procedures that can . The compounds of Garcinia cambogia rind
concentrate the constituents responsible for the like tetra decanoic acid, hexa decanoic acid
therapeutic efficacy of the examined herb. and octa decanoic acid showed better
Some components that inhibit the anti-obesity interaction with Retinol binding protein 4
function of the bioactive compounds can be (RBP4) 83. Another research suggested that n-
isolated by the extraction procedure. hexadecanoic acid, compound from Trigenella
Extraction and partial purification, or the foenum graecum and β- sitosterol, compound
isolation of the active principle(s) could from Carico papaya showed better interaction
increase the bioavailability of the bioactive with fat mass and obesity-associated protein
constituents in medicinal plant extracts and (FTO) 81. Increased serum RBP4 level 84 and
thereby consequently enhance the efficacy of FTO gene variation 85 are observed in obesity.
Copyright © Jan.-Feb., 2018; IJPAB 152Rao and Krishnamurthy Int. J. Pure App. Biosci. 6 (1): 147-158 (2018) ISSN: 2320 – 7051
CONCLUSION AKT / PKB = Protein kinase B.
Obesity is a significant and increasing public GSSG = Oxidised glutathione.
health problem worldwide. Even though, there GSH = Reduced glutathione.
are several treatments, such as surgery and PRDM = Pineal restrictive downstream
drugs, there seems to be no efficient treatment module.
without potential side effects. Natural products PGC-1α = Peroxisome proliferator activated
identified from traditional medicinal plants receptor gamma coactivator – 1 alpha.
have always paved the way for development of MCP-1 = Monocyte chemoatrractant protein –
new types of therapeutics. Most studies 1.
describe phytochemicals in the plant species PAI -1= Plasminogen activator inhibitor – 1.
presenting the great evidence for effective Wnt /β catenin = Wingless typeMMTV
obesity treatment, through both in vitro and in integration site family member / β-catenin.
vivo studies. Experiments are yet to be SIRT1= Silent mating type information
conducted for providing innovative regulation 2 homolog – 1.
technologies aimed at research and UCP2 = Uncoupling protein 2.
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