Roma Ghai1, Sneha Chaudhary1, Kandasamy Nagarajan2, Richa Goel3, Shardendu Kumar Mishra1, Naveen Kumar Tholia4, Nazakat Ali5, Monika Kaurav6*

1Department of Pharmacology, KIET School of Pharmacy, KIET Group of Institutions, Ghaziabad, Uttar Pradesh, India.

2Department of Pharmaceutical Chemistry, KIET School of Pharmacy, KIET Group of Institutions, Ghaziabad, Uttar Pradesh, India.

3Department of Pharmacognosy, KIET School of Pharmacy, KIET Group of Institutions, Ghaziabad, Uttar Pradesh, India.

4Department of Pharmacy and Basic Sciences, Shridhar University, Pilani, Rajasthan, India.

5Dabur Research Foundation, Plot-22, Site-4, Industrial area Sahibabad, Ghaziabad, Uttar Pradesh, India.

6Department of Pharmaceutics, KIET School of Pharmacy, KIET Group of Institutions, Ghaziabad, Uttar Pradesh, India.

Corresponding Author E-mail: monika11kaurav@gmail.com

Article Publishing History
Article Received on : 19 Sep 2023
Article Accepted on :
Article Published : 29 Nov 2023

ABSTRACT:

Obesity is stated to be a notable concern for public health and plays a significant role in the development of numerous non-communicable diseases (NCDs), including conditions affecting the heart, metabolism, and the nervous system. The use of medicinal plants to maintain normal weight and excellent health has been researched for a very long time. However, sufficient empirical data are still lacking to support the scientific notion of the use of herbal products for weight management. Obesity has traditionally been treated with herbal remedies from both domestic and international sources, including Ayurveda (Indian Traditional Medicine System). This article provides a brief overview of obesity-related disorders and their epidemiology, then discusses the potential anti-obesity effects of plants including Salvia plebian, Glycine max, Curcuma longa, Camellia sinensis, Moringa citrifolia, and others using validated tested animal models. It also focuses on the active phytochemical components that give these substances their anti-obesity properties, such as daidzein, ginsenosides, curcuminoids, zingiberene, curcumene, and ellagitannin. The paper was compiled after going through marketed formulations used worldwide, clinical trials and patents based on herbal products for obesity. This review can assist numerous researchers in conducting additional research on exploring the potential.

KEYWORDS:

Anti-Obesity Activity; Adiponectin; Orlistat; Phentermine; Sibutramine; Topiramate

Download this article as:  Copy the following to cite this article:

Ghai R, Chaudhary S, Nagarajan K, Goel R, Mishra S. K, Tholia N. K, Ali N, Kaurav M. An Investigative Study of Medicinal Herbs for Anti-obesity Potential. Orient J Chem 2023;39(6).

Copy the following to cite this URL:

Ghai R, Chaudhary S, Nagarajan K, Goel R, Mishra S. K, Tholia N. K, Ali N, Kaurav M. An Investigative Study of Medicinal Herbs for Anti-obesity Potential. Orient J Chem 2023;39(6). Available from: https://bit.ly/3R2be6v

Introduction

Obesity, a chronic medical condition characterized by excessive or abnormal fat accumulation in the body result in adverse metabolic, biomechanical and psychosocial health consequences. In simple words, it is a disease when a person carries excess body fat that might affect their health. In the world the issue of obesity and overweight is increasing day by day. The person if having obesity or not can be gauged by using a parameter termed “body mass index (BMI). BMI of an individual can be calculated by dividing the weight by square of body’s height expressed as kg/m2. A BMI of 30 or above suggests that a person suffers from obesity 1. Obesity is the major cause of many diseases like diabetes, heart diseases, reproductive diseases, liver diseases, hypertension, and high blood pressure2. According to WHO, the main cause of death is linked to overweight and obesity in the world. In 2016, in world around 11% men and 15% women are obese, which in total is about 13% of the world population. About 41 million of the children under the age of 5 were found obese. India is behind the United State & China among the top 10 countries of obesity patients 3.

Obesity is associated with the consumption of energy-dense foods rich in fat, lipids and by a reduction in physical activity due to increase in urbanization. Studies have noted that in terms of physical inactivity, working in an office environment predisposes to more obesity due to less energy expenditure and more time spent sitting 4. In those pregnant, obesity also predisposes to gestational DM which can cause various adverse effects including prematurity and fetal death 5. Many drugs are available in the market viz orlistat, cetilistat, rimonabant, sibutramine, lorcaserin, metformin, phentermine, bupropion, diethylpropion, dinitrophenol but these drugs cause severe adverse effects like liver damage, heart attack, insomnia, myocardial infarction, nausea, tachycardia, diarrhea, neuropathy, and muscle problem6. The drugs with their side effects are mentioned in table 1.

Table 1: Drug/s with their mechanism of action and side effects

S. No.

Drug/s name

Trade/brand name

Manufacturing company

Mechanism of action

Side effects

1.

Orlistat

Xenical

Roche

Inhibit pancreatic lipase7

Steatorrhea7

2.

Lorcaserin

Belviq

Arena pharmaceuticals

Selective serotonin 2C receptor (5-HT2C) agonist8

Hypoglycemia, headache, dizziness, and constipation 8

3.

Phentermine-Topiramate

Qsymia

Sun Pharmaceuticals Industries Ltd (phentermine),

Ortho-McNeil Pharmaceutical (Topiramate)

Sympathomimetic amine (phentermine) 9, Gamma-aminobutyric acid (GABA) modulator 10

Paresthesia, dizziness, dry mouth, constipation 11

4.

Naltrexone-Bupropion

Contrave

Orexigen Therapeutics, Inc.

Antagonist of the opioid receptor (naltrexone), reuptake inhibitors of dopamine and norepinephrine (bupropion) 12

Vomiting, diarrhoea, constipation, dry mouth, nausea 13

5.

Liraglutide

Saxenda

Novo Nordisk

Glucagon-like peptide-1 receptor (GLP-1) agonist 14

Decreased appetite, dyspepsia, fatigue, nausea, hypoglycemia, dizziness, increased lipase activity14

6.

Sibutramine

Meridia

Abbott laboratories

Sympathomimetic amine 15

Hypertension, serotonin syndrome, dry mouth, insomnia 16

7.

Metformin

Glucophage

Bristol-Myers Squibb

Reduce appetite by attenuating hypothalamic (5′ adenosine monophosphate-activated protein kinase) AMPK activity 17

Lactic acidosis, gastrointestinal upset. 17

8.

Exenatide

Byetta

Amyla pharmaceuticals

Long-acting analogue of hormone GLP-1 18

Severe nausea 18

9.

Pramlintide

Symlin

Amyla pharmaceuticals

Inhibits hepatic gluconeogenesis by inhibiting glucagon synthesis 19

Pain at injection site, hypoglycemia, vomiting, stomach pain and exhaustion. 19

10.

Rimonabant

Acomplia

Sanofi-Aventis

Cannabinoid1 receptor antagonist 20

Severe depression and predisposes to neurons related diseases. 21 ]neuron-related

11.

Phendimetrazine

Adipost

Elite Pharmaceuticals

Sympathetic agonist 22

Interstitial nephritis and cardiac ischemia.22

 

Due to above-fore said side effects of drugs, we selected those plants where validated model studies were known to be conducted. So this review paper focuses on epidemiology aspects of obesity as well as the validated herbs which have been demonstrated scientifically for obesity.

Methodology

The herbal plants chosen were thoroughly researched through a database along with the validated animal models. Different keywords were entered into the search engines like Pubmed, Google Scholar, ScienceDirect to search for the secondary data. Some of the examples are “herbal plants for obesity”, “obesity role in different diseases”, “obesity in children”, “drugs use in obesity treatment”. Animal studies reports were simultaneously being studied for the chosen plants using key words like “pre-clinical” or “non-clinical”.

Obesity and other diseases

Obesity is a chronic condition marked by excessive body fat. Obesity is defined by a body mass index (BMI) which is determined by dividing weight in kg by height in m2 (kg/m2). Persons are classified in three categories on basis of BMI. Underweight or normal weight is 25 kg/m2, followed by overweight (25 to 30 kg/m2), moderate obesity (30 to 35 kg/m2), and severe obesity (BMI 35 kg/m2).23. In recent decades, the prevalence of obesity has risen rapidly in both Western societies and the developing world24. As per previous studies in 2014, the number of obese people in the world increased upto 641 million out of which 266 million are men and 375 million are women as compared to the year 1975 [105 million total adults out of which 34 million are men and 71 million are women]. If this trend continues, worldwide obesity prevalence is anticipated to reach 18% in men and 21% in women by 202525. Overall, obesity is a chronic recurring and increasing disease26 and a prominent possible risk for global fatalities. Furthermore, significant weight increase tendencies have been recorded for children and adolescents, weakening the present and future health status of the community 27-30. The World Health Organization (WHO) labelled obesity a global epidemic to emphasize the threat to public health, yet it remains an under-recognized public health problem in many areas 23,31,32.

Obesity, depending on the degree and length of weight gain, can induce and/or exacerbate a wide range of co-morbidities, including type 2 diabetes mellitus (T2DM), cardiovascular disease, some types of cancer, and cognitive issues, among others. (Figure 1).

Epidemiology of obesity

Obesity and Diabetes mellitus

The risk of having type II diabetes due to excess weight rises by a factor of 3 and obesity by a factor of 7 relative to average weight. Childhood and adolescence overweight and weight gain through early to middle-aged age are high-risk factors for diabetes 33. Obesity itself increases the possibility of diabetes even in the absence of other metabolic disorders 34.

Obesity & cardiovascular diseases

Excess body weight is an accepted possibility for heart disease and ischemic stroke, along with the common history of dyslipidemia and hypertension 35. Due to obesity, metabolic fat associated with visceral obesity is thought to play a major role in the process of cardiovascular disease. Several studies have revealed a decrease in life expectancy among fat people. The primary cause of excess mortality in obesity was usually found to be a cardiovascular disease as compared to normal weight36.

General obesity and fat distribution were related to increase incidence of elevated blood pressure in a study. Obesity usually reveals much about the level of blood pressure relative to the distribution of weight. In the prospective study, the baseline BMI and the subscapular folding thickness of the skin were reported to be independent of the hypertension predictors, with an average total odds ratio of 3.85 and 3.75 for the top vs. the lowest quintile, respectively 37

Obesity and Cancer

As per US cancer risk statistics data around the world 4.7 % men (every 37,670 new cases) and 9.6% women (every 74,690 new cases) have arisen due to obesity 38. Diabetes being a significant risk factor for obesity, which is already a potential risk for most cancers, it has been known that obesity is associated with an increased risk of, postmenopausal, endometrial esophageal, colon, pancreatic and renal cancer 39. A meta-analysis study found that the risk of gallbladder cancer among those overweight and obese was 15 per cent and 66 per cent higher than those of average weight, respectively. In women, the correlation between obesity and gallbladder cancer was greater than in men40. Excess body weight can be a risk factor for leukaemia according to cohort meta-analysis. Findings demonstrate that overweight and obese individuals are 14 per cent and 39 per cent higher than non-overweight individuals, respectively. Obesity was directly associated with both female and male leukaemia and all subtypes of leukaemia. Obesity has also been linked with a high risk of leukaemia mortality41.

In retrospective study, the chances of patients with severe obese trauma were at least 30 per cent more likely to die and about twice as likely to have serious problems compared to non-obese patients. Several obese patients have a two-to four-fold higher risk of acute renal failure, a double higher risk of sepsis, and an elevated risk of bedsore up to eight-fold42. Patients with obesity have impaired respiratory physiology associated with decreased lung volume and hypoxaemic compliance, due to a limited ability to compensate this impact will be exacerbated by trauma. Patients with obesity have chances of more chest injuries, including rib fractures and contusions 43. The implications of an epidemic of worldwide obesity may not only be a greater burden on obese chronic and infectious diseases, but it is also a higher risk of infectious diseases due to obesity44.

Obesity and mental health

Elderly people with higher adiposity are at higher risk of brain atrophy and therefore dementia. Elderly participants were affected by obese-associated brain atrophy and confirmed to be clinically unstable for at least five years after baseline testing. The findings suggest that individuals may have greater brain atrophy due to obesity or factors influencing obesity and this atrophy may, in effect, predispose them to potential cognitive impairment and dementia46. Obesity has been associated with a lesser proportion of gray matter orbital cortex, including reduced efficiency in some regions of executive function in children and adolescents (aged 9 years)46. The risk of Alzheimer’s disease raises mid-life overweight, vascular dementia or any degenerative disease by 35 per cent, 33 per cent and 26 per cent respectively; and increased risk of obesity reported47.

Medicinal plants with anti-obesity activity

Over the years, several drugs were used to treat obesity, but most of them have now been taken off due to dangerous side effects48. Orlistat is the only FDA-approved long-term obesity treatment. Steatorrhea is a digestive side effect of this medication. Sibutramine, another anti-obesity medicine, was discontinued globally due to increased significant, non-fatal cardiovascular events. Pharmacotherapy failures highlight the need for further obesity treatments49,50.

Natural products are widely used in healthcare and as dietary supplements 51. Dietary phytochemicals have recently sparked significant interest as possible therapeutic agents for health promotion and alleviation of obesity and related diseases52. Plant products have long been a fruitful source for the discovery of new medications, and these are used in the most prevalent naturopathy systems due to their chemical richness and aptitude to work on numerous biological targets53. A diverse range of medicinal plants and their active constituents can produce beneficial anti-obesity effects such as Curcuminoids (Curcumin), Lignans (Podophyllotoxin), flavones (Apigenin, Luteolin), phenolic acids (o-Coumaric acid, chlorogenic acid), flavanols (Quercetin), phytosterols (Diosgenin, Brassicasterol, β-sitosterol), alkaloids (Caffeine), Resins (Capsaicin), Pigments (Malvidin, Pelargonidin) 54.

Few of the most famous traditional medicinal plants for the treatment/ prevention of obesity as well as substitutes to synthetic drugs in obese models are discussed below and in table 2 and depicted in figure 2.

Curcuma longa L. (f. Zingiberaceae) is also known as turmeric which is used as a spice mainly. It is used traditionally as Ayurvedic, Unani and Homeopathic medicine [55]. It is the plant which works against many diseases like cancer, neurological, autoimmune, cardiovascular, metabolic disorders, lung, and liver diseases. Curcuma longa contains carbohydrates, fat, minerals, and moisture also in different proportions 56.

Carbohydrate consumption is related to weight gain57. By elevating the adipose tissue expression of GLUT4 (Glucose transport type 4) the uptake of glucose increases. It is described that down-regulation and overexpression of GLUT4 elevate the sensitivity and glucose intolerance58. Curcumin by the phosphoinositide phospholipase C- phosphoinositide 3-kinase (PLC-PI3K) pathway enhances the expressions of GLUT4 through glucose uptake by skeletal muscle. Thus it helps in the management of obesity by elevating calories consumption by improving glucose utilization59.

Panax ginseng C. A. Mey (f. Araliaceae) The root of P. ginseng is mainly used for treatment of different diseases like nervous disorders, anemia, overfatigue, lack of sexual desire, heart pain, nausea, shortness of breath, tuberculosis, diabetes, amnesia, and disorder of liver, kidney and heart60. It mainly contains vitamins, proteins, carbohydrates, niacin, calcium, iron and phosphorus 61. The main active constituents of P. ginseng are saponins and polysaccharide.

The possible mechanism for lowering of reactive oxygen species (ROS) and lipid accumulation production is via the initiation of CCAAT/enhancer-binding protein-homologous protein10 (C/EBP), as it diminishes fat accumulation and down regulates the protein level of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 62. Lin. et al. found that when panaxoside Rb1 was given by intraperitoneal injection for 3 weeks in diet-induced obese mice, its body weight, food consumption and blood lipid profile decreased63.

Tecomella undulata (f. Bignoniaceae) This is found in the north-west and western parts of India, as well as in the outer Himalayas. It is usually referred to as Rohitaka. It is used in the treatment of leucoderma, spleen, syphilis, spleen, skin disease, and liver disease64. It mainly contains alkanes, alkanols and β-sitosterols and undulatosides A & B, tecomelloside and tecoside (iridoid glucosides) 65.

Alvala, R. et al. established that a dose-dependent decrease in cellular triglyceride is caused by consumption of T. undulata. Targets of sirtuin 1 (SIRT1) like peroxisome proliferator-activated receptor-gamma (PPAR-γ) and C/EBPα which are the master regulators of adipogenesis are also reduced. The level of leptin fatty acid synthase (FAS), lipoprotein lipase (LPL), E2F1 and protein are also decreased. While the level of adiponectin is increased. T. undulata also inhibits lipogenesis by the activation of SIRT1 66.

Salvia plebeia (f. Lamiaceae) The genus Salvia includes more than 1000 distinct types of crops that grow extensively in hotter and tepid areas. There’re around 100 species of Salvia in China, many of which are found in the southwest67. Steroids, phenolic acids, terpenoids and flavonoids were revealed to be the main constituents of this genus, showing comprehensive biological activities including antioxidant, antimicrobial, anti-HIV and cytotoxic activity68.

In a study on mice Choi, SI et al reported that Salvia plebeia extract (SPE) therapy reduced serum, body weight, and fat accumulation levels in the tissues. SPE therapy also led in mRNA transcriptional changes in genes linked to obesity in liver tissue, epididymal adipose tissue (AT), and subcutaneous AT. In the SPE-treated group of liver and fat tissues, transcriptions of C/EBPα mRNA and PPARγ were inhibited significantly. Additionally, mRNA transcription of αP2, LPL, FAS, sterol regulatory element-binding protein (SREBP-1c)and hormone-sensitive lipase(HSL) genes were suppressed by SPE therapy. PPARγ is distributed mainly in ATs, where it controls the development of fat in cells69.

Glycine max (f. Fabaceae) is commonly known as soybean. Soybean is indigenous to East Asia, primarily China, Korea and Japan, and later began to be cultivated in Europe, America and all across the world 70. Dry soybean comprises 36 per cent protein, 19 per cent fat, 35 per cent carbohydrate (17 per cent of which are dietary fibres), 5 per cent minerals and many other ingredients, including vitamins, isoflavones and saponins 71,72. According to their respective types of aglycon soy saponins are divided into three groups, soyasapogenol A, B and E. The component of saponin A and AB protects the damaged liver from oxidation and increases lipid metabolism 73.

Daidzein (Dzd) is also a chemical constituent of Glycine max which is found to have anti-obesity activity. Dzd therapies considerably decreased plasma total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and free fatty acids (FFA). Naaz. et al, also reported a slight reduction in high-density plasma lipid-cholesterol (HDL-C) levels in mice model. These findings suggest that the rise in TC by eating a high-lipid diet is due to an increase in LDL-C concentrations. As a result, the effect of Dzd was primarily expressed in the reduction of LDL-C. Dzd increased lipolysis by activating the hormone-sensitive lipase 74.

Camellia sinensis (f. Theaceae) is commonly known as Green Tea in which two different types of tea exist in the south and south-east Asia, including Malaysia and Australia. C. sinensis.var. sinensis iswidely grown in China, Japan, and Taiwan, while in the south and south-east of Asia, Australia, and other regions of China, C. sinensis var. assamica (Assam tea) is in the majority in the south and southeast Asia, including Malaysia 75. Important compounds of leaf buds and very young leaves are amino acids, carbohydrates, polyphenols, proteins, chlorophyll, volatile organic compounds, fluoride, alkaloids, aluminium, minerals and trace elements 76,77. Many evidence have shown that green tea seems to have an anti-proliferation effect on hepatoma cells and hypolipidemic activity in hepatoma treated rats, as well as hepatoxicity and post-initiation preventive measures for mammalian cancer 78,79. Green tea catechins may also serve as anti-tumour agents 80.

In the regulation of lipolysis and energy consumption, sympathetic nervous system (SNS) performs a vital role. Some substances that induce or delay the production of norepinephrine (NE), a significant mediator of SNS activity, can induce energy usage and promote fat oxidation. Caffeine, found naturally in green tea, also affects SNS effect by reducing phosphodiesterase, an enzyme that rapidly degrades intracellular cyclic adenosine monophosphate (cAMP) as a signal provided by NE reactions. It is possible that when taken together, green tea catechins (GTCs) and caffeine function synergistically, resulting in major effects on the SNS and thus on energy consumption and lipolysis. Another possible mechanism through which GTCs cause anti-obesity effects may be linked to improvements in fatty acid oxidation and metabolism because of NE and SNS. They facilitate lipolysis in peripheral tissues, further release the free fatty acids into circulation and increase lipid metabolism. It has also been observed that C. sinensis inhibits catechol-o-methyltransferase (COMT) and phosphodiesterase, which further potentially induce lipid oxidation81.

Rubus coreanus Miquel (f. Rosaceae) is a deciduous tree with broad-leaf found in China and Korea. The fruits are frequently referred to as bokbunja in South and North Korea. It is found to constitute multiple bioactive phenolic compounds such as tannins, quercetin, flavonoids, anthocyanins, minerals, vitamins, etc. The unripe fruit is used in traditional Korean herbal medicine for the treatment of diseases like diabetes, asthma, enuresis, and allergy-related diseases 82,83.

The ripe fruits of plant have elevated anthocyanin content. The color of the plant is darker than most other berries. They possess high-quality phenolic compounds like protocatechuic acid, ellagic acid, gallic acid, H-4 blood, H-6 blood, 23-hydroxytormentic acid, and nigaichgoside 84. The effects which were reported are anti-bacterial, anti-fatigue, anti-cancer, antihemolytic, anti-oxidant and anti-inflammatory 85-90.

The unripe Rubus coreanus Miquel (uRCB) butanol fraction and its five active chemical constituents (erycibelline, 4-hydroxycoumarin5-hydroxy2-pyridinemethanol, m-hydroxyphenylglycine and ellagic acid) have been found to prevent adipocyte heterogeneity by suppressing transcriptional factors, including PPARγ, C / EBP and SREBP-1c, adipogenesis-related genes (acetyl-CoA carboxylase) and enzymes (fatty acid synthase). In fact, uRCB decreased body weight, fatty tissue weight (epididymal and persistent fat pad) and serum TC / TG (Triglyceride), glucose and LDL-C levels in high fat-induced (HFD) obese mice 91.

Morinda citrifolia Linn. (f. Rubiaceae) a small tree or shrub native to southern Asia, which grows in the tropic areas and it, is also known as noni 92. Many secondary metabolites are found in the different parts of the plant. They include glycosides like iridoid and triterpenoids, ursolic acid, ketones, lignans, nucleoside, sterols which are the most important components of the fruit, and several anthraquinones which accumulate primarily in the roots, but which are also found in fruit in trace amounts 93.

Morinda citrifolia Linn. (f. Rubiaceae) fruit extracts have shown in-vitro potential for anti-obesity effects. M. citrifolia leaf extract (MLE) modulates adipocytic process by means of leptin like activity to demonstrate anti-obesity characteristics 94. M. citrifolia specifically, by inhibiting LPL activity may help change TG metabolism. This may be caused due to synergistic impacts of catechin with the other phytochemicals present in the MLE and M. citrifolia fruit extract (MFE) 95. This is endorsed by literature reporting that several flavonoids had stronger synergistic impacts than that demonstrated by a single flavonoid 96.

Zingiber officinale (f. Zingiberaceae) is known as ginger commonly, is native of Asia but is now cultivated in West India, Africa, India and other tropical areas. For ginger preparations, the underground stem (rhizome) can be obtained for white-brown colours, depending on how the surface is scrapped and how it is originally handled. This rhizome can be turned into a paste, drink, volatile oil and milk 97. Ayurvedic Pharmacopoeia of India advocates use of dried rhizomes for dyspepsia, decreased appetite, rheumatism, tympanitis, anaemia, coughing and dyspnoea, fresh rhizomes for stomach problems, colic, oedema and mouth infections. It is often used as a postoperative antiemetic, for prevention of motion sickness, anorexia, pregnancy vomiting and bronchitis. It contains alkaloids, flavonoids, glycosides, saponins, terpenoids, tannins, polyphenols (gingerenone A) and phlobotanins, although steroids are not present 98.

The oral supplementation of ginger has significantly prevented and improved obesity from HFD triggered energy metabolism restoration, and increased gene-and protein-related browning, both in white and brown adipose tissue. Furthermore, ginger may control the cycle pathway of glycolysis/gluconeogenesis- Tricarboxylic acid cycle (TCA) and stimulate the SIRT1/AMPK/PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) pathway 99. In another study, with ginger consumption the level of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum and macrophage infiltrations in the epididymal white adipose tissue (eWAT) and liver of the HFD-G decreased substantially. Additionally, the addition of ginger has shown positive impacts on enhanced insulin sensitivity, insulin resistance and glucose tolerance 100. By decreasing hypertrophy and inhibiting macrophage infiltration, gingerenone-A suppressed the growth of obesity and adipose tissue inflammation. This information collectively supports the use of gingerenone A in obesity prevention and its problems 101.

Murraya koenigii (f. Rutaceae) It is an aromatic shrub, more or less a tree up to 6 meters, reaching up to 1,500 m height in India. It is cultivated for its leaves. Plants grow best in sunny to semi-shaded sites in tropical and subtropical climates 102. The main chemical constituents are carbazole alkaloids, coumarin glucoside and scopolin. Curry leaves decrease the amount of blood glucose significantly in diabetic patient’s diet 103.

In a study, the fruit juice of M. koenigii reduced body weight as noted in medium and high dosages groups, due to loss of subcutaneous fats and blood glucose levels 104. In another study, M. koenigii leaves extract-treated HFD rats lead to a time-dependent decrease in bodyweight and cholesterol, TG, reflecting anti-obesity and hypoglycemic activity in M. koenigii. The plant can be used as insulin-sensitive measures to achieve anti-diabetic and anti-obesity effects 105.

Table 2 illustrates some important natural anti-obesity agents and their details such as their biological source, part used and parameters checked during their biological evaluation.

Table 2: Herbs with their Chemical Constituents, Extract, and Animal Models for Treatment of Obesity.

Plant name

Common Name

Family

Plant part used

Chemical constituent

Model used

Parameters checked

References

Curcuma longa

Turmeric

Zingiberaceae

Rhizomes

Carbohydrates, protein, curcuminoides, fat, essential oils

HFD induced obese mice

Insulin, adiponectin in plasma, leptin level, serum TG and cholesterol levels

106,107,108

Panax ginseng

Korean ginseng

Araliaceae

Whole plant

Ginsenosides, alkaloids, glucosides, glucosides, phenolic acid, saponins and polysaccharides.

Male leptin-deficient (B6.VLepob, ‘ob/ob’) mice

Bodyweight, food intake, blood glucose, tissue PPAR-γ and LPL mRNA expression, and tissue GLUT4 and IR mRNA expression

109,110

Tecomella undulata

Rohida

Bignoniaceae

Bark

Iridoid glucoside, naphthoquinone, phytosterols, fatty alcohol, flavonoid glycoside, flavonol, fatty acid and triterpenoids

HFD induced obese mice

LDL, HDL, Cholesterol, TG, VLDL

66

Salvia plebeian

Sage weed

Lamiaceae

Leaves

Flavonoids, monoterpenoids, sesquiterpenoids, diterpenoids, triterpenes, volatile oil and phenolic acids.

HFD induced obese mice

Leptin, adiponectin, glucose, alanine aminotransferase, aspartate aminotransferase, TG, total count, HDL-C, VLDL-C

69,112

Glycine max

Soybean

Fabaceae

Seeds

Isoflavones, lignans, & coumestans. Major bioactive isoflavones are genistein & daidzein

ICR mice

Plasma total count, LDL-C, HDL-C, FFA

 

74,113-114

Camellia sinensis

Tea plant

Theaceae

Leaves

Polyphenols, alkaloids and caffeine, Catechins

Diet rich in fat-induced zebrafish

Bodyweight, body fat volume, fatty acid oxidation activity enzyme activity

115-118

Rubus coreanus Miquel

Korean blackberry

Rosaceae

Fruit

Phenolic acids, triterpenosides, flavonoids, and ellagitannin

HFD induced obese mice

Bodyweight, fatty tissue weight, serum total count/triglyceride, glucose, LDL-C

119-120

Morinda citrifolia Linn.

Indian mulberry

Rubiaceae

Leaves

Iridoid glycosides, Fatty acid, Flavonol glycosides, sterol derivatives and volatile oil

HFD induced obese rats

Bodyweight, BMI, body fat, VLDL & HDL

121,122

Zingiber officinale

Ginger

Zingiberaceae

Dried rhizomes

β-sesquiphellandrene, β-bisabolene, ar-curcumene, α-zingiberene, gingerols, shogaols & ketone derivative

HFD induced obese

Serum level of triacylglycerol & total count, liver lipids, TG levels, alanine aminotransferase, aspartate aminotransferase, HDL-C, LDL-C

123,124

Murraya koenigii

Curry leaf tree

Rutaceae

Leaves

Carbazole alkaloids, coumarin glycosides, scopoline, limonene, and linalool

HFD rats

Total cholesterol, TG, glycemia, bodyweight

125,126

Acacia meansii

Black Wattle

Mimosaceae

Bark

Polyphenols-catechins

HFD induced obese mice

Body weight, insulin levels, adiponectin levels

127

Triticum aestivum

Wheat

Poaceae

Sprout

Glycolipids, alkaloids, carbohydrates, saponins,

proteins, flavonoids

HFD induced obese mice

Serum Cholesterol, body weight, LDL

128

Salix matsudana

Chinese Willow

Salicaceae

Leaves

Apigenin-7-o-D-glucoside

HFD induced obese mice

TG, total cholesterol

129

Acanthopanx senticosus

–

Araliaceae

Whole plant

Carnitine, Chiisanoside, Saponins-lupane type triterpene triglycosides

HFD induced obese mice

LDL-Cholesterol, TG

130

Alipinia officinarum

Galangal

Zingiberaceae

Rhizome

3-methylethergalangin, 5-hydroxy-7-(4’-hydroxy-3’-methoxyphenyl_-1-phenyl-3-heptanone

HFD induced obese mice

Pancreatic lipase, TG

131

Nelumbo nucifera

Lotus

Nymphaeceae

Leaves

Phenolic compounds, Flavonoids

HFD induced obese mice

Total cholesterol, TG, LDL

132

Salacia reticulata

Saptarangi

Celastraceae

Roots and stem

Mangiferin, (-)-epicatechin, (-)-epigallocatechin

HFD induced obese mice

Body weight, fact accumulation

133

Rhizoma coptidis

Huang Lian

Ranunculaceae

Dried powder

Berberine

HFD induced obese mice

Adipose weight, lipid levels, blood glucose levels

134

Citrus depressa

Shiikuwasa

Rutaceae

Fruits

Flavonoids

HFD induced obese mice

Body weight, TG, leptin levels

135

Rosmarinus officinalis

Rosemary

Lamiaceae

Leaves

Carnosic acid, carnosol

HFD induced obese mice

Body weight, TG, Cholesterol, Insulin, pancreatic lipase

136

Cudrania tricuspidata

Cudrang

Moraceae

Leaves

Anthocyanins, polyphenolic pigments

HFD induced obese mice

Body weight, TG

137

Morus austrais poir

Mulberry

Moraceae

Fruits and leaves

Rutin, resveratrol, anthocyanin and deoxynojirimycin

HFD induced obese mice

Body weight, blood glucose levels, TG, total cholesterol

138

Agave angustifolia

Narrow-leaf century plant

Asparagaceae

Leaves

Agavins, Fructan

HFD induced obese mice

Body weight, TG, GLP-1 levels

139

Coffee arabica

Coffee

Rubiaceae

Beans (seeds)

Alkaloids-Caffeine, polyphenols

HFD induced obese mice

Leptin level, IL-6 and TNF-α expression

140

Gymnema sylvestre

Gurmar

Apocynaceae

Leaves

Deacetyl gymnemic acid, catechins, polyphenols, flavonoids (theaflavin and thearubigins)

HFD induced obese mice

Body weight, Total cholesterol, TG, LDL, VLDL

141

Euginea caryophyllum

Clove

Myrtaceae

Flower bud

Eugenol, acetyl eugenol, caryophyllene, humulene

HFD induced obese mice

Body weight, Lipid levels, TG, LDL-C Level

142

 

Ayurvedic formulations with their composition available in market

The market’s anti-obesity products contain food ingredients, herbal compounds, and other functional supplements. The functional supplement market’s most popular segment is food-based supplements. Customers prefer products manufactured from fruits (citrus, melons and berries), grains (brown rice, fermented wheat, soybean), vegetables (celery, radish, leafy greens), or drinking liquids (tea leaves). Traditional Chinese medicine uses herbal combinations including turmeric (Curcuma longa) and mulberry leaf to cure obesity (Morus alba). Asian and Western herbal medicines are common. Herbal remedies may be effective anti-obesity treatments. Probiotics and calcium supplementation are also anti-obesity. Novel anti-obesity treatments must include citrus fruits. Citrus peels and pulp contain triterpenoids, flavonoids, and alkaloids. Citrus fruit extracts lower body weight and white adipocytes weight in cell and animal tests 143. Citrus fruit consumption decreased leptin, an important hormone produced by adipocytes which controls appetite and energy expenditure. This hormonal change is needed for citrus-based anti-obesity treatment. Methoxylated phenolic acids and flavanone glycosides in citrus fruits may impact plasma leptin levels. Green tea based anti-obesity products are also prominent in functional food. Up to 35% of green tea’s dry weight includes polyphenols, which include flavanols, flavones, and flavan-3-ols. Catechins (270 to 1200 mg/day) have been demonstrated to reduce body weight, leptin levels, and fatty acid absorption in clinical trials. Tea, other medicinal components component of tea leaves, affects visceral nervous system activity and promotes energy intake and fat burning synergistically with catechins 144. Here in the below mentioned table few marketed antiobesity products with their constitutional composition mentioned.

Table 3: Ayurvedic formulations with their composition available in market

S. No.

Name of formulation

Composition of formulation

1.

Normact Tablet

Arjuna (Terminalia arjuna), Upakunchika (Nigella sativa), Lasuna (Allium sativum), Sigru (Moringa oleifera), Draksha (Vitis vinifera), Sarpagandha (Rauwolfia serpentina), Gandira (Coleus Sp.),

2.

DhootapapeshwarKanchanar guggul

Kanchanar Twak (Bauhinia variegate), Pippali (Piper longum), Haritaki (Terminalia chebula), Amalaki (Phyllanthus emblica), Shunthi (Zingiber officinale), Varun Twak (Crataeva nurvula.Linn.), Tamalpatra (Cinnamomum tamala), Dalchini (Cinnamomum verum), Maricha (Piper nigrum), Ela (Elettaria cardamomum), Bibhitak (Terminalia bellirica), Triphala Vishesh and Shodhit Guggul (Commiphora wightii).

3.

Mustharishtam

Nut grass (Cyperus Rotundus), gur (jaggery), Dhataki Flower (Woodfordia Fruticosa), Carom Seeds (Trachyspermum Ammi), ginger rhizome (Zingiber Officinale), black pepper (Piper Nigrum), clove (Syzygium Aromaticum), fenugreek (Trigonella Foenum), chitrakmool ( Plumbago Zeylanica), cumin seeds (Cuminum Cyminum)  

4.

Obloz capsules

Guggulu (commiphora mukul), vrikshamla (garcinia gummi-gutta), lashuna (allium sativum), chitraka (plumbago zeylanica)

5.

Medohar gugglu

Black pepper (Piper nigrum), ginger (zingiber officinale), pipali (long pepper), mustak (nut grass),chitrakmool (plumbago zeylanica), haritaki (terminalia chebula), vibhitaki (terminalia bellirica), amla (emblica officinalis), vaividang (embelia ribes), castor oil (errand tel)

6.

Vyodhari gugglu

Ginger (zingiber officinale), agni (plumbago zeylanica), haritaki (terminalia chebula), pepper (piper nigrum), gugglu (cammiphora mukul), pipali (long pepper), musta (Cyprus rotundus), vidanga (embelia ribes), vibhitaki (terminalia bellirica), amla (emblica officinalis)

7.

Navaka gugglu

Ginger (zingiber officinale), pepper (piper nigrum), pipali (long pepper), vibhitaki (terminalia bellirica), amla (emblica officinalis), agni (plumbago zeylanica), musta (Cyprus rotundus), haritaki (terminalia chebula), vidanga (embelia ribes), gugglu (cammiphora mukul)

8.

Garcinia Combogia extracts tablets

Garcinia cambogia (Garcinia gummi-gutta), Green coffee bean (coffea arabica), Green tea (Camellia sinensis), Capsicum (Capsicum annuum)

9.

Green tea and Garcinia Combogia capsules

Garcinia Combogia HCA (Garcinia gummi-gutta), Green coffee bean CGA (coffea arabica), Black pepper (piper nigrum).

10.

Triphala churna

Vibhitaki (terminalia bellirica), Haritaki (terminalia chebula), amla (emblica officinalis).

Clinical trials and Patents on herbal formulation for obesity treatment

Apart from the above said herbal formulations, medicinal herbs have been used in different other ways for treatment of obesity. Many plant species, probiotic microorganisms, and their combinations have been described as potential anti-obesity medications. These have many mechanisms to fight fat. Lipase enzyme inhibitors, adipogenesis modulators and adipogenic factors, appetite suppressors, and miscellaneous are the principal modes of action of these antiobesity drugs 145.

Arvind Kumar in 2009 has reported that dyeing of vastra with the specific medicinal herbs for specific dosha (vata, pitta, kapha) is presented in Ayurveda. When vastra exposed to skin, the herbs absorbed into the body through vastra and this works as a means of providing Ayurvedic treatment for a variety of disorder and diseases including obesity, which was confirmed with experimental research on medicinal plant pigment dyeing of organic natural fibres146. Kim and Su in 2005 have made a composition of weight loss regimen termed chegameuiintang for the treatment of obesity, which comprises varied % weights of mixture of Rehmanniae Radix preparata, Coixlacryma-jobi var. ma-yuen, Stephania tetrandra, Glycyrrhiza glabra, Akebia quinata, Polyporus umbellatus, Alisma canaliculatum, kaphanus sativus, Morus alba, Angelica gigasnakai, Lycium chinese miller, Cornus officinalis, Cnidium officinale, Carthamus tinctorius, Sinapis alba and Sisyrin chium angustifolium. It was found that the regime combined with low calorie diet contributed to reduction in the total fat mass 147

Chung and Ju in 2008 has identified an inexpensive and safe composition comprising medicinal herbs for treating abdominal obesity and constipation, which comprises varied % weights of mixture of adlay, Atractylodis rhizoma, Aloe arborescens, Rheum palmatum, honey and propolis148. Kim and Yeong in 2003 has made an extract of medicinal herbs for obesity treatment and for diet, which comprises varied % weights of mixture of ginseng, Astragalus membranaceus, Imperata cylindrical, Pinellia ternate, Semen coicis, Ganoderm lucidum, Poria cocos, lotus leaves, Lonicera japonica with purified water149.  Cheong and Hee in 2013 has made an excellent therapeutic composition to prevent and treat obesity, which comprises varied % weights of crude drug mixture of Ephedrae herb, Pinellae tuber, Rhei rhizome, Sinomenii caulis rhizoma, Gypsum natriisulfas, Persicae semen, Ponciri fructus, Magnoliae cortex, Poria cocos, Atracylodis rhizoma, Zingiberis rhizome, Grdeniae fructus, Forsythiae fructus, Arctium lappa, Glycyrrhiza radix, Scutellariae radix, mehthae herba, Schizonepeta tenuifolia and Aurantii nobilis pericarpium 150. Other patents related to effect of medicinal plants and herbs in obesity treatment discussed in table 4.

Table 4: Herbs/herbal combination-based patents for obesity treatment.

S No.

Year of Patent

Patent No.

Inventor/Applicant Details

Details

References

ENZYME INHIBITION FOR ANTI-OBESITY ACTIVITY

1.

2010

United States patent (US7816342B2)

Bailly et al.

A formulation consisting of both orlistat and glucomannan, specifically derived from konjac flour, was developed to mitigate the adverse effects linked to orlistat usage, such as occurrences like oily spotting, stools with excess fat content, urgent bowel movements, increased frequency of defecation, and loss of control over bowel movements. The formulation contained a range of 0.1% to 10% of orlistat’s weight and 20% to 75% of glucomannan’s weight. Glucomannan powder, a polysaccharide from of Amorphophallus konjac cultivated in Japan. Lipase inhibitor-orlistat and konjacflour were individually given orally with a 2-hour interval, and this process was repeated 2 to 3 times a day.

151

2.

2010

Japanese patent JP2010265182A

Ikemoto A, Sakamoto K,

Lipase inhibition derived from the outer layer of plants belonging to the Lardizabalaceae family. This botanical family encompasses A. quinata, A. trifoliata, A. pentaphylla, S. mube.

152

3.

2013

Japanese patent (JP5309292B2)

Kamada et al

A mixture with the capacity to hinder lipase activity was formulated using a blend of P. cuspidatum, P. vulgaris, C. pulcherrima, S. samarangense, F. microcarpa, A. zerumbet, H. littoralis, K. pinnata, B. balsamifera, N. domestica, C. tinctorius, C. glauca, T. catappa, and P. luchuensis. These combinations exhibited a range of lipase inhibition percentages, spanning from 48.63% to 98.18%.

153

4.

2013

US patent (US8420131B2)

Smith et al.

In the work by CA Smith, reference was made to pharmaceutical formulations containing extracts from R. rosea and L. speciosa, combined with apple polyphenols, Gardenia fructus. These formulations were explored for their potential in inhibiting α-glucosidase and lipase activities. The findings suggested that the supplements given to the participants had the potential to lead to decreases in weight, blood cholesterol levels, and blood glucose levels.

154

5.

2012

United States patent (US9504725B2)

Kim et al.

A formula for addressing obesity through both curative and preventive approaches employs the butanol and ethyl acetate fractions derived from the rhizomes of P. cuspidatum. This formulation includes an active ingredient, which is the P. cuspidatum extract fraction, constituting 0.1–99.9% of the total weight, alongside suitable pharmaceutical vehicle, excipients, like starch, CaCO3, lactose, gelatin. Notably, butanol extract and resveratrol present in the P. cuspidatum demonstrated IC50 values 15.8±2.6 μg/ml and 124±6.7 μg/ml, respectively.

155

6.

2017

Chinese patent (CN106962933A

Fang et al.

The formulation is comprised of extracts from F. nelumbinis and N. nucifera (leaf), C. sinensis (leaf), C. obtusifolia (seed), and V. vinifera (seed). This blend exhibited anti-obesity properties through the inhibition lipase (PL), contributing to weight reduction and the control of lipid metabolism, intestinal flora.