ReviewPossible anti-obesity therapeutics from nature – A review
Graphical abstract
A wide variety of natural materials have been explored for the treatment of obesity. The objective of this review is to survey greater part of natural products with anti-obesity activity, and to review scientific data such as experimental methodology, active components and their mechanisms of action exhibiting anti-obesity activity.
Introduction
On a global scale, obesity has reached epidemic proportions and is a major contributor to the global burden of chronic disease and disability. Currently, more than one billion adults worldwide are overweight and at least 300 million of them are clinically obese (WHO, 2009).
Two different types of obesity-treatment drugs are currently available on the market (Chaput et al., 2007). One of these is orlistat (Xenical), which reduces intestinal fat absorption through inhibition of pancreatic lipase (Ballinger and Peikin, 2002, Drew et al., 2007, Hutton and Fergusson, 2004, Thurairajah et al., 2005). The other is sibutramine (Reductil), which is an anorectic, or appetite suppressant (Lean, 2001, Poston and Foreyt, 2004, Tziomalos et al., 2009). Both drugs have side-effects, including increased blood pressure, dry mouth, constipation, headache, and insomnia (de Simone and D’Addeo, 2008, Karamadoukis et al., 2009, Slovacek et al., 2008, Thurairajah et al., 2005). A number of anti-obesity drugs are currently undergoing clinical development, including centrally-acting drugs (e.g. radafaxine and oleoyl-estrone), drugs targeting peripheral episodic satiety signals (e.g. rimonabant and APD356), drugs blocking fat absorption (e.g. cetilistat and AOD9604), and human growth hormone fragments (Halford, 2006, Melnikova and Wages, 2006).
At present, because of dissatisfaction with high costs and potentially hazardous side-effects, the potential of natural products for treating obesity is under exploration, and this may be an excellent alternative strategy for developing future effective, safe anti-obesity drugs (Mayer et al., 2009, Nakayama et al., 2007, Park et al., 2005). A variety of natural products, including crude extracts and isolated compounds from plants, can induce body weight reduction and prevent diet-induced obesity. Therefore, they have been widely used in treating obesity (Han et al., 2005a, Moro and Basile, 2000, Rayalam et al., 2008).
A wealth of information indicates numerous bioactive components from nature are potentially useful in obesity treatments. A good example of such is the polyphenols. These show strong anti-obesity activity and include apigenin, genistein, and the catechins (Rayalam et al., 2008, Thielecke and Boschmann, 2009, Wolfram et al., 2006).
To date, despite the appearance of several excellent reviews of anti-obesity agents in the literature, no reviews have focused on summarizing real, natural-product data on anti-obesity activity, active compound types, and mechanisms of action. In 2000, Moro and Basile reviewed the use of certain well-known medicinal plants that had claimed to be useful in treating obesity (Moro and Basile, 2000). Five years later, Han et al., 2005a reviewed the anti-obesity effects of natural products from more diverse sources. More recently, the review of anti-obesity phytochemicals by Rayalam et al. (2008) focused on adipocyte life cycle regulation. However, these reviews do not provide updates from the literature regarding various natural products that have anti-obesity effects.
Therefore, in this review, we surveyed natural products with anti-obesity potential and reviewed the scientific data, including experimental methodologies, active components, and mechanisms of action against obesity. A growing body of evidence indicates that natural products having anti-obesity effects can be arranged into five categories based on their distinct mechanisms; they produce (1) decreased lipid absorption, (2) decreased energy intake, (3) increased energy expenditure, (4) decreased pre-adipocyte differentiation and proliferation, or (5) decreased lipogenesis and increased lipolysis. Therefore, in this review, we addressed naturally-occurring compounds possessing anti-obesity activity addressed by categorizing them per these mechanisms.
Section snippets
Lipase inhibitory effect
Among treatments for obesity, one of the most promising strategies in the effort to reduce energy intake through gastrointestinal mechanisms, without altering the central mechanisms, is the development of nutrient digestion and absorption inhibitors (Birari and Bhutani, 2007). Dietary fat is not directly absorbed by the intestine unless the fat has been subjected to the action of pancreatic lipase. Therefore, pancreatic lipase is one of the most widely studied mechanisms for determining natural
Conclusions
Anti-obesity pharmacological treatment should be administered only when considered safe and effective for obese subject. Over the past 30 years, few obesity-treatment drugs have been developed or approved. Only two drugs are currently available, and some drugs have been withdrawn from the market due to serious side-effects. Sibutramine and orlistat may cause weight loss of up to 10% when used in combination with dietary, behavioral, and exercise therapy. The need exists for anti-obesity drugs
Acknowledgements
This research was supported by the Mid-Career Researcher Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education, Science, and Technology (Grant Number R01-2008-000-10277-0). The author also wishes to thank Ms. J.S. Lee and Ms. H.S. Hwang for their helpful literature collection and arrangements.
Jong Won Yun received his MSc degree in 1987 from the Department of Chemical Engineering, Pusan National University, Pusan, Korea. He was employed for six years as research scientist in CJ Cheiljedang R&D Center. The focus of his laboratory was to development of functional sweeteners such as fructooligosaccharides and palatinose from natural resources. In 1992, he started his PhD study at the Department of Chemical Engineering, Pusan National University. The focus of his PhD studies was
References (288)
- et al.
Resveratrol inhibits TNF-α-induced changes of adipokines in 3T3-L1 adipocytes
Biochem. Biophys. Res. Commun.
(2007) - et al.
Effect of Hibiscus sabdariffa on obesity in MSG mice
J. Ethnopharmacol.
(2007) - et al.
Soy protein isolate and its hydrolysate reduce body fat of dietary obese rats and genetically obese mice (yellow KK)
Nutrition
(2000) - et al.
Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue
J. Nutr.
(2001) - et al.
Effect of sterols and fatty acids on growth and triglyceride accumulation in 3T3-L1 cells
J. Nutr. Biochem.
(2000) - et al.
Orlistat: its current status as an anti-obesity drug
Eur. J. Pharmacol.
(2002) - et al.
Pancreatic lipase inhibitors from natural sources: unexplored potential
Drug Discov. Today
(2007) - et al.
Activity of two different polyglucosamines, L112® and FF45®, on body weight in male rats
Eur. J. Pharmacol.
(2007) - et al.
Consumption of an oil composed of medium chain triacyglycerols, phytosterols, and N-3 fatty acids improves cardiovascular risk profile in overweight women
Metabolism
(2003) - et al.
Recent findings of green tea extract AR25 (exolise) and its activity for the treatment of obesity
Phytomedicine
(2002)
Molecular regulation of adipocyte differentiation
Semin. Cell Dev. Biol.
Sibutramine: balancing weight loss benefit and possible cardiovascular risk
Nutr. Metab. Cardiovasc. Dis.
Anti-hyperglycemic effects of ginseng: comparison between root and berry
Phytomedicine
Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans
Am. J. Clin. Nutr.
Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice
J. Nutr.
Comparative effects of intraduodenal infusions of lauric and oleic acids on antropyloroduodenal motility, plasma cholecystokinin and peptide YY, appetite, and energy intake in healthy men
Am. J. Clin. Nutr.
Effects of combined oleoyl-estrone and rimonabant on overweight rats
J. Pharmacol. Sci.
Obesity wars: molecular progress confronts an expanding epidemic
Cell
Oleoylethanolamide, an endogenous PPAR-α agonist, lowers body weight and hyperlipidemia in obese rats
Neuropharmacology
Chitosan supplementation and fat absorption in men and women
J. Am. Diet. Assoc.
Overfeeding with medium-chain triglyceride diet results in diminished deposition of fat
Am. J. Clin. Nutr.
Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, 3-adrenergic agonists, and leptin
J. Biol. Chem.
An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion
Cell
Oleoylethanolamide stimulates lipolysis by activating the nuclear receptor peroxisome proliferator-activated receptor α (PPAR-α)
J. Biol. Chem.
The lipase inhibitor tetrahydrolipstatin binds covalently to the putative active site serine of pancreatic lipase
J. Biol. Chem.
Platycodi radix affects lipid metabolism in mice with high fat diet-induced obesity
J. Nutr.
Saponins from Platycodi radix ameliorate high fat diet-induced obesity in mice
J. Nutr.
Flavan dimers with lipase inhibitory activity from Cassia nomame
Phytochemistry
Effects of Toona sinensis leaf extract on lipolysis in differentiated 3T3-L1 adipocytes
Kaohsiung J. Med. Sci.
Berberine increases expression of GATA-2 and GATA-3 during inhibition of adipocyte differentiation
Phytomedicine
Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway
Biochem. Biophys. Res. Commun.
Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials
Am. J. Clin. Nutr.
Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase
Biochem. Biophys. Res. Commun.
A soybean peptide isolate diet promotes postprandial carbohydrate oxidation and energy expenditure in type II diabetic mice
J. Nutr.
Daisuke uemura (−)-ternatin inhibits adipogenesis and lipid metabolism in 3T3-L1 cells
Peptides
Red yeast rice extracts suppress adipogenesis by down-regulating adipogenic transcription factors and gene expression in 3T3-L1 cells
Life Sci.
Rehmannia inhibits adipocyte differentiation and adipogenesis
Biochem. Biophys. Res. Commun.
Effects of Aralia mandshurica and Engelhardtia chrysolepis extracts on some parameters of lipid metabolism in women with nondiabetic obesity
Bull. Exp. Biol. Med.
Antiobesity effect of Kochujang (Korean fermented red pepper paste) extract in 3T3-L1 adipocytes
J. Med. Food
Antiobesity effects of Isaria sinclairii by repeated oral treatment in obese Zucker rats over a 4-month period
J. Toxicol. Environ. Health A
Ajoene exerts potent effects in 3T3-L1 adipocytes by inhibiting adipogenesis and inducing apoptosis
Phytother. Res.
Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component
Diabetes
Active compounds from Lagerstroemia speciosa, insulin-like glucose uptake-stimulatory/inhibitory and adipocyte differentiation-inhibitory activities in 3T3-L1 cells
J. Agric. Food Chem.
Effect of orally and intraperitoneally administered plant lectins on food consumption of rats
Acta Physiol. Hung.
Current and investigational antiobesity agents and obesity therapeutic treatment targets
Obes. Res.
Screening of lipase inhibitors from marine algae
Lipids
Catechol O-methyltransferase. 5. Structure–activity relationships for inhibition by flavonoids
J. Med. Chem.
The effects of epigallocatechin-3-gallate on thermogenesis and fat oxidation in obese men: a pilot study
J. Am. Coll. Nutr.
Bezafibrate reduces mRNA levels of adipocyte markers and increases fatty acid oxidation in primary culture of adipocytes
Diabetes
Brown adipose tissue: function and physiological significance
Physiol. Rev.
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Jong Won Yun received his MSc degree in 1987 from the Department of Chemical Engineering, Pusan National University, Pusan, Korea. He was employed for six years as research scientist in CJ Cheiljedang R&D Center. The focus of his laboratory was to development of functional sweeteners such as fructooligosaccharides and palatinose from natural resources. In 1992, he started his PhD study at the Department of Chemical Engineering, Pusan National University. The focus of his PhD studies was production of fructooligosaccharides and isomaltooligosaccharides by several transferases. In 1995, following his PhD study, he was employed as Assistant Professor at the Department of Biotechnology, Daegu University, where his work is focused on production of biomaterials with anti-diabetic and anti-obesity activity. Recently, he has studied clinical proteomics to discover anti-obesity biomarkers in response to anti-obesity drugs or medicinal compounds with anti-obesity activity. He is acting as an editor or editorial board member of several international journals including Journal of Chemical Technology and Biotechnology, Journal of Microbiology and Biotechnology, and Biotechnology and Bioprocess Engineering. He has published 130 international papers and 54 domestic papers in the fields of functional biomaterials and proteomics.