Generic placeholder image

Current Drug Targets


ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Review Article

Do the Natural Chemical Compounds Interact with the Same Targets of Current Pharmacotherapy for Weight Management?-A Review

Author(s): Shiqi Luo, George Binh Lenon*, Harsharn Gill, Heidi Yuen, Angela Wei Hong Yang, Andrew Hung and Linh Toan Nguyen

Volume 20 , Issue 4 , 2019

Page: [399 - 411] Pages: 13

DOI: 10.2174/1389450119666180830125958

Price: $65


Background: Obesity has become a worldwide health concern. Pharmacotherapies are now being introduced because lifestyle modifications alone are insufficient for weight management. The treatment outcomes of current approved anti-obesity agents are not satisfying due to drug-related intolerances. And so natural therapies including herbal medicines are popular alternatives for weight reduction; however, there are limited studies about their mechanism of actions.

Methods: Five databases (PubMed, Scopus, Google Scholar, Science Direct, Proquest) were searched to investigate the targets and safety profiles of the current and past anti-obesity drugs that have been approved by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) as well as the commonly used off-label agents. The targets for weight-loss natural products and their principle bioactive components have also been searched. Only articles in English were included.

Results: The targets for current anti-obesity single agents include pancreatic lipase, Glucagon Like Peptide-1(GLP-1) receptor, and serotonin 2C (5-HT2C) receptor. Potential targets such as amylin, pancreatic alpha amylase, leptin receptor, melanocortin receptor 4 receptor (MC4R), Peroxisome Proliferator- Activated Receptors gamma (PPAR γ), endocannabinoid 1 (CB1) receptor and Adenosine Monophosphate (AMP)-Activated Protein Kinase (AMPK) were discussed in various studies. Natural compounds have been found to interact with targets like pancreatic lipase, pancreatic alpha amylase, AMPK and PPAR γ to achieve weight reduction.

Conclusion: Current pharmacotherapies and natural chemical compounds do act on same targets. Further investigations on the interactions between herbal compounds and the above targets are essential for the development of novel weight-loss therapies.

Keywords: Obesity, weight management, pharmacotherapy, herbal medicine, medicinal plants, phytochemical, targets, current anti-obesity agents.

Graphical Abstract
Xu Y, Zhang M, Wu T, et al. The anti-obesity effect of green tea polysaccharides, polyphenols and caffeine in rats fed with a high-fat diet. Food Funct 2015; 6(1): 297-304.
World Health Organization (WHO): Obesity and Overweight Fact Sheet. Available at:. fs311/en/ [Accessed August 10, 2017].
Er E. Obesity and weight management: the efficacy of herbal products as therapeutic agents Nutr Food Technol 2016; 2(3).
Ahn JH, Kim ES, Lee C, et al. Chemical constituents from Nelumbo nucifera leaves and their anti-obesity effects. Bioorg Med Chem Lett 2013; 23(12): 3604-8.
Sheng L, Qian Z, Zheng S, et al. Mechanism of hypolipidemic effect of crocin in rats: crocin inhibits pancreatic lipase. Eur J Pharmacol 2006; 543(1-3): 116-22.
Furuyashiki T, Nagayasu H, Aoki Y, et al. Tea Catechin suppresses adipocyte differentiation accompanied by down-regulation of PPARγ2 and C/EBPα in 3T3-L1 Cells. Biosci Biotechnoland Biochem 2014; 68(11): 2353-9.
Mancini MC. De melo ME. The burden of obesity in the current world and the new treatments available: Focus on liraglutide 3.0 mg. Diabetol Metab Syndr 2017; 9: 44.
Trigueros L, Pena S, Ugidos AV, et al. Food ingredients as anti-obesity agents: a review. Crit Rev Food Sci Nutr 2013; 53(9): 929-42.
Rankin W, Wittert G. Anti-obesity drugs. Curr Opin Lipidol 2015; 26(6): 536-43.
Chen Y. Regulation of food intake and the development of anti-obesity drugs. Drug Discov Ther 2016; 10(2): 62-73.
Lucas KH, Kaplan-Machlis B. Orlistat-a novel weight loss therapy. Ann Pharmacother 2001; 35(3): 314-28.
Elangbam C. Current strategies in the development of anti-obesity drugs and their safety concerns. Vet Pathol 2009; 46(1): 10-24.
Heck AM, Yanovski JA, Calis KA. Orlistat, a new lipase inhibitor for the management of obesity J Hum Pharmacol. Drug Ther 2000; 20(3): 270-9.
Bays H. Lorcaserin and adiposopathy: 5-HT2c agonism as a treatment for ‘sick fat’and metabolic disease. Expert Rev Cardiovasc Ther 2009; 7(11): 1429-45.
Thomsen WJ, Grottick AJ, Menzaghi F, et al. Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J Pharmacol Exp Ther 2008; 325(2): 577-87.
Adan RH. Mechanisms underlying current and future anti-obesity drugs. Trends Neurosci 2013; 36(2): 133-40.
Cooke D, Bloom S. The obesity pipeline: Current strategies in the development of anti-obesity drugs. Nat Rev Drug Discov 2006; 5(11): 919-31.
Moyers SB. Medications as adjunct therapy for weight loss: Approved and off-label agents in use. J Am Diet Assoc 2005; 105(6): 948-59.
Nammi SKS, Chinnala KM, Boini KM. Obesity: An overview on its current perspectives and treatment options. Nutr J 2004; 3(1): 3.
Haslam D. Weight management in obesity - past and present. Int J Clin Pract 2016; 70(3): 206-17.
Onakpoya IJ, Heneghan CJ, Aronson JK. Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: A systematic review. BMC Med 2016; 14(1): 191.
Gadde KMXG. Bupropion for weight reduction. Expert Rev Neurother 2007; 7(1): 17-24.
Rodgers RJ, Tschop MH, Wilding JP. Anti-obesity drugs: Past, present and future. Dis Model Mech 2012; 5(5): 621-6.
Kushner RF. Anti-obesity drugs. Expert Opin Pharmacother 2008; 9(8): 1339-50.
Jorsal T, Rungby J, Knop FK, et al. GLP-1 and amylin in the treatment of obesity. Curr Diab Rep 2016; 16(1): 1.
Bailey CJ. Metformin: Historical overview. Diabetologia 2017; 60(9): 1566-76.
Igel LI, Sinha A, Saunders KH, et al. Metformin: An old therapy that deserves a new indication for the treatment of obesity. Curr Atheroscler Rep 2016; 18(4): 16.
Hur KY, Lee MS. New mechanisms of metformin action: Focusing on mitochondria and the gut. J Diabetes Investig 2015; 6(6): 600-9.
Taylor SI, Blau JE, Rother KI. SGLT2 Inhibitors may predispose to ketoacidosis. J Clin Endocrinol Metab 2015; 100(8): 2849-52.
Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015; 100(2): 342-62.
Hollander P, Bays HE, Rosenstock J, et al. Coadministration of canagliflozin and phentermine for weight management in overweight and obese individuals without diabetes: A randomized clinical trial. Diabetes Care 2017; 40(5): 632-9.
Chowdhary M, Kabbani AA, Chhabra A. Canagliflozin-induced pancreatitis: A rare side effect of a new drug. Ther Clin Risk Manag 2015; 11: 991-4.
Lee SH, Paz-Filho G, Mastronardi C, et al. Is increased antidepressant exposure a contributory factor to the obesity pandemic? Transl Psychiatry 2016; 6: 759.
Habibuddin MT. Pharmacological management of obesity: Past, present and future. Saudi J Obes 2014; 2(1): 3.
Sun BK, Kim JH, Choi JS, et al. Fluoxetine decreases the proliferation and adipogenic differentiation of human adipose-derived stem cells. Int J Mol Sci 2015; 16(7): 16655-68.
Brownley KA, Peat CM, La Via M, et al. Pharmacological approaches to the management of binge eating disorder. Drugs 2015; 75(1): 9-32.
Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: An updated systematic review. Drugs 2009; 69(13): 1777-98.
Diepvens K, Westerterp KR, Westerterp-Plantenga MS. Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea. Am J Physiol Regul Integr Comp Physiol 2007; 292(1): R77-85.
Harpaz E, Tamir S, Weinstein A, et al. The effect of caffeine on energy balance. J Basic Clin Physiol Pharmacol 2017; 28(1): 1-10.
Saper RBED, Phillips RS. Common dietary supplements for weight loss. Am Fam Physician 2004; 70: 1731-40.
Grove KA, Sae-tan S, Kennett MJ, et al. (-)-Epigallocatechin-3-gallate inhibits pancreatic lipase and reduces body weight gain in high fat-fed obese mice. Obesity 2012; 20(11): 2311-3.
Rocha A, Bolin AP, Cardoso CA, et al. Green tea extract activates AMPK and ameliorates white adipose tissue metabolic dysfunction induced by obesity. Eur J Nutr 2016; 55(7): 2231-44.
Quinhoneiro DG, Nicoletti CF, Pinhel MS, et al. Green tea supplementation upregulates uncoupling protein 3 expression in severe obese women adipose tissue but does not promote weight loss. Int J Food Sci Nutr 2018; 1-8.
Zhu YT, Jia YW, Liu YM, et al. Lipase ligands in Nelumbo nucifera leaves and study of their binding mechanism. J Agric Food Chem 2014; 62(44): 10679-86.
Ono Y, Hattori E, Fukaya Y, et al. Anti-obesity effect of Nelumbo nucifera leaves extract in mice and rats. J Ethnopharmacol 2006; 106(2): 238-44.
Rupasinghe HP, Sekhon-Loodu S, Mantso T, et al. Phytochemicals in regulating fatty acid beta-oxidation: Potential underlying mechanisms and their involvement in obesity and weight loss. Pharmacol Ther 2016; 165: 153-63.
Park UH, Jang JS, Sung MR, et al. Negative regulation of adipogenesis by kaempferol, a component of Rhizoma Polygonati falcatum in 3T3-L1 cells. Biol Pharm Bull 2012; 35(9): 1525-33.
Kang SW, Kang SI, Shin HS, et al. Sasa quelpaertensis Nakai extract and its constituent p-coumaric acid inhibit adipogenesis in 3T3-L1 cells through activation of the AMPK pathway. Food Chem Toxicol 2013; 59: 380-5.
Liu W, Zheng Y, Han L, et al. Saponins (Ginsenosides) from stems and leaves of Panax quinquefolium prevented high-fat diet-induced obesity in mice. Phytomedicine 2008; 15(12): 1140-5.
Alvala R, Alvala M, Sama V, et al. Scientific evidence for traditional claim of anti-obesity activity of Tecomella undulata bark. J Ethnopharmacol 2013; 148(2): 441-8.
Ramirez G, Zamilpa A, Zavala M, et al. Chrysoeriol and other polyphenols from Tecoma stans with lipase inhibitory activity. J Ethnopharmacol 2016; 185: 1-8.
Kim J, Jang DS, Kim H, et al. Anti-lipase and lipolytic activities of ursolic acid isolated from the roots of Actinidia arguta. Arch Pharm Res 2009; 32(7): 983-7.
Papathanasopoulos A, Camilleri M. Dietary fiber supplements: Effects in obesity and metabolic syndrome and relationship to gastrointestinal functions. Gastroenterology 2010; 138(1): 65-72.
El Khoury D, Cuda C, Luhovyy BL, et al. Beta glucan: Health benefits in obesity and metabolic syndrome. J Nutr Metab 2012; 2012: 851362.
Ha DT, Trung TN, Phuong TT, et al. The selected flavonol glycoside derived from Sophorae Flos improves glucose uptake and inhibits adipocyte differentiation via activation AMPK in 3T3-L1 cells. Bioorg Med Chem Lett 2010; 20(20): 6076-81.
Birari RB, Bhutani KK. Pancreatic lipase inhibitors from natural sources: unexplored potential. Drug Discov Today 2007; 12(19-20): 879-89.
Barrett ML, Udani JK. A proprietary alpha-amylase inhibitor from white bean (Phaseolus vulgaris): A review of clinical studies on weight loss and glycemic control. Nutr J 2011; 10(1): 24.
Mukherjee R, Jow L, Croston GE, et al. Identification, characterization, and tissue distribution of human Peroxisome Proliferator-Activated Receptor (PPAR) isoforms PPARγ2 versus PPARγ1 and activation with retinoid X receptor agonists and antagonists. J Biochem 1997; 272(12): 8071-6.
Spiegelman BM. JS F. Adipogenesis and obesity: Rounding out the big picture. Cell 1996; 87(3): 377-89.
Daval M, Foufelle F, Ferre P. Functions of AMP-activated protein kinase in adipose tissue. J Physiol 2006; 574: 55-62.
Hardie DG. AMPK: A key regulator of energy balance in the single cell and the whole organism. Int J Obes (Lond) 2008; 4: 7-12.
Ono M, Fujimori K. Antiadipogenic effect of dietary apigenin through activation of AMPK in 3T3-L1 cells. J Agric Food Chem 2011; 59(24): 13346-52.
Reda TK, Geliebter A, Pi-Sunyer FX. Amylin, food intake, and obesity. Obesity 2002; 10(10): 1087-91.
Rezai-Zadeh K, Yu S, Jiang Y, et al. Leptin receptor neurons in the dorsomedial hypothalamus are key regulators of energy expenditure and body weight, but not food intake. Mol Metab 2014; 3(7): 681-93.
Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: A review. Obes Rev 2007; 8(1): 21-34.
Delhanty PJ, Bouw E, Huisman M, et al. Functional characterization of a new human melanocortin-4 receptor homozygous mutation (N72K) that is associated with early-onset obesity. Mol Biol Rep 2014; 41(12): 7967-72.
Harrold JA, Williams G. Melanocortin-4 receptors, beta-MSH and leptin: Key elements in the satiety pathway. Peptides 2006; 27(2): 365-71.
Farooqi IS, Keogh JM, Yeo GS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003; 348(12): 1085-95.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy