Generic placeholder image

The Natural Products Journal

Editor-in-Chief

ISSN (Print): 2210-3155
ISSN (Online): 2210-3163

Review Article

Natural Compounds Promoting Weight Loss: Mechanistic Insights from the Point of View of the Medicinal Chemist

Author(s): Giovanni Ribaudo*, Alberto Ongaro and Giuseppe Zagotto

Volume 9, Issue 2, 2019

Page: [78 - 85] Pages: 8

DOI: 10.2174/2210315508666180816091434

Price: $65

Abstract

Background: The adipose tissue acts as a buffer storing and releasing energy according to the needs of the body. In a non-physiological context, the development of obesity is related to an unbalance in the homeostasis between calories intake and energy consumption.

Objectives: This review focuses on the natural compounds and the herbal extracts used in dietary supplements that are claimed to suppress appetite and promote weight loss. Such compounds or mixture of compounds act through different molecular mechanisms that will be discussed from the point of view of the Medicinal Chemist. The reader will be also briefly updated on the recurring adulteration cases that affect the market of dietary supplements.

Methods: The bibliographic research was performed using online scientific databases (PubMed, Reaxys, Scopus) exploiting different keywords and logical operators to lay the bases for an accurate, quality criteria-based literature update.

Results: Over 70 papers were selected for the preparation of this review, preferring the reports that are supported by pre-clinical and clinical data.

Conclusion: Activity on adrenergic receptors, modulation of adenosine receptors, interference with glucose and lipid metabolism, regulation of adipocyte cell cycle and inhibition of phosphodiesterases are the main molecular mechanisms by which different natural compounds act in promoting weight loss.

Keywords: Weight loss, nutraceuticals, appetite suppression, plant extracts, adulteration, analytical chemistry.

Graphical Abstract
[1]
Benatrehina, P.A.; Pan, L.; Naman, C.B.; Li, J.; Kinghorn, A.D. Usage, biological activity, and safety of selected botanical dietary supplements consumed in the United States. J. Tradit. Complement. Med., 2018, 8(2), 267-277.
[2]
Clarke, T.C.; Black, L.I.; Stussman, B.J.; Barnes, P.M.; Nahin, R.L. Trends in the use of complementary health approaches among adults: United States, 2002-2012. Natl. Health Stat. Rep., 2015, 2015(79), 1-16.
[3]
Bailey, R.L.; Gahche, J.J.; Miller, P.E.; Thomas, P.R.; Dwyer, J.T. Why US adults use dietary supplements. JAMA Intern. Med., 2013, 173(5), 355-361.
[4]
Brown, A.C. Kidney toxicity related to herbs and dietary supplements: Online table of case reports. Part 3 of 5 series. Food Chem. Toxicol, 2017, 107 (Pt A), 502-519.
[5]
Washington, A.E.; Lipstein, S.H. The patient-centered outcomes research institute promoting better information, decisions, and health. N. Engl. J. Med., 2011, 365(15), e31.
[6]
Dastjerdi, A.G.; Akhgari, M.; Kamali, A.; Mousavi, Z. Principal component analysis of synthetic adulterants in herbal supplements advertised as weight loss drugs. Complement. Ther. Clin. Pract., 2018, 31, 236-241.
[7]
Carrageta, D.F.; Dias, T.R.; Alves, M.G.; Oliveira, P.F.; Monteiro, M.P.; Silva, B.M. Anti-obesity potential of natural methylxanthines. J. Funct. Foods, 2018, 43, 84-94.
[8]
Yimam, M.; Jiao, P.; Hong, M.; Brownell, L.; Lee, Y.C.; Hyun, E.J.; Kim, H.J.; Kim, T.W.; Nam, J.B.; Kim, M-R. Evaluation of natural product compositions for appetite suppression. J. Diet. Suppl., 2019, 16(1), 86-104.
[9]
Saely, C.H.; Geiger, K.; Drexel, H. Brown versus white adipose tissue: A mini-review. Gerontology, 2012, 58(1), 15-23.
[10]
Hosseini, B.; Saedisomeolia, A.; Wood, L.G.; Yaseri, M.; Tavasoli, S. Effects of pomegranate extract supplementation on inflammation in overweight and obese individuals: A randomized controlled clinical trial. Complement. Ther. Clin. Pract., 2016, 22, 44-50.
[11]
Johnson, C.L.; Dohrmann, S.M.; Kerckove, V.; Diallo, M.S.; Clark, J.; Mohadjer, L.K.; Burt, V.L. National health and nutrition examination survey: National youth fitness survey estimation procedures, 2012. Vital Health Stat. 2, 2014, 2014(168), 1-25.
[12]
Cebi, N.; Yilmaz, M.T.; Sagdic, O.; Yuce, H.; Yelboga, E. Prediction of peroxide value in omega-3 rich microalgae oil by ATR-FTIR spectroscopy combined with chemometrics. Food Chem., 2017, 225, 188-196.
[13]
Rayalam, S.; Della-Fera, M.A.; Baile, C.A. Phytochemicals and regulation of the adipocyte life cycle. J. Nutr. Biochem., 2008, 19(11), 717-726.
[14]
Rodríguez, J.E.; Campbell, K.M. Past, present, and future of pharmacologic therapy in obesity. Prim. Care, 2016, 43(1), 61-67.
[15]
Zare, R.; Heshmati, F.; Fallahzadeh, H.; Nadjarzadeh, A. Effect of cumin powder on body composition and lipid profile in overweight and obese women. Complement. Ther. Clin. Pract., 2014, 20(4), 297-301.
[16]
Burke, F.M. Red yeast rice for the treatment of dyslipidemia. Curr. Atheroscler. Rep., 2015, 17(4), 495.
[17]
Langin, D. Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome. Pharmacol. Res., 2006, 53(6), 482-491.
[18]
Greenway, F.L. The safety and efficacy of pharmaceutical and herbal caffeine and ephedrine use as a weight loss agent. Obes. Rev., 2001, 2(3), 199-211.
[19]
Diepvens, K.; Westerterp, K.R.; Westerterp-Plantenga, M.S. 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-R85.
[20]
Acheson, K.; Jéquier, E.; Wahren, J. Influence of beta-adrenergic blockade on glucose-induced thermogenesis in man. J. Clin. Invest., 1983, 72(3), 981-986.
[21]
Dulloo, A.G.; Duret, C.; Rohrer, D.; Girardier, L.; Mensi, N.; Fathi, M.; Chantre, P.; Vandermander, J. 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., 1999, 70(6), 1040-1045.
[22]
Yoshioka, M.; Lim, K.; Kikuzato, S.; Kiyonaga, A.; Tanaka, H.; Shindo, M.; Suzuki, M. Effects of red-pepper diet on the energy metabolism in men. J. Nutr. Sci. Vitaminol. (Tokyo), 1995, 41(6), 647-656.
[23]
Kawada, T.; Watanabe, T.; Takaishi, T.; Tanaka, T.; Iwai, K. Capsaicin-induced beta-adrenergic action on energy metabolism in rats: influence of capsaicin on oxygen consumption, the respiratory quotient, and substrate utilization. Proc. Soc. Exp. Biol. Med., 1986, 183(2), 250-256.
[24]
Borchardt, R.T.; Wu, Y.S. Potential inhibitors of s-adeno-sylmethionine-dependent methyltransferases. 3. modifications of the sugar portion of s-adenosylhomocysteine. J. Med. Chem., 1975, 18(3), 300-304.
[25]
Olah, M.E.; Stiles, G.L. Adenosine receptor subtypes: Characterization and therapeutic regulation. Annu. Rev. Pharmacol. Toxicol., 1995, 35(1), 581-606.
[26]
Trost, T.; Schwabe, U. Adenosine receptors in fat cells. identification by (-)-N6-[3H]phenylisopropyladenosine binding. Mol. Pharmacol., 1981, 19(2), 228-235.
[27]
Dhalla, A.K.; Chisholm, J.W.; Reaven, G.M.; Belardinelli, L. A1 adenosine receptor: Role in diabetes and obesity. Handb. Exp. Pharmacol., 2009, 2009(193), 271-295.
[28]
Vannucci, S.J.; Klim, C.M.; Martin, L.F.; LaNoue, K.F. A1-adenosine receptor-mediated inhibition of adipocyte adenylate cyclase and lipolysis in zucker rats. Am. J. Physiol. Metab., 1989, 257(6), E871-E878.
[29]
Fredholm, B.B.; Irenius, E.; Kull, B.; Schulte, G. Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in chinese hamster ovary cells. Biochem. Pharmacol., 2001, 61(4), 443-448.
[30]
Gnad, T.; Scheibler, S.; von Kügelgen, I.; Scheele, C.; Kilić, A.; Glöde, A.; Hoffmann, L.S.; Reverte-Salisa, L.; Horn, P.; Mutlu, S. Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors. Nature, 2014, 516(7531), 395-399.
[31]
Xie, Y.; Zhang, X.; Yang, J.; Kim, S.; Hong, S.; Giesy, J.P.; Yim, U.H.; Shim, W.J.; Yu, H.; Khim, J.S. eDNA-based bioassessment of coastal sediments impacted by an oil spill. Environ. Pollut., 2018, 238, 739-748.
[32]
Badshah, H.; Ullah, I.; Kim, S.E.; Kim, T.; Lee, H.Y.; Kim, M.O. Anthocyanins attenuate body weight gain via modulating neuropeptide Y and GABAB1 receptor in rats hypothalamus. Neuropeptides, 2013, 47(5), 347-353.
[33]
Tsuda, T.; Horio, F.; Uchida, K.; Aoki, H.; Osawa, T. Dietary cyanidin 3-O-Beta-D-Glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. J. Nutr., 2003, 133(7), 2125-2130.
[34]
Wu, T.; Yin, J.; Zhang, G.; Long, H.; Zheng, X. Mulberry and cherry anthocyanin consumption prevents oxidative stress and inflammation in diet-induced obese mice. Mol. Nutr. Food Res., 2016, 60(3), 687-694.
[35]
Avula, B.; Wang, Y.H.; Pawar, R.S.; Shukla, Y.J.; Schaneberg, B.; Khan, I.A. Determination of the appetite suppressant P57 in hoodia gordonii plant extracts and dietary supplements by liquid chromatography/electrospray ionization mass spectrometry (LC-MSD-TOF) and LC-UV methods. J. AOAC Int., 2006, 89(3), 606-611.
[36]
MacLean, D.B.; Luo, L.G. Increased ATP content/production in the hypothalamus may be a signal for energy-sensing of satiety: Studies of the anorectic mechanism of a plant steroidal glycoside. Brain Res., 2004, 1020(1-2), 1-11.
[37]
Klontz, K.C.; Timbo, B.B.; Street, D. Consumption of dietary supplements containing Citrus aurantium (Bitter Orange)-2004 California Behavioral Risk Factor Surveillance Survey (BRFSS). Ann. Pharmacother., 2006, 40(10), 1747-1751.
[38]
Kuriyan, R.; Raj, T.; Srinivas, S.K.; Vaz, M.; Rajendran, R.; Kurpad, A.V. Effect of Caralluma fimbriata extract on appetite, food intake and anthropometry in adult indian men and women. Appetite, 2007, 48(3), 338-344.
[39]
Wagner, J.D.; Cefalu, W.T.; Anthony, M.S.; Litwak, K.N.; Zhang, L.; Clarkson, T.B. Dietary soy protein and estrogen replacement therapy improve cardiovascular risk factors and decrease aortic cholesteryl ester content in ovariectomized cynomolgus monkeys. Metabolism, 1997, 46(6), 698-705.
[40]
Riccardi, G.; Rivellese, A.A. Effects of dietary fiber and carbohydrate on glucose and lipoprotein metabolism in diabetic patients. Diabetes Care, 1991, 14(12), 1115-1125.
[41]
Bo-Linn, G.W.; Santa Ana, C.A.; Morawski, S.G.; Fordtran, J.S. Starch blockers - Their effect on calorie absorption from a high-starch meal. N. Engl. J. Med., 1982, 307(23), 1413-1416.
[42]
Celleno, L.; Tolaini, M.V.; D’Amore, A.; Perricone, N.V.; Preuss, H.G. A dietary supplement containing standardized Phaseolus vulgaris extract influences body composition of overweight men and women. Int. J. Med. Sci., 2007, 4(1), 45-52.
[43]
Abidov, M.T.; Rio, M.J.; Ramazanov, T.Z.; Klimenov, A.L.; Dzhamirze, S.; Kalyuzhin, O.V. Effects of Aralia mandshurica and Engelhardtia chrysolepis extracts on some parameters of lipid metabolism in women with nondiabetic obesity. Bull. Exp. Biol. Med., 2006, 141(3), 343-346.
[44]
Moreno, L.A.; Tresaco, B.; Bueno, G.; Fleta, J.; Rodríguez, G.; Garagorri, J.M.; Bueno, M. Psyllium fibre and the metabolic control of obese children and adolescents. J. Physiol. Biochem., 2003, 59(3), 235-242.
[45]
Han, L.K.; Sumiyoshi, M.; Zhang, J.; Liu, M.X.; Zhang, X.F.; Zheng, Y.N.; Okuda, H.; Kimura, Y. Anti-obesity action Ofsalix matsudana leaves (Part 1). Anti-obesity action by polyphenols ofsalix matsudana in high fat-diet treated rodent animals. Phytother. Res., 2003, 17(10), 1188-1194.
[46]
Urizar, N.L.; Moore, D.D. GUGULIPID: A natural cholesterol-lowering agent. Annu. Rev. Nutr., 2003, 23(1), 303-313.
[47]
Vaskonen, T.; Mervaala, E.; Seppänen-Laakso, T.; Karppanen, H. Diet enrichment with calcium and magnesium enhances the cholesterol-lowering effect of plant sterols in obese zucker rats. Nutr. Metab. Cardiovasc. Dis., 2001, 11(3), 158-167.
[48]
Hirafuji, M.; Machida, T.; Hamaue, N.; Minami, M. cardiovascular protective effects of N-3 polyunsaturated fatty acids with special emphasis on docosahexaenoic acid. J. Pharmacol. Sci., 2003, 92(4), 308-316.
[49]
Lombardo, Y.B.; Chicco, A.G. Effects of dietary polyunsaturated N-3 fatty acids on dyslipidemia and insulin resistance in rodents and humans. A review. J. Nutr. Biochem., 2006, 17(1), 1-13.
[50]
Sato, D.; Kusunoki, M.; Seino, N.; Nishina, A.; Feng, Z.; Tsutsumi, K.; Nakamura, T. Black soybean extract reduces fatty acid contents in subcutaneous, but not in visceral adipose triglyceride in high-fat fed rats. Int. J. Food Sci. Nutr., 2015, 66(5), 539-545.
[51]
Park, C.H.; Kim, J.H.; Lee, E.B.; Hur, W.; Kwon, O.J.; Park, H.J.; Yoon, S.K. Aronia melanocarpa extract ameliorates hepatic lipid metabolism through PPARγ2 downregulation. PLoS One, 2017, 12(1), e0169685.
[52]
Su, S.H.; Shyu, H.W.; Yeh, Y.T.; Chen, K.M.; Yeh, H.; Su, S.J. Caffeine inhibits adipogenic differentiation of primary adipose-derived stem cells and bone marrow stromal cells. Toxicol. Vitr., 2013, 27(6), 1830-1837.
[53]
Aoyagi, R.; Funakoshi-Tago, M.; Fujiwara, Y.; Tamura, H. Coffee inhibits adipocyte differentiation via inactivation of PPARγ. Biol. Pharm. Bull., 2014, 37(11), 1820-1825.
[54]
Kim, Y.J.; Choi, M.S.; Cha, B.Y.; Woo, J.T.; Park, Y.B.; Kim, S.R.; Jung, U.J. Long-term supplementation of honokiol and magnolol ameliorates body fat accumulation, insulin resistance, and adipose inflammation in high-fat fed mice. Mol. Nutr. Food Res., 2013, 57(11), 1988-1998.
[55]
Parray, H.A.; Lone, J.; Park, J.P.; Choi, J.W.; Yun, J.W. Magnolol promotes thermogenesis and attenuates oxidative stress in 3T3-L1 adipocytes. Nutrition, 2018, 50, 82-90.
[56]
Yang, J.Y.; Anne Della-Fera, M.; Nelson-Dooley, C.; Baile, C.A.; Yang, A. Anne Della-fera, M.; Nelson-dooley, C. Cellular and molecular molecular mechanisms of apoptosis induced by ajoene in 3T3-L1 adipocytes. Obesity, 2006, 14(3), 388-397.
[57]
Kandulska, K.; Nogowski, L.; Szkudelski, T. Effect of some phytoestrogens on metabolism of rat adipocytes. Reprod. Nutr. Dev., 1999, 39(4), 497-501.
[58]
Szkudelska, K.; Szkudelski, T.; Nogowski, L. Daidzein, coumestrol and zearalenone affect lipogenesis and lipolysis in rat adipocytes. Phytomedicine, 2002, 9(4), 338-345.
[59]
Povolo, C.; Foschini, A.; Ribaudo, G. Optimization of the extraction of bioactive molecules from Lycium barbarum fruits and evaluation of the antioxidant activity: A combined study. Nat. Prod. Res., 2018, 1-5.
[60]
Kang, M.H.; Park, W.J.; Choi, M.K. Anti-obesity and hypolipidemic effects of Lycium chinense leaf powder in obese rats. J. Med. Food, 2010, 13(4), 801-807.
[61]
Amagase, H.; Nance, D.M. Lycium barbarum increases caloric expenditure and decreases waist circumference in healthy overweight men and women: Pilot study. J. Am. Coll. Nutr., 2011, 30(5), 304-309.
[62]
Yu, H.M.; Chung, H.K.; Kim, K.S.; Lee, J.M.; Hong, J.H.; Park, K.S. PDE 5 inhibitor improves insulin sensitivity by enhancing mitochondrial function in adipocytes. Biochem. Biophys. Res. Commun., 2017, 493(1), 631-636.
[63]
Ghofrani, H.A.; Osterloh, I.H.; Grimminger, F. Sildenafil: From Angina to erectile dysfunction to pulmonary hypertension and beyond. Nat. Rev. Drug Discov., 2006, 5(8), 689-702.
[64]
Ribaudo, G.; Pagano, M.A.; Bova, S.; Zagotto, G. New therapeutic applications of Phosphodiesterase 5 Inhibitors (PDE5-Is). Curr. Med. Chem., 2016, 23(12), 1239-1249.
[65]
Mitschke, M.M.; Hoffmann, L.S.; Gnad, T.; Scholz, D.; Kruithoff, K.; Mayer, P.; Haas, B.; Sassmann, A.; Pfeifer, A.; Kilic, A. Increased cGMP promotes healthy expansion and browning of white adipose tissue. FASEB J., 2013, 27(4), 1621-1630.
[66]
Ribaudo, G.; Pagano, M.A.; Pavan, V.; Redaelli, M.; Zorzan, M.; Pezzani, R.; Mucignat-Caretta, C.; Vendrame, T.; Bova, S.; Zagotto, G. Semi-synthetic derivatives of natural isoflavones from Maclura pomifera as a novel class of PDE-5A inhibitors. Fitoterapia, 2015, 105, 132-138.
[67]
Ribaudo, G.; Vendrame, T.; Bova, S. Isoflavones from Maclura pomifera : Structural elucidation and in silico evaluation of their interaction with PDE5. Nat. Prod. Res., 2017, 31(17), 1988-1994.
[68]
Pavan, V.; Mucignat-Caretta, C.; Redaelli, M.; Ribaudo, G.; Zagotto, G. The old made new: Natural compounds against erectile dysfunction. Arch. Pharm. (Weinheim), 2015, 348(9), 607-614.
[69]
Wu, C.; Rajagopalan, S. Phosphodiesterase-4 inhibition as a therapeutic strategy for metabolic disorders. Obes. Rev., 2016, 17(5), 429-441.
[70]
Arnold, R.; Beer, D.; Bhalay, G.; Baettig, U.; Collingwood, S.P.; Craig, S.; Devereux, N.; Dunstan, A.; Glen, A.; Gomez, S. 8-Aryl xanthines potent inhibitors of phosphodiesterase 5. Bioorg. Med. Chem. Lett., 2002, 12(18), 2587-2590.
[71]
Hachem, R.; Assemat, G.; Martins, N.; Balayssac, S.; Gilard, V.; Martino, R.; Malet-Martino, M. Proton NMR for detection, identification and quantification of adulterants in 160 herbal food supplements marketed for weight loss. J. Pharm. Biomed. Anal., 2016, 124, 34-47.
[72]
Neves, D.B.; Caldas, E.D. Determination of caffeine and identification of undeclared substances in dietary supplements and caffeine dietary exposure assessment. Food Chem. Toxicol., 2017, 105, 194-202.
[73]
Patel, D.N.; Li, L.; Kee, C.L.; Ge, X.; Low, M.Y.; Koh, H.L. Screening of synthetic PDE-5 inhibitors and their analogues as adulterants: Analytical techniques and challenges. J. Pharm. Biomed. Anal., 2014, 87, 176-190.
[74]
Kitka, T.; Tuza, S.; Varga, B.; Horváth, C.; Kovács, P. Differential regulation of metabolic parameters by energy deficit and hunger. Metabolism, 2015, 64(10), 1235-1239.
[75]
Carvalho, L.M.; Cohen, P.A.; Silva, C.V.; Moreira, A.P.L.; Falcão, T.M.; Dal Molin, T.R.; Zemolin, G.; Martini, M. A new approach to determining pharmacologic adulteration of herbal weight loss products. Food Addit. Contam. Part A, 2012, 29(11), 1661-1667.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy