Subscribe to RSS
DOI: 10.1055/s-0042-114222
Amyrins from Protium heptaphyllum Reduce High-Fat Diet-Induced Obesity in Mice via Modulation of Enzymatic, Hormonal And Inflammatory Responses
Publication History
received 08 April 2016
revised 15 July 2016
accepted 29 July 2016
Publication Date:
15 August 2016 (online)
Abstract
Obesity remains a global problem. In search of phytochemicals that have antiobesity potential, this study evaluated α,β-amyrin, a triterpenoid mixture from Protium heptaphyllum, on high-fat diet-induced obesity in mice. Groups of mice (n = 8) were fed a normal diet or a high-fat diet, and were orally treated or not treated with either α,β-amyrin (10 or 20 mg/kg) or sibutramine (10 mg/kg) for 15 weeks. Variables measured at termination were body weight, visceral fat accumulation, adipocyte surface area, peroxisome proliferator-activated receptor gamma, and lipoprotein lipase expressions in adipose tissue, the levels of plasma glucose and insulin, the satiety hormones ghrelin and leptin, the digestive enzymes amylase and lipase, and the inflammatory mediators TNF-α, interleukin-6, and MCP-1. Results showed that α,β-amyrin treatment resulted in lower high-fat diet-induced increases in body weight, visceral fat content, adipocyte surface area, peroxisome proliferator-activated receptor gamma, and lipoprotein lipase expressions, and blood glucose and insulin levels. Additionally, the markedly elevated leptin and decreased ghrelin levels seen in the high-fat diet-fed control mice were significantly modulated by α,β-amyrin treatment. Furthermore, α,β-amyrin decreased serum TNF-α and MCP-1. These results suggest that α,β-amyrin could be beneficial in reducing high-fat diet-induced obesity and associated disorders via modulation of enzymatic, hormonal, and inflammatory responses.
-
References
- 1 Ling H, Lenz TL, Burns TL, Hilleman DE. Reducing the risk of obesity: defining the role of weight loss drugs. Pharmacotherapy 2013; 33: 1308-1321
- 2 Shin JH, Gadde KM. Clinical utility of phentermine/topiramate (Qsymia™) combination for the treatment of obesity. Diabetes Metab Syndr Obes 2013; 6: 131-139
- 3 Sumithran P, Proietto J. Benefit-risk assessment of orlistat in the treatment of obesity. Drug Saf 2014; 37: 597-608
- 4 Gooda Sahib N, Saari N, Ismail A, Khatib A, Mahomoodally F, Abdul Hamid A. Plantsʼ metabolites as potential antiobesity agents. Sci World J 2012; 2012: 1-8
- 5 Wong CP, Kaneda T, Morita H. Plant natural products as an anti-lipid droplets accumulation agent. J Nat Med 2014; 68: 253-266
- 6 Chiesi M, Huppertz C, Hofbauer KG. Pharmacotherapy of obesity: targets and perspectives. Trends Pharmacol Sci 2001; 22: 247-254
- 7 Yun JW. Possible anti-obesity therapeutics from nature – a review. Phytochemistry 2010; 71: 1625-1641
- 8 Rebello C, Greenway FL, Dhurandhar NV. Functional foods to promote weight loss and satiety. Curr Opin Clin Nutr Metab Care 2014; 17: 596-604
- 9 Nazaruk J, Borzym-Kluczyk M. The role of triterpenes in the management of diabetes mellitus and its complications. Phytochem Rev 2014; 14: 675-690
- 10 Vieira-Júnior GM, de Souza CML, Chaves MH. Resina de Protium heptaphyllum: isolamento, caracterização estrutural e avaliação das propriedades térmicas. Quim Nova 2005; 28: 183-187
- 11 Siani AC, Nakamura MJ, Tappin MRR, Monteiro SS, Guimarães AC, Ramos MFS. Chemical composition of south american Burseraceae non-volatile oleoresins and preliminary solubility assessment of their commercial blend. Phytochem Anal 2012; 23: 529-539
- 12 Jäger S, Trojan H, Kopp T, Laszczyk MN, Scheffler A. Pentacyclic triterpene distribution in various plants – rich sources for a new group of multi-potent plant extracts. Molecules 2009; 14: 2016-2031
- 13 Sheng H, Sun H. Synthesis, biology and clinical significance of pentacyclic triterpenes: a multi-target approach to prevention and treatment of metabolic and vascular diseases. Nat Prod Rep 2011; 28: 543
- 14 Oliveira FA, Vieira-Júnior GM, Chaves MH, Almeida FR, Santos KA, Martins FS, Silva RM, Santos FA, Rao VS. Gastroprotective effect of the mixture of α- and β-amyrin from Protium heptaphyllum: role of capsaicin-sensitive primary afferent neurons. Planta Med 2004; 70: 780-782
- 15 Oliveira FA, Chaves MH, Almeida FRC, Lima RCP, Silva RM, Maia JL, Brito GAAC, Santos FA, Rao VS. Protective effect of α- and β-amyrin, a triterpene mixture from Protium heptaphyllum (Aubl.) March. trunk wood resin, against acetaminophen-induced liver injury in mice. J Ethnopharmacol 2005; 98: 103-108
- 16 Otuki MF, Ferreira J, Lima FV, Meyre-Silva C, Muller LA, Cani GS, Santos ARS, Yunes RA. Antinociceptive properties of mixture of α-amyrin and β-amyrin triterpenes: evidence for participation of protein kinase C and protein kinase A pathways. J Pharmacol Exp Ther 2005; 313: 310-318
- 17 Bandeira PN, Fonseca AM, Costa SMO, Lins MUDS, Pessoa ODL, Monte FJQ, Nogueira NAP, Lemos TLG. Antimicrobial and antioxidant activities of the essential oil of resin of Protium heptaphyllum . Nat Prod Comm 2006; 1: 117-120
- 18 Vitor C, Figueiredo C, Hara D, Bento A, Mazzuco T, Calixto J. Therapeutic action and underlying mechanisms of a combination of two pentacyclic triterpenes, α- and β-amyrin, in a mouse model of colitis. Br J Pharmacol 2009; 157: 1034-1044
- 19 Santos FA, Frota JT, Arruda BR, de Melo TS, da Silva AA, Brito GA, Chaves MH, Rao VS. Antihyperglycemic and hypolipidemic effects of α, β-amyrin, a triterpenoid mixture from Protium heptaphyllum in mice. Lipids Health Dis 2012; 11: 98
- 20 de Melo CL, Queiroz MGR, Fonseca SGC, Bizerra AMC, Lemos TLG, Melo TS, Santos FA, Rao VS. Oleanolic acid, a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet. Chem Biol Interact 2010; 185: 59-65
- 21 Rao VS, de Melo CL, Queiroz MGR, Lemos TLG, Menezes DB, Melo TS, Santos FA. Ursolic acid, a pentacyclic triterpene from Sambucus australis, prevents abdominal adiposity in mice fed a high-fat diet. J Med Food 2011; 14: 1375-1382
- 22 Ghibaudi L, Cook J, Farley C, van Heek M, Hwa JJ. Fat intake affects adiposity, comorbidity factors, and energy metabolism of sprague-dawley rats. Obes Res 2002; 10: 956-963
- 23 Urs S, Henderson T, Le P, Rosen CJ, Liaw L. Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction. Br J Nutr 2012; 108: 1025-1033
- 24 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: 21-34
- 25 Handjieva-Darlenska T, Boyadjieva N. The effect of high-fat diet on plasma ghrelin and leptin levels in rats. J Physiol Biochem 2009; 65: 157-164
- 26 Iyer A, Fairlie DP, Prins JB, Hammock BD, Brown L. Inflammatory lipid mediators in adipocyte function and obesity. Nat Rev Endocrinol 2010; 6: 71-82
- 27 Greenberg AS, Obin MS. Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 2006; 83: 461-465
- 28 Wang H, Eckel RH. Lipoprotein lipase: from gene to obesity. AJP Endocrinol Metab 2009; 297: E271-E288
- 29 Corzo C, Griffin PR. Targeting the peroxisome proliferator-activated receptor-γ to counter the inflammatory milieu in obesity. Diabetes Metab J 2013; 37: 395-403
- 30 Alkhouri N, Gornicka A, Berk MP, Thapaliya S, Dixon LJ, Kashyap S, Schauer PR, Feldstein AE. Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J Biol Chem 2010; 285: 3428-3438
- 31 Arterburn DE, Crane PK, Veenstra DL. The efficacy and safety of sibutramine for weight loss: a systematic review. Arch Intern Med 2004; 164: 994-1003
- 32 Scheen AJ. Sibutramine on cardiovascular outcome. Diabetes Care 2011; 34: S114-S119
- 33 Yim DS, Han S, Jeon S, Hong T, Lee J, Bae SH, Park W, Park G, Youn S, Jang DY, Kim KS. Exposure-response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development. Drug Des Devel Ther 2015; 9: 5185-5194
- 34 Olea RSG, Roque NF. Análise de misturas de triterpenos por RMN de 13 C. Quim Nova 1990; 13: 278-281
- 35 Mahato SB, Kundu AP. 13 C NMR Spectra of pentacyclic triterpenoids – a compilation and some salient features. Phytochemistry 1994; 37: 1517-1575
- 36 Estadella D, Oyama LM, Dâmaso AR, Ribeiro EB, Oller Do Nascimento CM. Effect of palatable hyperlipidic diet on lipid metabolism of sedentary and exercised rats. Nutrition 2004; 20: 218-224
- 37 Santos FA, Rao VS, Carvalho KMMB, Morais TC, da Silva AACA, Chaves MH. The alpha, beta-amyrin from Protium heptaphyllum exerts antiobese-related effects in mice fed on high fat diet. Planta Med 2013; 79: PE14
- 38 Folch J, Lees M, Sloane Stanley G. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1987; 55: 999-1033
- 39 Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001; 29: e45