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DOI: 10.1055/s-0034-1383262
In Vitro Antihyperlipidemic Potential of Triterpenes from Stem Bark of Protorhus longifolia
Publikationsverlauf
received 22. März 2014
revised 19. September 2014
accepted 12. Oktober 2014
Publikationsdatum:
11. November 2014 (online)
![](https://www.thieme-connect.de/media/plantamedica/201418/lookinside/thumbnails/10.1055-s-0034-1383262-1.jpg)
Abstract
Two lanostane triterpenes, 3β-hydroxylanosta-9,24-dien-21-oic acid (1) and methyl-3β-hydroxylanosta-9,24-dien-21-oate (2), were isolated from the stem bark of Protorhus longifolia. Their structures were deduced on the basis of spectroscopic analysis (NMR, HRMS, IR). This study investigated the in vitro anti-adipogenic activity of the two triterpenes. Their inhibitory activity was evaluated on selected lipid digestive enzymes (pancreatic lipase and cholesterol esterase). The inhibitory activity of the compounds on hormone-sensitive lipase and their ability to bind bile acids were also evaluated. The effect of the compounds on glucose uptake in C2C12 muscle cells and 3T3-L1 adipocytes, and on triglyceride accumulation in 3T3-L1 adipocytes was investigated. The triterpenes effectively inhibited the activities of the enzymes with IC50 values ranging from 0.04 to 0.31 mg/mL. The compounds showed a high affinity for secondary bile acids. Both compounds stimulated glucose uptake in C2C12 muscle cells and 3T3-L1 adipocytes. Compound 1 significantly reduced triglyceride accumulation in mature differentiated 3T3-L1 adipocytes. It is apparent that these lanostane triterpenes enhance glucose uptake and suppress adipogenesis, which together with their inhibitory effects on lipid digestive enzymes suggests that they have antihyperlipidemic potential.
Key words
Protorhus longifolia - Anacardiaceae - triterpenes - adipogenesis - antihyperlipidemic activity-
References
- 1 Chan RSM, Woo J. Prevention of overweight and obesity: how effective is the current public health approach. Int J Environ Res Public Health 2010; 7: 765-783
- 2 Greenberg AS, Obin MS. Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 2006; 83: 461S-465S
- 3 He Y, Li Y, Zhao T, Wang Y, Sun C. Ursolic acid inhibits adipogenesis in 3T3-L1 adipocytes through LKB1/AMPK pathway. PLoS ONE 2013; 8: e70135
- 4 Yun JW. Possible anti-obesity therapeutics from nature. Phytochemistry 2010; 71: 1625-1641
- 5 Chaput JP, St-Pierre S, Tremblay A. Currently available drugs for the treatment of obesity: sibutramine and orlistat. Mini Rev Med Chem 2007; 7: 3-10
- 6 Díaz EG, Folgueras TM. Systematic review of the clinical efficacy of sibutramine and orlistat in weigth loss, quality of life and its adverse effects in obese adolescents. Nutr Hosp 2011; 26: 451-457
- 7 Seo JB, Choe SS, Jeong HW, Park SW, Shin HJ, Choi SM, Park JY, Choi EW, Kim JB, Seen DS, Jeong JY, Lee TG. Anti-obesity effects of Lysimachia foenum-graecum characterized by decreased adipogenesis and regulated lipid metabolism. Exp Mol Med 2011; 43: 205-215
- 8 Sudhahar V, Kumar SA, Sudharsan PT, Varalakshmi P. Protective effect of lupeol and its ester on cardiac abnormalities in experimental hypercholesterolemia. Vasc Pharmacol 2007; 46: 412-418
- 9 Brown AW, Hang J, Dussault PH, Carr TP. Plant sterol and stanol substrate specificity of pancreatic cholesterol esterase. J Nutr Biochem 2010; 21: 736-740
- 10 Ghosh T, Maity TK, Singh J. Antihyperglycemic activity of bacosine, a triterpene from Bacopa monnieri, in alloxan-induced diabetic rats. Planta Med 2011; 77: 804-808
- 11 Liu J, Sun H, Wang X, Mu D, Liao H, Zhang L. Effects of oleanolic acid and maslinic acid on hyperlipidemia. Drug Dev Res 2007; 68: 261-266
- 12 Yadav VR, Prasad S, Sung B, Kannappan R, Aggarwal BB. Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer. Toxins 2010; 2: 2428-2466
- 13 Liu JJ, Toy WC, Liu S, Cheng A, Lim BK, Subramaniam T, Sum CF, Lim SC. Acetyl-keto-β-boswellic acid induces lipolysis in mature adipocytes. Biochem Biophys Res Commun 2013; 431: 192-196
- 14 Hutchings A, Scott AH, Lewis G, Cunningham A. Zulu medicinal Plants: an Inventory. Pietermaritzburg: University of Natal Press; 1996
- 15 Mosa RA, Lazarus GG, Gwala PE, Oyedeji AO, Opoku AR. In vitro anti-platelet aggregation, antioxidant and cytotoxic activity of extracts of some Zulu medicinal plants. J Nat Prod 2011; 4: 136-146
- 16 Mosa RA, Oyedeji OA, Shode FO, Singh M, Opoku AR. Triterpenes from the stem bark of Protorhus longifolia exhibit anti-platelet aggregation activity. Afr J Pharm Pharmacol 2011; 5: 2698-2714
- 17 Ahn JH, Liu Q, Lee C, Ahn MJ, Yoo HS, Hwang BY, Lee MK. A new pancreatic lipase inhibitor from Broussonetia kanzinoki . Bioorg Med Chem Lett 2012; 22: 2760-2763
- 18 Park CH, Chung BY, Lee SS, Bai HW, Cho JY, Jo C, Kim TH. Radiolytic transformation of rotenone with potential anti-adipogenic activity. Bioorg Med Chem Lett 2013; 23: 1099-1103
- 19 de Melo CL, Queiroz MG, Fonseca SG, Bizerra AM, Lemos TL, 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
- 20 Ali YB, Verger R, Carrière F, Petry S, Muller G, Abousalham A. The molecular mechanism of human hormone-sensitive lipase inhibition by substituted 3-phenyl-5-alkoxy-1,3,4-oxadiazol-2-ones. Biochimie 2012; 94: 137-145
- 21 Peterlik M. Role of bile acid secretion in human colorectal cancer. Wien Med Wochenschr 2008; 158: 539-541
- 22 Dibaise JK, Islam RS. Bile acids: an underrecognized and underappreciated cause of chronic diarrhea. In: Parrish CR, editor Practical gastroenterology. Nutrition issues in gastroenterology, Series 110. Westhampton Beach: Practical Gastroenterology Publishing; 2012
- 23 Liu Q, Ahn JH, Kim SB, Hwang BY, Lee MK. New phenolic compounds with anti-adipogenic activity from the aerial parts of Pulsatilla koreana . Planta Med 2012; 78: 1783-1786
- 24 Lee I, Kim H, Youn U, Kim J, Min B, Jung H, Na M, Hattori M, Bae K. Effect of lanostane triterpenes from the fruiting bodies of Ganoderma lucidum on adipocyte differentiation in 3T3-L1 cells. Planta Med 2010; 76: 1558-1563
- 25 Zeng XY, Zhou X, Xu J, Chan SMH, Xue CL, Molero JC, Ye JM. Screening for the efficacy on lipid accumulation in 3T3-L1 cells is an effective tool for the identification of new anti-diabetic compounds. Biochem Pharmacol 2012; 84: 830-837
- 26 Lee MS, Phuong TT. Stimulation of glucose uptake by triterpenoids from Weigela subsessilis . Phytother Res 2010; 24: 49-53
- 27 Yang MH, Avula B, Smillie T, Khan I, Khan SI. Screening of medicinal plants for PPARα and PPARγ activation and evaluation of their effects on glucose uptake and 3T3-L1 adipogenesis. Planta Med 2013; 79: 1084-1095
- 28 Bustanji Y, Issa A, Mohammad M, Hudaib M, Tawah K, Alkhatib H, Almasir I, Al-Khalid B. Inhibition of hormone sensitive lipase and pancreatic lipase by Rosmarinus officinalis extract and selected phenolic constituents. J Med Plants Res 2010; 4: 2235-2242
- 29 Machaba KE, Cobongella SZZ, Mosa RA, Lawal AO, Djarova TG, Opoku AR. In vivo anti-hyperlipidemic activity of the triterpene from the stem bark of Protorhus longifolia (Benrh) Engl. Lipids Health Dis 2014; 13: 131-137
- 30 Slanc P, Doljak B, Kreft S, Lunder M, Janeš D, Štrukelj B. Screening of selected food and medicinal plant extracts for pancreatic lipase inhibition. Phytother Res 2009; 23: 874-877
- 31 Morimoto C, Sumiyoshi M, Kameda K, Tsujita T, Okuda H. Relationship between hormone-sensitive lipolysis and lipase activity in rat fat cells. J Biochem 1999; 125: 976-981
- 32 Pietsch M, Gütschow M. Synthesis of tricyclic 1,3-oxazin-4-ones and kinetic analysis of cholesterol esterase and acetylcholinesterase inhibition. J Med Chem 2005; 48: 8270-8288
- 33 Matsumoto K, Kadowaki A, Ozaki N, Takenaka M, Ono H, Yokoyama S, Gato N. Bile acid-binding ability of Kaki-tannin from young fruits of Persimmon (Diospyros kaki) in vitro and in vivo . Phytother Res 2011; 25: 624-628
- 34 Dudhia Z, Louw J, Muller C, Joubert E, de Beer D, Kinnear C, Pheiffer C. Cyclopia maculata and Cyclopia subternata (honeybush tea) inhibits adipogenesis in 3T3-L1 pre-adipocytes. Phytomedicine 2013; 20: 401-408
- 35 Muller CJF, Joubert E, de Beer D, Sanderson M, Malherbe CJ, Fey SJ, Louw J. Acute assessment of an aspalathin-enriched green rooibos (Aspalathus linearis) extract with hypoglycemic potential. Phytomedicine 2012; 20: 32-39
- 36 Sanderson M, Mazibuko SE, Joubert E, de Beer D, Johnson R, Pheiffer C, Louw J, Muller CJF. Effects of fermented rooibos (Aspalathus linearis) on adipocyte differentiation. Phytomedicine 2014; 2: 109-117