In vitro antihyperlipidemic potential of triterpenes from stem bark of Protorhus longifolia.
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.
Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, Republic of South Africa.
Rebamang A
RA
Mosa
Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, Republic of South Africa.
Javan J
JJ
Naidoo
Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, Republic of South Africa.
Fezile S
FS
Nkomo
Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, Republic of South Africa.
Sithandiwe E
SE
Mazibuko
Diabetes Discovery Platform, Medical Research Council (MRC), Tygerberg, South Africa.
Christo J F
CJ
Muller
Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, Republic of South Africa.
Andy R
AR
Opoku
D041721:3T3-L1 Cells / Q000187:drug effects; D027926:Anacardiaceae / Q000737:chemistry*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000737:chemistry* / Q000494:pharmacology*; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D002787:Sterol Esterase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
C000600532:3beta-hydroxylanosta-9,24-dien-21-oic acid; D001647:Bile Acids and Salts; D004791:Enzyme Inhibitors; D000960:Hypolipidemic Agents; D014315:Triterpenes; C000596161:methyl 3-hydroxylanosta-9,24-dien-21-oate; D007810:Lanosterol; D002787:Sterol Esterase; D005947:Glucose