title: Protopanaxatriol, a novel PPARγ antagonist from Panax ginseng, alleviates steatosis in mice.
abstract: Obesity is prevalent worldwide, and is highly associated with metabolic disorders, such as insulin resistance, hyperlipidemia and steatosis. Ginseng has been used as food and traditional herbal medicine for the treatment of various metabolic diseases. However, the molecular mechanisms how ginseng and its components participate in the regulation of lipogenesis are still largely unclear. Here, we identified that protopanaxatriol (PPT), a major ginseng constituent, inhibited rosiglitazone-supported adipocyte differentiation of 3T3-L1 cells by repressing the expression of lipogenesis-related gene expression. In high-fat diet-induced obesity (DIO) mice, PPT reduced body weight and serum lipid levels, improved insulin resistance, as well as morphology and lipid accumulation, particular macrovesicular steatosis, in the livers. These effects were confirmed with genetically obese ob/ob mice. A reporter gene assay showed that PPT specifically inhibited the transactivity of PPARγ, but not PPAR α, β/δ and LXR α, β. TR-FRET assay revealed that PPT was specifically bound to PPARγ LBD, which was further confirmed by the molecular docking study. Our data demonstrate that PPT is a novel PPARγ antagonist. The inhibition of PPARγ activity could be a promising therapy for obesity and steatosis. Our findings shed new light on the mechanism of ginseng in the treatment of metabolic syndrome.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Wujie
authors.initials: W
authors.lastname: Cai
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Fan
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.affiliation: Institutes of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004579:Electron Transport; D005234:Fatty Liver / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D012502:Sapogenins / Q000494:pharmacology*
chemical_list: D047495:PPAR gamma; D012502:Sapogenins; C081552:protopanaxatriol