title: Hypaphorine, an Indole Alkaloid Isolated from Caragana korshinskii Kom., Inhibites 3T3-L1 Adipocyte Differentiation and Improves Insulin Sensitivity in Vitro.
abstract: Obesity, a major health problem worldwide, is a complex multifactorial chronic disease that increases the risk for insulin resistance, type 2 diabetes, coronary heart disease, and hypertension. In this study, we assessed methods to isolate hypaphorine, a potent drug candidate for obesity and insulin resistance. Semi-preparative reversed-phase liquid chromatography (semi-preparative RPLC) was established as a method to separate three compounds, adenosine, l-tryptophan, and hypaphorine, from the crude extracts of Caragana korshinskii Kom. Due to its specific chemical structure, the effect of hypaphorine on differentiation and dexamethasone (DXM) induced insulin resistance of 3T3-L1 cells was investigated. The structures of the three compounds were confirmed by UV,1H-NMR, and13C-NMR analysis and compared with published data. The activity results indicated that hypaphorine prevented the differentiation of 3T3-L1 preadipocytes into adipocytes by down-regulating hormone-stimulated protein expression of peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (C/EBPα), and their downstream targets, sterol regulatory element binding protein 1 c (SREBP1c) and fatty acid synthase (FAS). Hypaphorine also alleviated DXM-induced insulin resistance in differentiated 3T3-L1 adipocytes via increasing the phosphorylation level of Akt2, a key protein in the insulin signaling pathway. Taken together, we suggest that the method can be applied to large-scale extraction and large-quantity preparation of hypaphorine for treatment of obesity and insulin resistance.
authors.affiliation: Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, 23 Xin'ning Road, Xining, 810008, P. R. China.|University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
authors.forename: Guangxiang
authors.initials: G
authors.lastname: Luan
authors.affiliation: Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, 23 Xin'ning Road, Xining, 810008, P. R. China.|University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Tie
authors.affiliation: Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, 23 Xin'ning Road, Xining, 810008, P. R. China.|University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, 23 Xin'ning Road, Xining, 810008, P. R. China.|Center of Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, 30 Qingquan Road, Yantai, 264005, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Center of Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, 30 Qingquan Road, Yantai, 264005, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: Center of Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, 30 Qingquan Road, Yantai, 264005, P. R. China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, 23 Xin'ning Road, Xining, 810008, P. R. China.|State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, 810008, P. R. China.
authors.forename: Honglun
authors.initials: H
authors.lastname: Wang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D032602:Caragana / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D026121:Indole Alkaloids / Q000302:isolation & purification / Q000494:pharmacology; D007211:Indoles / Q000302:isolation & purification / Q000494:pharmacology*; D007333:Insulin Resistance; D051379:Mice; D009765:Obesity / Q000188:drug therapy; D010936:Plant Extracts / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D026121:Indole Alkaloids; D007211:Indoles; D010936:Plant Extracts; C001529:lenticin
keywords: 3T3-L1 cells; Adipocyte differentiation; Hypaphorine; Insulin resistance; Isolation