Hypaphorine,an Indole Alkaloid Isolated from Caragana korshinskii Kom., Inhibites 3T3‐L1 Adipocyte Differentiation and Improves Insulin Sensitivity in Vitro

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, and ¹³C‐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.