A novel Gynostemma pentaphyllum saponin and its adipogenesis inhibitory effect through modulating Wnt/β-catenin pathway and cell cycle in mitotic clonal expansion

A novel saponin (JS) was isolated from the tetraploid jiaogulan, a popular tea also known as Gynostemma pentaphyllum, and characterized for its chemical structure. JS was investigated for its inhibitory effect on adipocyte differentiation and the potential molecular mechanisms using 3T3-L1 murine pre-adipocytes. JS treatment down-regulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) at both mRNA and protein levels. Further analysis proved that the inhibition was primarily limited to the early stage of adipocyte differentiation, where JS decreased the DNA-binding activity of C/EBPβ by blocking its phosphorylation. In addition, JS increased phosphorylation of glycogen synthase kinase 3β (GSK-3β) and subsequently increased stability and nuclear translocation of β-catenin through modulating expression of Wnt/β-catenin signaling components. Moreover, JS-induced down regulation of adipogenic markers and fat accumulation is β-catenin-dependent. These data suggested that this novel saponin compound might inhibit adipogenesis through activating Wnt/β-catenin signaling during adipocyte differentiation.