Anti-obesity Effects of Physalin A through Regulation of Lipid Metabolism and Nrf2 Pathway

Abstract

Physalin A (PA) has been reported for various pharmacological properties including antioxidant, apoptosis and anti-inflammation activities. Especially, our previous study showed that PA exerts cancer chemoprevention through upregulation of Nrf2(Nuclear factor erythroid 2-related factor 2) pathway. In this study we aimed to examine the relationship between lipid metabolism and Nrf2 pathway of PA in 3T3-L1 and palmitic acid-induced (PMI) HepG2 cells. First of all, when the TG content and lipid accumulation were measured by TG assay and Oil red O staining in 3T3-L1 cells, both TG content and lipid accumulation were clearly decreased. As observed by western blotting and qRT-PCR analysis, PA treatment decreased adipogenesis-related gene and regulated lipid metabolism-related genes in 3T3-L1 cells. To confirm whether physalin A activates antioxidant response element (ARE) by enhancing Nrf2 binding, we conducted reporter gene assay and observed that ARE activity was dose-dependently increased by PA in ARE expressing HepG2 stable cells. Furthermore, we observed that PA increased the expression of Nrf2 and its target genes as well as lipid metabolism related genes in PMI-HepG2 cells. Taken together, these results may suggest that PA exerts anti-obesity effects by crosstalk in regulation of lipid metabolisn and Nrf2 pathway.