Cynarin inhibits PDGF-BB-induced proliferation and activation in hepatic stellate cells through PPARγ

Abstract

Abstract Cynarin, a caffeoylquinic acid compound that was mainly extracted from Cynara scolymus L., displays various activities such as antioxidant, antibacterial, choleretic, and hepatoprotective functions. However, the target of cynarin and the mechanism of its hepatoprotective effect are still unclear. To find cynarin’s target, we performed molecular docking analysis, fluorescence-based ligand-binding assay, and reporter gene system assay. Our results indicated that cynarin was a partial agonist of peroxisome proliferator-activated receptor gamma (PPARγ). Further studies showed that cynarin significantly inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation and activation of rat CFSC-8G hepatic stellate cells (HSCs). Our results also revealed that cynarin inhibited PDGF-BB-induced extracellular regulated protein kinase (ERK) and v-akt murine thymoma viral oncogene homolog (AKT) phosphorylation in HSCs. In addition, this inhibition effect was PPARγ dependent since the knockdown of PPARγ significantly attenuated the effects of cynarin on PDGF-BB-induced p-ERK, p-AKT, and α-smooth muscle actin (α-SMA) expressions. Therefore, this study suggests that cynarin is a promising antifibrotic lead compound that inhibits the activation of HSCs, and it works by targeting PPARγ.