Carvacrol ameliorates the progression of liver fibrosis through targeting of Hippo and TGF- signaling pathways in carbon tetrachloride (CCl4)-induced liver fibrosis in rats

Objective: Little is known about the exact underlying molecular mechanisms of the hepatoprotective effect of carvacrol against liver fibrosis. In the current study, we aimed to investigate the effect of carvacrol on the suppression of liver fibrosis progression via regulation of yes-associated protein (YAP) and transcriptional coactivators with a PDZ-binding motif (TAZ) and transforming growth factor beta (TGF-) pathway.Materials and methods: To fulfill our target, rats received carbon tetrachloride (CCl4) and carvacrol intraperitoneally, and orally, respectively for 10weeks. Body weight, liver weight, serum biochemical parameters, hepatic hydroxyproline content, and histological changes were determined. Furthermore, gene expression of collagen and key elements of Hippo and TGF- pathways were analyzed and then the protein levels of YAP, TAZ, and TGF- were detected in liver tissue.Results: Carvacrol administration normalized liver and body weight, serum biochemical parameters and hepatic hydroxyproline in CCl4 treated rats. Also, carvacrol downregulated TAZ and TGF- signaling pathway at transcriptional levels. Furthermore, carvacrol decreased hepatic protein levels of TGF-, TAZ, and YAP. Low expression of TAZ and YAP were accompanied with inhibition of TGF- signaling pathway.Conclusion: Our data clearly revealed that carvacrol suppresses the progression of liver fibrosis via targeting of TAZ, YAP, and TGF- signaling pathway.