Kahweol decreases hepatic fibrosis by inhibiting the expression of connective tissue growth factor via the transforming growth factor-beta signaling pathway

Kahweol is a diterpene molecule found in Coffea Arabica beans. Previous studies have shown that coffee reduces liver fibrosis, but it is not clear which component of coffee has the protective effect. In this study, we examined whether kahweol has a protective effect on hepatic fibrosis in vivo and in vitro. Kahweol decreased hepatic fibrosis by inhibiting connective tissue growth factor (CTGF) expression in thioacetamide (TAA)-treated mice. The expression of phospho-Smad3, signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal protein kinase (JNK) increased in the livers of TAA-treated mice and decreased in the kahweol-treated group. Kahweol significantly decreased the expression of transforming growth factor beta (TGF-β)-stimulated type I collagen and CTGF expression in vitro. In addition, kahweol significantly decreased the expression of SMAD3, STAT3, ERK and JNK, which are involved in the induction of CTGF expression by TGF-β in hepatocytes, but not in HSCs. These results suggest that kahweol may be a new candidate for treatment of liver fibrosis.