Anti-fibrotic effects of brevilin A in hepatic fibrosis via inhibiting the STAT3 signaling pathway

Hepatic fibrosis is a chronic liver disease characterized by the accumulation of extracellular matrix (ECM). Activation of hepatic stellate cells (HSCs) after repetitive liver damage is a key event in hepatic fibrogenesis. As part of ongoing research projects to identify pharmacologically effective natural products, the phytochemical investigation of a MeOH extract of Centipeda minima led to the isolation of a sesquiterpene lactone, brevilin A, which was explored to elucidate potential anti-fibrotic effects by reversing HSC activation. First, we observed that transforming growth factor (TGF)-I31 treatment significantly increased the expression levels of HSC activation marker, ?-smooth muscle actin (?-SMA), and ECM protein such as collagen and fibronectin. Then, we demonstrated that brevilin A reversed the TGF-I31-induced increase in protein and mRNA expression levels of ?-SMA and collagen. To investigate the underlying molecular mechanism of brevilin A, we evaluated the effects of brevilin A on the STAT3 signaling pathway. STAT3 phosphorylation, increased by TGF-I31 treatment, was strongly inhibited by brevilin A; the expression levels of fibronectin and connective tissue growth factor were also significantly decreased by brevilin A. The present study indicated that brevilin A has a preventive and therapeutic potential against hepatic fibrosis.

Automated summary

The study found that brevilin A has a reversing effect on the expression levels of HSC activation marker α-SMA and ECM proteins induced by TGF-β1. Moreover, brevilin A inhibits STAT3 phosphorylation and decreases the expression levels of fibronectin and connective tissue growth factor induced by TGF-β1, indicating its potential in preventing and treating hepatic fibrosis.