Oxyberberine suppressed the carbon tetrachloride-induced liver fibrosis by inhibiting liver inflammation in a sirtuin 3-dependent manner in mice.

Previous studies have shown that oxyberberine (OBB), a novel gut microbiota metabolite of berberine, exhibited prominent protective property against acute liver injury and non-alcoholic fatty liver diseases, however, the effect of OBB on liver fibrosis and its potential mechanisms remain largely unknown. This study was aimed to study the effects of OBB on carbon tetrachloride (CCl)-induced liver fibrosis and tried to clarify the potential mechanisms by focusing on regulating of sirtuin 3 (SIRT3)-mediated liver inflammation. OBB significantly alleviated the liver injury and fibrosis in CCl-treated C57/BL6 mouse livers. OBB evidently down-regulated the expression of inflammatory factors and reduced the levels of inflammatory factors in CCl-treated mouse livers. Noteworthy, CCl-treated decreased the mRNA and protein expression of SIRT3, and treatment with OBB notably increased the expression of SIRT3 both in transcriptional and translational levels in CCl-treated mice livers. OBB also suppressed the cell viability of TGF-β1-stimulated JS-1 cells and inhibited the protein expression of α-SMA but increased the expression of SIRT3 in stimulated JS-1 cells. Moreover, depletion of SIRT3 weakened the anti-inflammatory effects of OBB in stimulated JS-1 cells. Interestingly, the anti-liver injury and anti-fibrotic effects of OBB could be available in CCl-treated WT (129S1/SvImJ) mice but were unavailable in CCl-treated SIRT3 knockout (KO) mice. In addition, the anti-inflammatory effect of OBB was only found in CCl-treated WT mice but was not in SIRT3 KO mice. Collectively, these findings suggested that OBB suppressed the liver injury and fibrosis through inhibition of liver inflammation in a SIRT3-dependent manner in CCl-treated mice.