Cucurbitacin‐B attenuates CC l 4 ‐induced hepatic fibrosis in mice through inhibition of STAT ‐3

Liver fibrosis is a major health concern worldwide. Inhibitors of Signal Transducer and Activator of Transcription 3 ( STAT 3) have been reported to attenuate experimental liver fibrosis. Therefore, the aim of this study was to investigate the potential ameliorative effect of cucurbitacin‐B (Cucu‐B) against CC l 4 ‐induced liver fibrosis in mice. Treatment with Cucu‐B (5 mg/kg) preserved hepatocellular membrane integrity and amended the metabolic function as indicated by preventing the rise of serum liver function markers. This was confirmed histologically. CC l 4 ‐induced oxidative stress was improved by Cucu‐B treatment (1 and 5 mg/kg). Furthermore, Cucu‐B treatment ameliorated the fibrotic state as evidenced by inhibiting the rise of hydroxyproline liver content and mitigating the overexpressions of collagen‐1α, α‐smooth muscle actin (α‐ SMA ) and transforming growth factor beta ( TGF ‐β) as well as the downexpression of matrix metalloproteinase‐2 ( MMP ‐2) mRNA . Importantly, STAT 3 activity was inhibited by Cucu‐B as confirmed by decreased phosphorylation of STAT 3 without changing total STAT 3 expression. This was substantiated by the reduced Bcl‐2 together with increased Bax mRNA expressions with subsequent elevation of Bax/Bcl‐2 ratio. In conclusion, Cucu‐B hampers CC l 4 ‐induced liver fibrosis in mice. This can be attributed—at least partly—to inhibition of oxidative stress, inflammation and STAT 3 signalling.