Cucurbitacin-B attenuates CCl4-induced hepatic fibrosis in mice through inhibition of STAT-3

Abstract

Liver fibrosis is a major health concern worldwide. Inhibitors of Signal Transducer and Activator of Transcription 3 (STAT3) have been reported to attenuate experimental liver fibrosis. Therefore, the aim of current study was to investigate the potential ameliorative effect of cucurbitacin-B (Cucu-B) against CCl₄-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. CCl₄-induced oxidative stress was improved by Cucu-B treatment (1 & 5 mg/kg). Further, 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, STAT3 activity was inhibited by Cucu-B as confirmed by decreased phosphorylation of STAT3 without changing total STAT3 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 CCl₄-induced liver fibrosis in mice. This can be attributed – at least partly – to inhibition of oxidative stress, inflammation and STAT3 signaling.

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Cucurbitacin-B protected against CCl₄-induced liver injury and fibrosis in mice. This was confirmed histologically and biochemically. Fibrosis-related markers were also improved by cucurbitacin-B treatment. These actions can be attributed, at least partly, to inhibition of oxidative stress, inflammation and STAT3 signaling.

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