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

Cucurbitacin‐B attenuates CCl4‐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 (STAT3) 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 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 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, 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 signalling. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Chemical Biology & Drug Design Wiley

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

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
Copyright © 2018 John Wiley & Sons A/S
ISSN
1747-0277
eISSN
1747-0285
D.O.I.
10.1111/cbdd.13160
Publisher site
See Article on Publisher Site

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 this 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 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, 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 signalling.

Journal

Chemical Biology & Drug DesignWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

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