Cucurbitacin-B attenuates CCl 4 -induced hepatic fibrosis in mice through inhibition of STAT-3
Sallam, Alaliaa M.; Ahmed Esmat; Abdel-Naim, Ashraf B.;
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 CCl 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. CCl 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, 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 CCl 4 -induced liver fibrosis in mice. This can be attributed—at least partly—to inhibition of oxidative stress, inflammation and STAT3 signalling.
Other data
Title | Cucurbitacin-B attenuates CCl <inf>4</inf> -induced hepatic fibrosis in mice through inhibition of STAT-3 | Authors | Sallam, Alaliaa M.; Ahmed Esmat ; Abdel-Naim, Ashraf B. | Keywords | cucurbitacin-B;STAT-3;mice;liver;fibrosis | Issue Date | 1-Apr-2018 | Publisher | WILEY | Journal | Chemical Biology and Drug Design | ISSN | 17470277 | DOI | 10.1111/cbdd.13160 | PubMed ID | 29250925 | Scopus ID | 2-s2.0-85040614625 | Web of science ID | WOS:000427468300010 |
Recommend this item
Similar Items from Core Recommender Database
Items in Ain Shams Scholar are protected by copyright, with all rights reserved, unless otherwise indicated.