Mulberry fruit extract prevents liver fibrosis via inhibition of inflammation in DEN-treated rats

Liver disease, which involves an extensive range of liver pathologies from fatty liver to hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, is a serious health problem around the world. Mulberry fruits are rich in polyphenols and have been reported to remove free radicals and mitigate inflammation in the presence of gastric cancer, melanoma, leukemia, or liver injury induced by alcohol or carbon tetrachloride (CCl_4). Our previous results have demonstrated the beneficial effects of mulberry water extract (MWE) on hepatocarcinogenesis via phosphoinositide 3-kinase (PI3K)/phosphorylated protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) inhibition and cell death-related proteins. The purpose of this study was to assess the anti-inflammatory effect of MWE on liver cancer-related fibrosis in diethylnitrosamine (DEN)-induced rats. Oral treatment with different concentrations of MWE reduced α-smooth muscle actin (α-SMA, fibrosis marker) in DEN-induced rats. Compared with the DEN-induced group, MWE significantly increased anti-oxidative enzyme activities. Rats receiving MWE supplementation showed reduced interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels compared to untreated DEN-induced rats. Inflammatory and fibrotic proteins such as collagen IV, fibronectin, phosphorylated signal transducer and activator of transcription (STAT)3, PI3K, Akt, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were also inhibited by MWE treatment in DEN-induced rats. These results indicated that MWE is a potential health supplement for preventing liver fibrosis and hepatocarcinogenesis.