Berberine alleviates liver fibrosis via inhibition of the PI3K/Akt/NF-κB signaling pathway in rats
Abstract: Fibrosis is the most important pathological feature of chronic liver disease, and it is also an early step in the progression of chronic hepatitis and cirrhosis, eventually developing into hepatocellular carcinoma (HCC). In present study, we aimed at elucidating the therapeutic effects of inhibiting PI3K/Akt/NF-κB signaling pathway in rat hepatic fibrosis by using berberine, an isoquinoline alkaloid which is known for its therapeutic effect on inflammation, diabetes, hyperlipidemia and tumor. A model of hepatic fibrosis was established in SD rats by intraperitoneal injection of thioacetamide, and explored the effect of berberine in the treatment of liver fibrosis. hematoxylin-eosin and sirius red staining were examined to determine histo- pathological changes in liver fibrosis. Immunohistochemical staining (IHC) were used to examine the relative levels of α‑smooth muscle actin (α-SMA) and collagen type I in the liver of rats. In addition, the relative protein expression levels of PI3K/Akt/NF-κB signaling pathway were measured by western blotting, and the relative levels of ALT, Hyp and liver index in groups were evaluated. We observed a massive increase of the relative levels of α‑smooth muscle actin (α-SMA) and collagen type I in the liver of thioacetamide-induced rats compared with the normal group, whereas berberine treatment reversed these changes. The relative levels of ALT, Hyp and liver index in the berberine-treated group were significantly lower than those in the model rats with injection of thioacetamide. Importantly, we demonstrated that berberine could reverse thioacetamide-induced liver fibrosis through the PI3K/Akt/NF-κB pathway in vivo. In conclusion, berberine is believed to have a therapeutic effect in treatment with hepatic fibrosis, probably by inhibiting the PI3K/Akt/NF-κB signaling pathway in rats.
Key words: berberine, liver fibrosis, signaling pathway