Boldine protects against carbon tetrachloride-induced chronic liver injury by regulating NF-κB signaling pathway

Sustained liver injuries predominantly promote oxidative stress and inflammation that lead to the progression of chronic liver disease (CLD), including fibrosis, cirrhosis, and hepatocellular carcinoma. Boldine, an alkaloid isolated from Peumus boldus, has been shown to have antioxidant and anti-inflammatory effects. Currently, there is no definitive treatment option available for CLD. Therefore, we investigated the hepatoprotective effect of boldine against carbon tetrachloride (CCl4)-induced chronic liver injury in rats. CCl4 (2 mL/kg., b.w., i.p.) was administered twice weekly for 5 weeks to induce chronic liver injury in rats. Separate groups of rats were given boldine (20 mg/kg b.w., and 40 mg/kg b.w.) and silymarin (100 mg/kg b.w.) orally, daily. Serum transaminases, lipid peroxidation, and antioxidant levels were measured, and nuclear factor-kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (cox-2), interleukin-1 beta (IL-1 beta), and alpha-smooth muscle actin (alpha-SMA) gene and protein expressions were evaluated. CCl4 administration increased liver marker enzymes of hepatotoxicity in serum and oxidative stress markers, inflammatory genes and alpha-smooth muscle actin expression in liver tissue. Boldine concurrent treatment suppressed CCl4-induced elevation of transaminase levels in serum, restored enzymic and non-enzymic antioxidants, and downregulated NF-kappa B, TNF-alpha, Cox-2 and IL-1 beta expressions, thereby suppressing hepatic inflammation. Boldine administration also repressed alpha-SMA expression. The results of this study demonstrate the antioxidant, anti-inflammatory, and antifibrotic properties of boldine, and it can be a potential therapeutic candidate in the treatment of CLD. Boldine, an alkaloid isolated from Peumus boldus, has been previously shown to have antioxidant effects. This study provides evidence that boldine is beneficial in preventing carbon tetrachloride-induced chronic liver injury in rats due to its antioxidant, anti-inflammatory and antifibrotic potential. image