Protective effects of catalpol on mitochondria of hepatocytes in cholestatic liver injury

Cholestasis, which is caused by the obstruction of bile flow, can lead to rapid organ injury, cell apoptosis and necrosis of hepatocytes, and may eventually develop into fibrosis and cirrhosis. Oxidative stress and mitochondrial dysfunction are the key pathogenic signs of hepatic cholestasis. Catalpol has pharmacological activities, including antioxidative and anti-inflammatory effects, and may relieve mitochondrial damage and restore mitochondrial membrane potential. However, the potential roles and mechanisms of catalpol in cholestasis-induced liver injury are not clear. In the present study, liver function-related indexes were measured in the serum of mice by commercial kits. In addition, levels of serum inflammatory factors were detected by ELISA. Hematoxylin and eosin staining was performed to observe histopathological changes, and mitochondrial membrane potential was detected using JC-1 staining. Mitochondrial adenosine triphosphate (ATP), reactive oxygen species (ROS) and malondialdehyde levels were determined using a luciferase reporter kit, flow cytometry and a thiobarbituric acid reactive substance assay kit, respectively. Western blotting was performed to detect the expression levels of apoptosis-related proteins in liver tissues. The findings revealed that catalpol reduced liver damage caused by cholestasis, improved the mitochondrial membrane potential, and increased the ATP content and glutathione content of cholestasis model mice. Moreover, catalpol also reduced the ROS level, inhibited lipid peroxidation, and regulated oxidative stress and apoptotic protein expression. Thus, the present study preliminarily confirmed that catalpol can reduce liver injury in a mouse model of cholestasis through inhibiting oxidative stress and enhancing mitochondrial membrane potential.