Evaluating the protective effects of individual or combined ginsenoside compound K and the downregulation of soluble epoxide hydrolase expression against sodium valproate-induced liver cell damage.

Sodium valproate (SVP) is one of the most commonly prescribed antiepileptic drugs. However, SVP is known to induce hepatotoxicity, which limits its clinical application for treating various neurological disorders. Previously, we found that ginsenoside compound K (G-CK) demonstrated protective effects against SVP-induced hepatotoxicity by mitigating oxidative stress and mitochondrial damage, as well as downregulating the expression of soluble epoxide hydrolase (sEH) in rats. This study aimed to assess the effect of G-CK on SVP-induced cytotoxicity in human hepatocytes (L02 cell line), as well as the effect of the downregulation of sEH expression on both the hepatotoxicity of SVP and the hepatoprotective effects of G-CK. We observed that G-CK significantly ameliorated the decrease of cell viability, elevated ALT, AST and ALP activities, significant oxidative stress, and loss of mitochondrial membrane potential induced by SVP in L02 cells. G-CK also inhibited the SVP-mediated upregulation of sEH expression. Transfection of the L02 cells with siRNA-sEH led to a partial improvement in the L02 cytotoxicity caused by SVP by mitigating cellular oxidative stress without recovering the reduced mitochondrial membrane potential. Furthermore, the combination of siRNA-sEH and G-CK had better inhibitory effects on the SVP-induced changes of all detection indices except mitochondrial membrane potential than G-CK alone. Together, our results demonstrated that the combination of siRNA-sEH and G-CK better suppressed the SVP-induced cytotoxicity in L02 cells compared to either G-CK or siRNA-sEH alone.