Multi-Bioinformatics Approach Reveals COX5B-Mediated Modulation of Oxidative Phosphorylation and ROS Levels by Water and Ethanol Extracts of Schisandrae Fructus in SW1783 Cells.

Schisandrae Fructus is a traditional medicinal herb used to suppress hyperactivity and exhibits a wide range of therapeutic effects and few side effects; however, the molecular mechanism of action engaged by the multiple compounds found within Schisandrae Fructus remains insufficiently studied. Herein, we aimed to confirm the inhibition of oxidative phosphorylation by hot water and ethanol extracts of Schisandrae Fructus and determine the activity and pathways affected by each extract. To refine target prediction, centrality analysis was performed using drug-target interactions, protein-protein interactions, and integrated networks. Our analyses revealed that oxidative phosphorylation was inhibited in the water extract, and COX5B was predicted to be a common target. Centrality analysis revealed COX5B's high score, suggesting its role as an efficient mediator of oxidative phosphorylation regulation. In vitro analysis confirmed that COX5B expression, oxidative phosphorylation activity and reactive oxygen species levels were suppressed by the water extract. The water and ethanol extracts of Schisandrae Fructus differentially affected oxidative phosphorylation activity. COX5B, a key target regulated by the water extract of Schisandrae Fructus, emerged as a potential biomarker. These findings suggest that COX5B-mediated oxidative phosphorylation modulation may serve as a key mechanism underlying the anticancer and antiaging effects of Schisandrae Fructus.