Network Pharmacology and Molecular Docking Analysis on Targets and Mechanisms of Berberine in Atypical Antipsychotic-Induced Metabolic Syndrome

Abstract

Berberine (BBR), an isoquinoline alkaloid, possesses multiply pharmacological effects as a potential therapeutic drug for antipsychotic-induced metabolic syndrome (MetS). However, the underlying therapeutic mechanisms have not been fully elucidated. In this study, we aim to investigate the possible mechanisms by identifying the key targets and biological pathways through network pharmacology and molecular docking analysis. A total of 23 overlapping targets in the intersection set among BBR, atypical antipsychotic drugs (AADs), and MetS were determined. PPI network analysis showed that 22 out of the 23 overlapping targets closely interacted with the others. The following pathway enrichment analysis and molecular docking indicated a central role of peroxisome proliferator-activated receptor-γ (PPARG) as the key target of BBR against AAD-induced MetS by acting on the PPAR signaling pathway, lipid and atherosclerosis, and AMP activated protein kinase (AMPK) signaling pathway. In addition, cytochrome P-450 2D6 (CYP2D6) could be considered as another target of BBR in ameliorating antipsychotic-induced metabolic side effects. Collectively, this study investigated the central targets and biological pathways of BBR against AAD-induced MetS from a systematic perspective, and thus brings novel insights into further understanding of the protective effects of BBR.