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.

Berberine and Its Study as an Antidiabetic Compound

“…The results also showed that berberine has a higher affinity value compared to the native ligand of the PPARG complex (PDB ID:1I7I), with a binding energy value of berberine-PPARG of −8.4 kcal/mol and a binding energy value of ligand-PPARG of −7.6 kcal/mol. These results indicate that berberine compounds have binding potential toward PPARG [57].…”

In Silico Exploration of Berberine as a Potential Wound Healing Agent via Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

“…The network analysis conducted has unveiled a complex web of interactions and pathways that illuminate role of berberine in the process of wound healing. Huang et al in their recent publication, reported the network pharmacology-based apprach and identified some key molecualr targets for berberine [47]. Molecular docking study also reported in their work [47].…”

“…Huang et al in their recent publication, reported the network pharmacology-based apprach and identified some key molecualr targets for berberine [47]. Molecular docking study also reported in their work [47]. Berberine, a naturally occurring isoquinoline alkaloid, has been gaining attention for its potential therapeutic properties, including wound healing.…”

“…The assessment of the resulting docked complexes was based on the consideration of lowest energy values (Kcal/mol) and the examination of bonding patterns, encompassing hydrogen, hydrophobic, and electrostatic interactions. Huang et al in their recent publication, reported the docking study of berberine and found the promising binding energy of berberine against PDB Ids including 1O43, 1I7I, 1NHZ, 5JQH, 5WIU, 2BK4, 3QM4, and 2ILT [47].…”