Erchen Decoction regulates AMPK pathway in the treatment of metabolic syndrome induced by second-generation antipsychotics based on network analysis

Abstract

Abstract Background Erchen Decoction (ECD) has garnered clinical recognition for its efficacy in managing metabolic syndrome (MetS) induced by second-generation antipsychotics (SGAs). Despite its therapeutic success, the intricate pharmacological mechanisms underpinning ECD's action remain to be elucidated. Methods To predict protein interactions within the pharmacological framework of ECD, we constructed a protein-protein interaction (PPI) network using the shared targets between ECD components and MetS. Subsequently, we conducted Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on the common targets of ECD, SGAs, and MetS. A component-core target visualization network was developed for clearer representation. Molecular docking simulations were performed using Autodock Vina 1.2.0, and corroborative animal experiments were undertaken to validate ECD's mechanisms of action. Results Our research identified 221 potential targets of ECD, 1027 MetS-related targets, and 361 targets associated with clozapine and olanzapine. A PPI network was established from 79 intersecting targets of ECD and MetS. Analyses of 23 shared targets among ECD, SGAs, and MetS highlighted the AMPK pathway as potentially pivotal in the treatment of SGAs-induced MetS. The visualization network suggested ADRA1A, AHR, NR3C1, and SLC6A4 as core targets. In silico molecular docking revealed strong binding affinities of naringenin, baicalein, and quercetin in ECD with the NR3C1 and SLC6A4 targets. In vivo, ECD mitigated olanzapine-induced MetS in rats, accompanied by reduced expression of AMPK and SREBP1 in the liver. Conclusions Our findings propose that ECD may exert its therapeutic effects by targeting NR3C1 and SLC6A4 and modulating the AMPK pathway in the treatment of MetS induced by SGAs. These insights are in congruence with the results obtained from molecular docking and animal model studies.