Exploring the Therapeutic Mechanism of Pingxin Dingzhi Decoction Through Network Pharmacology and Molecular Docking

Alpha Psychiatry. 2024 Sep 1;25(5):584-591. doi: 10.5152/alphapsychiatry.2024.241642. eCollection 2024 Sep.

Abstract

Objective: Studies have demonstrated that the combination of antipsychotics and Pingxin Dingzhi Decoction (PXDZD) can effectively enhance treatment efficacy for schizophrenia (SCZ), while simultaneously reducing the adverse reactions associated with antipsychotic treatment. However, the exact mechanism by which PXDZD exerts its therapeutic effects is still unknown. The aim of this study is to investigate the action mechanism of PXDZD using network pharmacology and molecular docking techniques.

Methods: The primary components and their protein targets of PXDZD were extracted from TCMSP, SYMMAP, and HERB databases. The targets related to SCZ were acquired from OMIM and DisGeNET databases. The overlapping targets between composite targets and disease targets were used to construct a protein-protein interaction (PPI) network in the STRING database. The identified targets underwent GO and KEGG enrichment analysis, followed by molecular docking studies of the core target proteins and active compounds.

Result: The screening process yielded 285 PXDZD component targets and 1982 disease targets, ultimately leading to the identification of 120 shared targets. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that PXDZD treatment for SCZ engages a diverse range of biological mechanisms, including inflammatory responses and apoptotic processes, while also modulating various signaling pathways such as the PI3K-Akt, mitogen-activated protein kinase (MAPK), and tumor necrosis factor (TNF) signaling pathways. The molecular docking results revealed a strong affinity of Estrogen Receptor 1 (ER1) toward both β-sitosterol and stigmasterol, while kaempferol, β-sitosterol, and stigmasterol demonstrated significant binding potential against TNF-α.

Conclusion: Pingxin Dingzhi Decoction can play a role in treating SCZ through its multi-component, multi-target, and multi-pathway approach.

Keywords: Molecular docking,; Pingxin Dingzhi Decoction,; network pharmacology,; schizophrenia.

Grants and funding

The authors declare that this study received no financial support.