Exploring the Molecular Mechanisms of Xuefu Zhuyu Pills in Treating Antipsychotic-Induced Hyperprolactinemia: An Integrated Approach Based on Plasma Component Analysis, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations.

INTRODUCTION Antipsychotic-induced hyperprolactinemia (HPRL) is a prevalent and troubling side effect that impairs treatment adherence. Xuefu Zhuyu Pills (XFZY), a traditional Chinese medicine formula, have shown efficacy in clinical practice; however, their active components and mechanisms of action remain unknown.

Methods

We identified the components of XFZY in human plasma by UPLC-Q-TOF-MS/MS and performed network pharmacology analysis to screen key targets and core active components through topological analysis. Intersecting targets were subjected to GO and KEGG enrichment analyses on Metascape, followed by molecular docking and molecular dynamics simulations to assess binding stability between core active components and key targets.

Results

A total of 67 absorbed components were found in human plasma. Based on the network pharmacology results, we identified seven core targets (AKT1, ESR1, IL6, TNF, ERBB2, CTNNB1, and MAOA) and three potential active ingredients (Makisterone B, 3-O-beta-Dglucopyranosylplatycodigenin, and 4',5,6,7-Tetramethoxyflavone). GO and KEGG suggested that hormone level regulation, the neuroactive ligand-receptor interaction, the apelin signaling pathway, and the cGMP-PKG signaling pathway may play key roles in treating HPRL caused by antipsychotic drugs.

Discussion

Molecular docking results showed that the core active ingredient binds well with the key targets, and molecular dynamics simulations further verified their stability.

Conclusion

This study preliminarily revealed the components in human plasma of XFZY in HPRL treatment and their potential pharmacological mechanism. These findings provide a scientific basis for clinical studies.