Exploring the Active Components of Buqi‐Zhitong‐Decoction and Its Therapeutic Potential for Chronic Fatigue Syndrome Based on LC‐MS/MS and Network Pharmacology

Chronic fatigue syndrome (CFS) is a complex condition that requires effective intervention and treatment. Buqi-Zhitong-Decoction (BQZTD), an empirical formula, has been used clinically to treat CFS and has shown good clinical results. However, the underlying bioactive components and mechanism of action for its treatment of CFS remain unclear. This study is based on the serum pharmacochemistry method, utilizing LC-MS/MS technology for detection and analysis of BQZTD water extracts and their components entering the bloodstream. A total of 98 compounds were preliminarily identified from the BQZTD. Furthermore, 44 ingredients were detected in rat serum, including 19 prototype components and 25 metabolite components. The results of network pharmacology analysis indicated that the BQZTD might improve CFS by regulating immune, inflammatory, neuroendocrine system, and energy metabolism-related pathways. In addition, Prostaglandin-Endoperoxide Synthase 2 (PTGS2) plays a central role in the regulatory network. Molecular docking simulations with six potential active components in serum revealed that all of them exhibit high affinity for PTGS2, with compound Isoformononetin showing the strongest binding affinity. This study represents the first comprehensive identification of the chemical components, targets, and signaling pathways of BQZTD, clarifying its potential mechanism of action in treating CFS. The research findings provide a reference basis for pharmacodynamic studies and quality control.