Mechanism of Qianlie Zhitong Formula Against Chronic Prostatitis Based on Proteomics and Metabolomics

ABSTRACT

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent pelvic pain disorder in men, yet effective pharmacotherapies remain limited. Emerging evidence suggests that oxidative stress and dysregulated iron metabolism contribute to the pathogenesis of CP/CPPS, with ferroptosis increasingly implicated in CP/CPPS‐related pathology. Qianlie Zhitong Formula (QLZTF) has shown therapeutic potential in treating CP/CPPS; however, its underlying mechanisms remain incompletely understood. This study integrated proteomics, metabolomics, and in vivo experiments to investigate the therapeutic mechanisms of QLZTF. A carrageenan‐induced rat model was established, and rats were randomly assigned to five groups: control, model, Qianliekang, low‐dose QLZTF, and high‐dose QLZTF. QLZTF significantly reduced inflammatory cytokines (TNF‐α, IL‐6, and IL‐1β), alleviated pain responses, and ameliorated prostate tissue injury. Proteomic analysis identified BCAT2, ALDH1B1, and ALDH2 as significantly upregulated proteins closely associated with ferroptosis. KEGG enrichment analysis of both proteomic and metabolomic data revealed that pantothenate and CoA biosynthesis and branched‐chain amino acid (BCAA) degradation pathways were significantly enriched. Integrated analysis indicated that QLZTF synergistically regulates these pathways, activates the BCAT2/ALDH axis, and inhibits ferroptosis, thereby alleviating inflammation, pain, and fibrosis in CP/CPPS. This study provides the first multiomics evidence for the anti‐ferroptotic mechanism of QLZTF.