[Mechanistic study on improvement of chronic prostatitis by Baojing Tablets via STAT3/HIF-1α/glycolysis axis]

This study investigated the therapeutic mechanism of Baojing Tablets(BJT) in the treatment of chronic prostatitis through the signal transducer and activator of transcription 3(STAT3)/hypoxia-inducible factor 1α(HIF-1α)/glycolysis axis. A rat model of experimental autoimmune prostatitis was established to evaluate the efficacy of Baojing Tablets. Male Wistar rats were randomly divided into six groups(7 per group): control group, model group, low-, medium-, and high-dose Baojing Tablets groups(197.2, 591.5, 1 774.4 mg·kg~(-1), respectively), and a positive control group(Pusitai, 34.2 mg·kg~(-1)). After model induction, all treatments were administered continuously for four weeks. Hematoxylin and eosin(HE) staining was used to observe inflammatory infiltration and glandular damage in the prostate. Serum levels of interleukin-8(IL-8), interleukin-1β(IL-1β), and immunoglobulin G(IgG) were measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of phosphorylated STAT3(p-STAT3), HIF-1α, multiple inositol polyphosphate phosphatase 1(MINPP1), and hexokinase(HK) in prostate tissues were detected by Western blot and immunohistochemistry. Untargeted metabolomics was employed to screen differential metabolites and analyze relevant metabolic pathways, thereby investigating the potential mechanism of Baojing Tablets in treating chronic prostatitis. HE staining results revealed that Baojing Tablets significantly ameliorated pathological damage to the prostate. ELISA results demonstrated that Baojing Tablets reduced serum levels of IL-8, IL-1β, and IgG. Western blot and immunohistochemistry analyses revealed that Baojing Tablets downregulated the expression levels of p-STAT3, HK, and HIF-1α in prostate tissues, while upregulating MINPP1 expression. Metabolomics results suggested that Baojing Tablets may exert its therapeutic effect by modulating 96 differential metabolites and participating in metabolic pathways such as glycolysis and arachidonic acid metabolism. In conclusion, Baojing Tablets may alleviate inflammation and inhibit the progression of chronic prostatitis by targeting STAT3 and suppressing the HIF-1 signaling pathway, thereby modulating glycolytic metabolism.