7,8-Dihydroxyflavone alleviates chronic prostatitis/chronic pelvic pain syndrome via modulation of the TrkB/AKT/ERK/SIRT3 signaling axis.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological condition marked by ongoing oxidative stress and persistent inflammation, which complicates clinical management. This study examined the therapeutic effects and underlying mechanisms of 7,8-Dihydroxyflavone (7,8-DHF) in an experimental autoimmune prostatitis (EAP) mouse model, induced via subcutaneous immunization with prostate antigen in Complete Freund's Adjuvant. Mice were administered daily intraperitoneal injections of 7,8-DHF (5 mg/kg) and subsequently underwent a series of evaluations: prostate index measurement, abdominal tactile allodynia assessment using Von Frey filaments, cystometric analysis for urinary function, histological examinations with HE and Masson staining, quantitative PCR for pro-inflammatory cytokines, biochemical assays for oxidative stress markers (MDA, SOD, CAT, total antioxidant capacity), and Western blot analysis to assess activation of the TrkB/AKT/ERK/SIRT3 signaling pathway. 7,8-DHF treatment significantly decreased the prostate index, alleviated pelvic tactile allodynia, and improved bladder function in EAP mice. Histopathological analysis showed notable reductions in inflammatory cell infiltration and collagen deposition, along with decreased expression of pro-inflammatory cytokines (IL-6, IL-17α, MCP-1, IL-1β). Mechanistically, 7,8-DHF enhanced antioxidant capacity by increasing SOD/CAT activities and decreasing MDA levels, which correlated with TrkB phosphorylation, subsequent AKT/ERK pathway activation, upregulated SIRT3 expression, and MnSOD deacetylation. In vitro experiments with RWPE-1 cells demonstrated that 7,8-DHF mitigates LPS-induced oxidative stress and inflammation through mechanisms dependent on SIRT3. Collectively, these findings elucidated that 7,8-DHF could ameliorate CP/CPPS by activating the TrkB/AKT/ERK/SIRT3 signaling pathway to suppress oxidative stress and inflammatory reactions, highlighting its potential value as a novel therapeutic candidate for the clinical management of CP/CPPS.