7,8-dihydroxyflavone attenuates NIH IIIA subtype chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) via...

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) represents a prevalent urological disorder characterized by an unfavorable prognosis. Accumulating evidence indicates that suppression of excessive reactive oxygen species (ROS) generation significantly ameliorates its inflammatory manifestations. 7,8-dihydroxyflavone (7,8-DHF), a specific TrkB receptor agonist, which could subsequently trigger downstream signaling pathways such as AKT, demonstrates antioxidant and anti-inflammatory properties across diverse pathological conditions. Nevertheless, its potential therapeutic efficacy against CP/CPPS remains undefined. The aim of this study is to investigate the effects of 7,8-DHF on CP/CPPS and elucidate the underlying mechanisms involved, thereby providing fundamental experimental data for the clinical research of pharmacological interventions for CP/CPPS.

CP/CPPS rat model was established via intraprostatic injection of complete Freund's adjuvant (CFA). Utilizing this experimental prostatitis model, we evaluated the effects of 7,8-DHF on prostate index, mechanical hyperalgesia, prostate histopathology, oxidative stress markers, pro-inflammatory cytokine expression, and immune cell infiltration. Molecular analyses further assessed TrkB/AKT/SIRT3 signaling pathways in RWPE-1 cells. We have cultivated human prostate epithelial cells RWPE-1. In vitro cell models were constructed through lipopolysaccharide (LPS) induction. The effects of 7,8-DHF on LPS-induced cellular damage and inflammatory responses were validated through Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA) assays.

At the animal level, 7,8-DHF administration concurrently suppressed CFA-induced elevations in prostate index, mechanical hyperalgesia, inflammatory cell infiltration, and pro-inflammatory cytokine levels, while significantly ameliorating histological damage. At the cellular level, 7,8-DHF attenuates LPS-induced cellular damage and inflammatory responses through mechanisms involving the activation of TrkB/AKT/SIRT3 signaling, augmented antioxidant enzyme activity, mitigated ROS overproduction and pro-inflammatory mediator expression, thus disrupting the "oxidative stress-inflammation" vicious cycle.

This study identifies 7,8-DHF as a novel therapeutic agent for CP/CPPS, and the potential role of the TrkB/AKT/SIRT3 pathway in the improvement of CP/CPPS by 7,8-DHF, thereby establishing a foundational basis for future CP/CPPS therapeutics.