Saikosaponin D alleviates chronic prostatitis/chronic pelvic pain syndrome by regulating the NF-κB pathway via lncRNA5682.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological disorder characterised by persistent pelvic pain and chronic inflammation that can trigger depressive symptoms and significantly negatively affect patients' health and quality of life. Current clinical treatment outcomes are unsatisfactory. Saikosaponin D is a triterpenoid saponin that is primarily isolated from the roots of Bupleurum chinense and related Bupleurum species. Bupleurum is a traditional medicinal plant genus that is extensively utilised in East Asian ethnomedicine. SSD has been reported to possess anti-inflammatory, immunomodulatory, and antifibrotic properties. However, its therapeutic potential in CP/CPPS remains unclear. AIM OF THE STUDY: This study was designed to assess the therapeutic effect of saikosaponin D in an experimental autoimmune prostatitis (EAP) mouse model and to investigate its underlying mechanisms. MATERIALS AND METHODS: Male C57BL/6 mice were immunised with rat prostate extract emulsified in complete Freund's adjuvant to induce EAP and subsequently treated with high-dose and low-dose SSD. The pelvic pain thresholds were assessed by von Frey filaments, depressive-like behaviours by forced swim tests, and histopathological alterations by haematoxylin-eosin staining. Multiomics analyses, including RNA sequencing, RT‒qPCR, Western blotting, ELISA, immunofluorescence, and flow cytometry, were employed to profile transcriptomic changes, cytokine levels, and immune cell phenotypes. RESULTS: SSD treatment significantly increased pain thresholds, alleviated depressive-like behaviour, and reduced prostatic inflammation and tissue damage. Transcriptomic analysis revealed that NF-κB signalling is a major pathway regulated by SSD. Mechanistically, SSD suppressed aberrantly upregulated lncRNA5682 expression, thereby inhibiting NF-κB activation, reducing the number of proinflammatory monocytes/macrophages, and promoting M2 macrophage polarisation. CONCLUSION: SSD has potent anti-inflammatory, analgesic, and immunomodulatory effects on CP/CPPS through inhibition of the lncRNA5682/NF-κB axis, highlighting its potential as a promising therapeutic agent for chronic prostatitis.