Baicalin ameliorates interstitial cystitis/bladder pain syndrome by inhibiting the TLR4/NF-κB pathway.

Abstract

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disorder characterized by pelvic pain and urinary symptoms, yet effective therapeutic options remain limited. Baicalin (BA), a bioactive flavonoid derived from Scutellaria baicalensis, exhibits anti-inflammatory and antioxidant properties, though its role in IC/BPS has not been fully elucidated. This study demonstrates that BA significantly ameliorates cyclophosphamide-induced urination frequency and bladder tissue damage and reduces serum levels of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, in a rat model of IC/BPS. Integrated analysis of network pharmacology, metabolomics, molecular docking, and experimental validation elucidated the potential mechanism by which BA treats IC/BPS through regulation of the TLR4/NF-κB signaling pathway.Network pharmacological analysis identified 13 core targets, and both KEGG pathway enrichment and metabolomics results indicated significant enrichment of the NF-κB signaling pathway. Molecular docking confirmed strong binding affinities between BA and TLR4, MYD88, and NF-κB p65, with binding energies below - 7.0 kcal/mol. Western blot analysis further verified that BA treatment downregulated the expression of these key signaling molecules. These results indicate that BA alleviates IC/BPS primarily by suppressing the TLR4/NF-κB pathway, thereby attenuating inflammation and restoring metabolic balance. Our findings provide a mechanistic basis for the application of BA in IC/BPS treatment and support its potential for clinical translation.