Unlocking betaine's potential: A novel therapeutic avenue for diabetes-induced erectile dysfunction

This study investigated betaine's therapeutic potential for diabetic erectile dysfunction (DMED). DMED rats were divided into DMED, DMED+Betaine (Bet, 400 mg/kg), and control groups. After 8 weeks, erectile function was assessed via cavernous nerve stimulation. Post-assessment, penile tissue was processed: excess fibrous tissue was removed, and corpus cavernosum (CC) was dissected into sections for future analysis. Corpus cavernosum smooth muscle cells (CCSMCs) were isolated, treated with high glucose (HG, 30 mM) ± betaine (1 mM) for one week, then analyzed. DMED rats exhibited impaired erectile function, elevated fibrosis, inflammation, apoptosis, and activation of IKK-α/NF-κB and HDAC3/NF-κB pathways. Betaine administration restored erectile response, improved histology, and suppressed these pathways, reducing inflammatory, fibrotic, and apoptotic markers in DMED rats and HG-treated CCSMCs. Results suggest betaine alleviates DMED by inhibiting IKK-α/NF-κB and HDAC3/NF-κB signaling, highlighting its potential as a novel DMED therapy. • Betaine blocks IKK-α/HDAC3/NF-κB & NLRP3 inflammasome, reducing diabetic cytokines. • Betaine reduces fibrosis and inhibits apoptosis in diabetic models. • Betaine lifts glucose-induced proliferation suppression and apoptosis in CCSMCs. • Betaine downregulates NLRP3, IL-1β, IL-18 under high glucose conditions.