The protective role of nicardipine in dextran sulfate sodium-induced colitis in mice: Modulating inflammation and apoptosis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with persistent inflammation, oxidative stress, and epithelial apoptosis. Nicardipine, a dihydropyridine calcium channel blocker, exhibits anti-inflammatory and anti-apoptotic properties, but its therapeutic potential in UC remains unclear. This study evaluated the effects of nicardipine on dextran sulfate sodium (DSS)-induced colitis in mice, focusing on inflammatory, oxidative, and apoptotic pathways. Fifty BALB/c mice were assigned to five groups (n = 10): control, DSS, nicardipine 12 mg/kg, nicardipine 24 mg/kg, and 5-aminosalicylate (ASA) 75 mg/kg. Treatments were administered for 3 days before and 10 days during DSS exposure. Disease severity was assessed by body weight, disease activity index (DAI), and colon length. Colonic mRNA levels of Nlrp3, TNF-α, IL-17, and TNFSF10 were quantified by RT-PCR; protein expression of caspase-3, caspase-8, BAX, and BCL-2 was analyzed by Western blot. Serum malondialdehyde (MDA), myeloperoxidase (MPO), glutathione peroxidase-1 (GPX-1), occludin, and prostaglandin E₂ (PGE-2) were measured by ELISA. Histological scoring assessed epithelial integrity and inflammation. Nicardipine dose-dependently reduced DSS-induced weight loss, DAI, and colon shortening. Both doses significantly downregulated Nlrp3, TNF-α, IL-17, and TNFSF10 (p < 0.05), decreased caspase-3 and BAX, and increased BCL-2. Nicardipine restored GPX-1, lowered MDA and MPO, preserved occludin, and reduced PGE-2. Histology confirmed reduced mucosal injury and preserved epithelial architecture. Nicardipine attenuates DSS-induced colitis by suppressing pro-inflammatory cytokines, reducing oxidative stress, and inhibiting apoptosis, supporting its potential as a therapeutic candidate for UC. Further studies are warranted to clarify its molecular mechanisms and clinical relevance.