Mechanistic insights into nicardipine's anti-colitic action: inhibition of pro-inflammatory cytokines, attenuation of oxidative stress, and protection of the mucosal barrier.

Abstract

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by excessive immune activation and oxidative stress. UC is characterized by elevated inflammatory cytokine levels. Nicardipine is primarily used for the management of hypertension and angina. Beyond its cardiovascular applications, nicardipine has demonstrated anti-inflammatory properties in various experimental disease models. This study investigates the therapeutic role of nicardipine in a murine model of dextran sulfate sodium (DSS)-induced colitis. METHOD: Fifty mice were divided into control, DSS-induced, and two treatment groups (12 and 24 mg/kg nicardipine). Quantitative real-time PCR (RT-PCR) was performed to assess the mRNA expression levels of NF-κB, IL-6, and IL-1β in colon tissues. Protein expression levels of TNF-α, COX-2, and MPO were evaluated using western blot analysis. ELISA was utilized to examine serum levels of Claudin-1, 8-OHdG, and superoxide dismutase. Additionally, histological examination of colon tissues was conducted to assess morphological changes and inflammation. RESULTS: Nicardipine treatment (12 and 24 mg/kg; the higher dose was more effective) ameliorated DSS-induced colitis in mice by reducing weight loss, DAI scores, and histological damage. It suppressed NF-κB mRNA expression and reduced the expression of IL-6, IL-1β, TNF-α, and COX-2. Moreover, nicardipine decreased MPO and 8-OHdG levels, restored claudin-1 expression, and enhanced SOD activity. CONCLUSION: Nicardipine plays a protective role in DSS-induced colitis. This effect appears to be achieved by regulating mechanisms involved in inflammation and oxidative stress.