Lacidipine inhibits NF-κB and Notch pathways and mitigates DSS-induced colitis

Abstract Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon, with its global incidence on the rise, yet effective treatments remain limited. Through screening using an NF-kB promoter dual fluorescence reporter system, we identified the anti-hypertension drug lacidipine as capable of effectively inhibiting p65 and IκBα phosphorylation. In a murine model of dextran sulfate sodium (DSS)-induced colitis, lacidipine demonstrated the ability to mitigate colon lesions and reduce inflammation markers. Target analysis revealed a notable enrichment of the Notch signal. Furthermore, lacidipine treatment inhibited both NF-kB and Notch activation in the colon stimulated by DSS. In summary, our study highlights lacidipine's potential in alleviating UC, presenting it as a promising candidate drug for UC treatment.