Natural Dietary Flavonoid Apigenin Mitigates Ulcerative Colitis via Modulating the AMPK/NF-κB/NLRP3 Signaling Axis

Ulcerative colitis (UC) is a challenging inflammatory disease with higher relapse and lower remission rates, urgently requiring effective and safe complementary treatment options. Apigenin (Api), a natural flavonoid from parsley and celery, exhibits potent antioxidant and anti-inflammatory activities. In mice with 2.5% DSS-induced acute colitis, Api markedly alleviated weight loss, colon shortening, and elevated DAI scores, while restoring mucosal integrity and reducing oxidative stress and inflammation. Mechanistically, Api can directly bind to AMPK to activate it, thereby alleviating oxidative stress and suppressing the NF-κB pathway, which in turn inhibits NLRP3 inflammasome activation. Moreover, Api directly binds to NLRP3, thereby inhibiting inflammasome activation. Through dual targeting of AMPK and NLRP3, Api cooperatively suppresses oxidative stress and inflammation in UC mice. Collectively, these findings demonstrate that Api protects against colitis via modulation of the AMPK/NF-κB/NLRP3 axis, highlighting its potential as a natural anti-inflammatory agent for intestinal health.