Acacetin Alleviates DSS-Induced Ulcerative Colitis by Targeting Keap1/Nrf2 Pathway to Inhibit Endoplasmic Reticulum Stress-Mediated Apoptosis

Ulcerative colitis (UC) is a chronic bowel disease with an increasingly high incidence rate, and current therapeutic drugs carry severe side effects. Acacetin is a natural flavonoid compound obtainable from acacia honey, exhibiting broad-spectrum antioxidant activity. However, the role of acacetin on oxidative stress in UC mice and the specific regulatory mechanisms have not been elucidated. Our results indicated acacetin alleviated dextran sulfate sodium salt (DSS)-induced weight loss, decreased the disease activity index (DAI), shortened colon length. Furthermore, acacetin also inhibited inflammatory response, oxidative stress and endoplasmic reticulum stress (ERS)-mediated Apoptosis, which may be mediated by acacetin targeting the Keap1 protein. Subsequently, Nrf2 knockout suppressed the therapeutic effect of acacetin on UC. This study demonstrates that acacetin alleviates UC by inhibiting oxidative stress and ERS-mediated Apoptosis through targeting the Keap1 protein. Our study provides a solid theoretical support for using acacetin as medicinal foods in the prevention of colitis.

Keap1/Nrf2 signaling pathway; acacetin; apoptosis; endoplasmic reticulum stress; ulcerative colitis.