Curculigoside mitigates dextran sulfate sodium‑induced colitis by activation of KEAP1‑NRF2 interaction to inhibit oxidative damage and autophagy of intestinal epithelium barrier.

Curculigoside (CUR), a primary active ingredient of , serves an important role in the intervention of numerous diseases, including ulcerative colitis, rheumatoid arthritis, myocardial ischemia, etc. However its specific mechanisms of therapy have not been fully elucidated. The aim of the present study was to elucidate the mechanisms underlying the anti‑oxidative stress and anti‑ulcerative colitis (UC) effects of CUR. Mouse model of dextran sulfate sodium (DSS)‑induced colitis, along with Caco2 and mouse intestine organoid models were used. The effect of CUR on mitigating the symptoms of chronic colitis was investigated. Through ELISA experiments, it was observed that CUR alleviated the inflammation status in mice with chronic colitis. This was evidenced by the downregulation of inflammatory cytokines such as TNF‑α and IL‑6 and ‑1β and decreased neutrophil infiltration along with downregulated myeloperoxidase activity. CUR helped in maintaining the barrier functions of intestinal epithelium. TNF‑α stimulation of organoids and H2O2 stimulation of Caco2 cells demonstrated the capabilities of CUR to rescue cells from oxidative stress. There was activation of Nrf2 both and , accompanied by enhanced autophagy. Mechanistic studies of cells and Nrf2 knockout mice demonstrated that Nrf2 served a pivotal role in inhibition of UC by curculigoside via interaction with Kelch‑like ECH‑associated protein 1 (Keap1). and experiments confirmed that CUR activated Nrf2 via Keap1/Nrf2 interaction, resulting in decreased oxidative stress and promoted autophagy. These findings demonstrated that CUR could effectively mitigate colitis and may have clinical application in UC therapy.