Gingerenone A Attenuates Ulcerative Colitis via Targeting IL‐17RA to Inhibit Inflammation and Restore Intestinal Barrier Function

• DOI: 10.1002/advs.202400206
• Publication Date: 2024-04-19T11:43:29Z
• Authors: Jian Liang; Weigang Dai; Chuanghui Liu; Yifan Wen; Chen Chen; Yifei Xu; Song Huang; Shaozhen Hou; Chun Li; Yongming Chen; Wei Wang; Hailin Tang
• Keywords: Barrier function

Abstract Ulcerative colitis (UC) is a complicated and recurrent intestinal disease. Currently available drugs for UC treatment are scarce, therefore, novel therapeutic the urgently to be developed. Gingerenone A (GA) phenolic compound known its anti‐inflammatory effect, but effect on remains unknown. Here, it shown that GA protects mice against UC, which closely associated with inhibiting mucosal inflammation enhancing barrier integrity in vivo vitro. Of note, RNA sequencing analysis demonstrates an evident correlation IL‐17 signaling pathway after treatment, this further corroborated by Western blot. Mechanistically, directly interacts IL‐17RA protein through pull‐down, surface plasmon resonance molecular dynamics simulation. Importantly, lentivirus‐mediated IL‐17RA/Act1 knock‐down or co‐treatment brodalumab/ixekizumab significantly impairs protective effects of DSS‐induced dysfunction, suggesting critical role GA‐mediated protection UC. Overall, these results indicate effective agent mainly direct binding inhibit inflammatory activation.