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

Abstract

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

Ameliorated Effects of Fucoidan on Dextran Sulfate Sodium-Induced Ulcerative Colitis and Accompanying Anxiety and Depressive Behaviors in Aged C57BL/6 Mice

“…As the physical barrier of the gut, the intestinal barrier is important to protect the organism from external attacks, and gingerenone A attenuates UC via targeting IL-17RA to restore the intestinal barrier function . Moreover, the increased permeability of intestine causes inflammation factors and bacterial toxins enter the bloodstream and indirectly affects the central nervous system. , Meanwhile, the blood-brain barrier protects central neurons and is highly associated with systemic inflammation; thus, alleviated colonic histopathological damage and enhanced intestinal and blood-brain barrier function might also contribute to the amelioration of UC and UC associated anxiety- and depression-like behaviors.…”

Structural analysis and blood-enriching effects comparison based on biological potency of Angelica sinensis polysaccharides

“…There is a strong link between inflammation and BDS. Inflammation affects blood circulation by interfering with the immune system and gut barrier function, and controlling inflammation is important in the prevention and treatment of BDS ( Liang et al, 2024 ). Bioefficacy can better reflect the overall activity and clinical efficacy of TCMs, and a high level of efficacy can be directly quantified using the bioefficacy assay of TCMs.…”