Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota.

Abstract

Ulcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.

• Authors: Jiaqi Wu, Yuzheng Wu, Yue Chen, Mengyang Liu, Haiyang Yu, Yi Zhang, Tao Wang
• Journal: Planta medica (Planta Med) Vol. 88 Issue 7 Pg. 559-569 (Jun 2022) ISSN: 1439-0221 [Electronic] Germany
• PMID: 34098585 (Publication Type: Journal Article)
• Copyright: Thieme. All rights reserved.

Chemical References

• Xanthenes
• desmethylbellidifolin
• Dextran Sulfate

Topics

• Animals
• Colitis (chemically induced, drug therapy)
• Colitis, Ulcerative (chemically induced, drug therapy, pathology)
• Colon
• Dextran Sulfate
• Disease Models, Animal
• Gastrointestinal Microbiome
• Humans
• Inflammation (pathology)
• Mice
• Mice, Inbred C57BL
• Xanthenes