Artesunate ameliorates DSS-induced ulcerative colitis by protecting intestinal barrier and inhibiting inflammatory response

• Published in: Inflammation Vol. 43; no. 2; pp. 765 - 776
• Main Authors: Yin, ShaoJie, Yang, HaiFeng, Tao, Ya, Wei, SiMin, Li, LiuHui, Liu, MingJiang, Li, JinGui
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2020; Springer Nature B.V
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Apoptosis; Artesunate; Artesunate - pharmacology; Artesunate - therapeutic use; BAX protein; Bcl-2 protein; Biomedical and Life Sciences; Biomedicine; Body weight; Body weight loss; Caspase-3; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - metabolism; Colon; Dextran; Dextran sulfate; Dextran Sulfate - toxicity; Epithelial cells; Female; Goblet cells; IL-1β; Immunofluorescence; Immunology; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Inflammatory bowel disease; Inflammatory bowel diseases; Interleukin 10; Interleukin 6; Internal Medicine; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestine; Mice; Mice, Inbred ICR; Mucosa; NF-κB protein; Original Article; Pathology; Pharmacology/Toxicology; Phosphorylation; Rheumatology; Scanning electron microscopy; Tumor necrosis factor-α; Ulcerative colitis; ulcerative colitis; artesunate; intestinal barrier; inflammation
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-019-01164-1

There are very few reports on the protective effect of artesunate (ARS) in ulcerative colitis (UC). This study focused on the efficacy of ARS on intestinal barrier, inflammatory response, and potential mechanism in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. The results suggested that ARS treatment markedly alleviated DSS-induced clinical symptoms by relieving body weight loss, the disease activity index (DAI) score, and preventing colonic shortening. HE staining and scanning electron microscope analysis revealed that ARS treatment significantly protected the integrity of intestinal barrier through alleviating DSS-induced erosion of surface epithelial cells, reduction of goblet cells, and destruction of the crypt accompanied with inflammatory cells infiltration. Immunofluorescence histochemical staining and western blot assay confirmed that ARS notably inhibited the loss of Muc2 and claudin-1 in mucosal layer with a relative higher level of Bcl-2/Bax ratio and, moreover, inhibited cleaved-caspase-3 expression in colon tissue. In addition, this study reconfirmed the anti-inflammatory function of ARS evidenced by remarkably suppressing the phosphorylation of nuclear factor-κBα (IκBα) and NF-κB p65 and the expression of IL-1β, IL-6, and TNF-α while enhancing IL-10 expression. Taken together, these data highlight that ARS has the protective effect on UC through maintaining the expression of intestinal mucosal barrier-related proteins, suppressing the apoptosis and inflammatory response. This study may facilitate to understand the action mechanism of ARS against UC.