Abstract
In this study, we investigated the therapeutic effects and mechanism of atractylodin (ATL) on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. We found that atractylodin could significantly reverse the effects of DSS-induced ulcerative colitis, such as weight loss, disease activity index score; shorten the colon length, and reverse the pathological changes in the colon of mice. Atractylodin could inhibit the activation of colonic macrophages by inhibiting the MAPK pathway and alleviate intestinal inflammation in the mouse model of ulcerative colitis. Moreover, it could protect the intestinal barrier by inhibiting the decrease of the tight junction proteins, ZO-1, occludin, and MUC2. Additionally, atractylodin could decrease the abundance of harmful bacteria and increase that of beneficial bacteria in the intestinal tract of mice, effectively improving the intestinal microecology. In an LPS-induced macrophage model, atractylodin could inhibit the MAPK pathway and expression of the inflammatory factors of macrophages. Atractylodin could also inhibit the production of lactate, which is the end product of glycolysis; inhibit the activity of GAPDH, which is an important rate-limiting enzyme in glycolysis; inhibit the malonylation of GAPDH, and, thus, inhibit the translation of TNF-α. Therefore, ours is the first study to highlight the potential of atractylodin in the treatment of ulcerative colitis and reveal its possible mechanism.
Highlights
Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that affects the colon and rectum
Ulcerative colitis is a debilitating inflammatory disease of the intestine, which may increase the incidence of colon cancer, eventually leading to disturbances in the physical and mental health of individuals (Pandurangan and Esa, 2014)
Our results indicated that atractylodin could reduce the weight loss of mice with UC, control diarrhea and hematochezia, alleviate trauma to the colon, reduce the loss of colonic goblet cells, and increase the expression of MUC2, ZO-1, and occludin
Summary
Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that affects the colon and rectum. It is one of the two forms of inflammatory bowel disease (IBD). The global incidence of UC is steadily increasing. Local mesalazine continues to be Atractylodin Attenuates DSS-Induced Colitis the first-line treatment for patients with mild or moderate active UC limited to the rectum, whereas oral and local 5-ASA are the main treatment approaches for patients with left or extensive colitis (Cohen and Dalal, 2015). There is an urgent need for the effective management of ulcerative colitis; an increasing number of studies aimed at discovering novel and effective natural products are being conducted
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