Ulcerative colitis is a common inflammatory bowel disease, and the activation of thePI3K/AKT and NF-κB signaling pathways plays a pivotal role in its pathogenesis. Dihydroartemisinin (DHA) is a widely used antimalarial drug and has shown anticancer effect partially through inhibiting the activation of PI3K/AKT and NF-κB. This study aimed to investigate the effect of dihydroartemisinin on ulcerative colitis and its mechanism. Adult male C57 mice were subjected to 3.0% dextran sulfate sodium (DSS) for seven days; simultaneously, dihydroartemisinin or control saline was administered by oral gavage once a day. In vitro, the intestinal epithelial cell-6 was treated with LPS for 24 hours with or without dihydroartemisinin combined with PI3K/Akt activator 740 Y-P or NF-κB activator phorbol myristate acetate. Western blotting was used to test the activation of PI3K/AKT and NF-κB. Dihydroartemisinin significantly ameliorated body weight loss, shortened colon length, and increased DAI in DSS-induced colitis. Meanwhile, histological damage was improved and was accompanied by decreased expression and secretion of proinflammatory cytokines. Moreover, DSS-induced elevation of phosphorylation of PI3K, AKT, IKKα, IκBα, and NF-κB (p65) was remarkably blunted by dihydroartemisinin both in vivo and in vitro, indicating an inhibitive property on the PI3K/AKT and NF-κB signaling pathways. Furthermore, administration of 740 Y-P or PMA significantly blocked protective activity of dihydroartemisinin against colitis in vitro. In conclusion, dihydroartemisinin can attenuate DSS-induced colitis, and its anticolitis effect might be mediated via the PI3K/AKT and NF-κB signaling pathways. DHA might serve as a promising drug for patients with ulcerative colitis.
Calcium/Ask1/MKK7/JNK2/c-Src signalling cascade mediates disruption of intestinal epithelial tight junctions by dextran sulfate sodium
