摘要
OBJECTIVE: To elucidate the protective effect of Qingdai (indigo Naturalis, QD) on ulcerative colitis (UC) by means of in silico and in vivo approaches.METHODS: A systems pharmacology analysis was per-formed to predict the active components of QD whereas the putative biological targets of QD against UC were obtained through target fishing, network cons-truction and enrichment analyses. Meanwhile, we examined the ameliorative effect of QD in a mouse model of dextran sulfate sodium (DSS)-induced colitis. During the 10-day experiment, the control and diseased mice were given with oral gavages of QD (1.3 g raw herbs middot kg-1middot d-1) or 5-aminosalicylic acid (5-ASA, 100 mgmiddotkg-1middotd-1) every day. The underlying pharma-cological mechanisms of QD in UC were determined using polymerase chain reaction tests, histological staining, enzyme-linked immunoassays, and Western blotting analysis. RESULTS: Searching from various network pharmacology databases, 29 compounds were identified in QD. According to the screening criteria suggested by TCMSP (i.e. OB >_ 30% and DL >_ 0.18), nine of them were considered the active ingredients that contribute to the ameliorative effects of QD on different mouse models of colitis. Most importantly, the protective effect of QD on DSS-induced colitis was significantly associated with modulations of the expression levels of glycogen synthase kinase 3-beta (Gsk3-beta) and forkhead box p3 (Foxp3), which are widely considered as important regulators of excessive inflammatory responses.CONCLUSIONS: The results of this study provide solid scientific evidence for the use of QD or its core active components in the clinical management of UC.
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单位1; 广州中医药大学