机构地区:[1]Department of orthopedics,the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China [2]the First School of Clinical Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510405,China [3]Department of Gastroenterology,the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Zhengzhou 450046,China [4]Basic Medical College,Henan University of Chinese Medicine,Guangzhou 510405,China
出 处:《Journal of Traditional Chinese Medicine》2023年第1期124-133,共10页中医杂志(英文版)
基 金:Supported by Natural Science Foundation of Guangdong Province:Mechanism of Chang-An Decotion in Neuropeptide Spexin related GSK-3βRegulating Intestinal Nerve Immune Network in Ulcerative Colitis(No.2018A030310614);National Natural Science Foundation of China:Mchanism of Chang-An Decotion in Intestinal Mucosal Immunity of Ulcerative Colitis on Exocrine Mediated Rab27(No.81903963);Department of Education of Guangdong Province Project:Mchanism of Chang-An decotion of Ulcerative Colitis on Exocrine Mediated GSK-3βRegulating Th17/Treg in Ulcerative Colitis(No.2017KQNCX045)。
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 performed 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·kg^(-1)·d^(-1))or 5-aminosalicylic acid(5-ASA,100 mg·kg^(-1)·d^(-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-β(Gsk3-β)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.
关 键 词:Qingdai(Indigo Naturalis) colitis ulcerative glycogen synthase kinase 3 beta signaling transduction forkhead transcription factors network pharmacology
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