机构：[1]School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China[2]First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China深圳市中医院深圳医学信息中心[3]School of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China[4]Department of Laboratory Medicine, Affiliated Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Oroxindin is a flavonoid isolated from the traditional Chinese medicine Huang-Qin, which has shown various pharmacological activities including anti-inflammatory, antitumor, antioxidant, etc. Thus far, the effect of oroxindin on colonic inflammation and the underlying mechanism remain unknown. In this study, we investigated the tissue distribution of oroxindin and its therapeutic effects on ulcerative colitis (UC) as well as the underlying mechanisms. UC model was established in mice by administrating dextran sulfate sodium (DSS) in drinking water for 7 d. We first showed that oroxindin was largely absorbed by the colon as an active ingredient after normal mice received Huang-Qin-Tang, a traditional Chinese medicine decoction. UC mice were then treated with oroxindin (12.5, 25, 50 mg ·kg-1 ·d-1, i.g.) for 10 d. We found that oroxindin treatment greatly suppressed massive macrophages infiltration and attenuated pathological changes in colonic tissue. Furthermore, oroxindin treatment significantly inhibited the generation of IL-1β and IL-18 in the colon via inhibiting the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome formation and activation. In cultured macrophages, LPS induced NLRP3 inflammasome formation and caspase-1 activation, which were suppressed by oroxindin (12.5-50 μM). In LPS-treated macrophages, oroxindin dose-dependently restored the expression of TXNIP protein, leading to suppressing TXNIP-dependent NF-κB activation. In conclusion, these results demonstrate that oroxindin could be absorbed by the colon and attenuate inflammatory responses via inhibiting NLRP3 inflammasome formation and activation, which is related to the inhibitory effect on TXNIP-dependent NF-κB-signaling pathway. Hence, oroxindin has the potential of becoming an effective drug for treating UC.
基金：
National Natural Science Foundation of China
(81603587, 81603668); the Guangdong Natural Science Funds for Distinguished
Young Scholar (No. 2018B030306027); the Key projects of basic research in
Guangdong Province (No. A1-AFD018191A100); the Science & Technology Award
for Young-aged Talents of China Association of Traditional Chinese Medicine (No.
CACM-2017-QNRC2-C12); the Project of Guangzhou University of Chinese Medicine
(No. A3-040219415009, A1-AFD018191A41); and by the Key Research and Development
Program of Guangdong Province (2018KZDXM023).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|2 区医学
小类|2 区化学综合2 区药学
最新[2025]版：
大类|2 区医学
小类|1 区药学2 区化学：综合
第一作者：
第一作者机构：[1]School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Liu Qi,Zuo Rui,Wang Kai,et al.Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway.[J].Acta Pharmacologica Sinica.2020,41(6):771-781.doi:10.1038/s41401-019-0335-4.
APA：
Liu Qi,Zuo Rui,Wang Kai,Nong Fei-Fei,Fu Ya-Jun...&Chen Yang.(2020).Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway..Acta Pharmacologica Sinica,41,(6)
MLA：
Liu Qi,et al."Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway.".Acta Pharmacologica Sinica 41..6(2020):771-781
