Baicalein ameliorates TNBS-induced colitis by suppressing TLR4/MyD88 signaling cascade and NLRP3 inflammasome activation in mice

doi:10.1038/s41598-017-12562-6

	Baicalein ameliorates TNBS-induced colitis by suppressing TLR4/MyD88 signaling cascade and NLRP3 inflammasome activation in mice
	Luo, Xiaoping 2; Yu, Zhilun 2; Deng, Chao 2; Zhang, Jingjing 2; Ren, Gaiyan 2; Sun, Aning 2; Mani, Sridhar 1; Wang, Zhengtao 2; Dou, Wei 2
刊名	Scientific reports
	2017-11-27
卷号	7 期号:1 页码:16374
ISSN号	2045-2322
DOI	10.1038/s41598-017-12562-6
文献子类	Article
英文摘要	Baicalein (5,6,7-trihydroxyflavone), a predominant bioactive component isolated from the root of Scutellaria baicalensis Georgi, has established potent anti-inflammatory activity via multi-targeted mechanisms. However, little is known about the effect of baicalein on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, which shares pathology related to human Crohn's disease (CD). The present study demonstrated that baicalein alleviated the severity of TNBS-induced colitis in mice by decreasing the activity of myeloperoxidase (MPO) and the expression of pro-inflammatory mediators. The decline in the activation of nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) correlated with a decrease in the expression of mucosal toll-like receptor 4 (TLR4) and its adaptor myeloid differentiation factor 88 (MyD88). In vitro, baicalein down-regulated the TLR4/MyD88 signaling cascades (NF-κB and MAPKs) in lipopolysaccharide (LPS)-stimulated macrophages. At the upstream level, baicalein bound to the hydrophobic region of the myeloid differentiation protein-2 (MD-2) pocket and inhibited the formation of the LPS-induced MD-2/TLR4 complex. Furthermore, baicalein reduced NOD-like receptor 3 (NLRP3) inflammasome activation and downstream interleukin-1β expression in a dose-dependent manner. Our study provided evidence for the first time that baicalein attenuated TNBS-induced colitis, at least in part, via inhibition of TLR4/MyD88 signaling cascade as well as inactivation of NLRP3 inflammasome.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266405]
专题	中国科学院上海药物研究所
通讯作者	Wang, Zhengtao; Dou, Wei
作者单位	1.Departments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, New York, 10461, USA 2.Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China;
推荐引用方式 GB/T 7714	Luo, Xiaoping,Yu, Zhilun,Deng, Chao,et al. Baicalein ameliorates TNBS-induced colitis by suppressing TLR4/MyD88 signaling cascade and NLRP3 inflammasome activation in mice[J]. Scientific reports,2017,7(1):16374.
APA	Luo, Xiaoping.,Yu, Zhilun.,Deng, Chao.,Zhang, Jingjing.,Ren, Gaiyan.,...&Dou, Wei.(2017).Baicalein ameliorates TNBS-induced colitis by suppressing TLR4/MyD88 signaling cascade and NLRP3 inflammasome activation in mice.Scientific reports,7(1),16374.
MLA	Luo, Xiaoping,et al."Baicalein ameliorates TNBS-induced colitis by suppressing TLR4/MyD88 signaling cascade and NLRP3 inflammasome activation in mice".Scientific reports 7.1(2017):16374.