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

Xiaoping Luo, Zhilun Yu, Chao Deng, Jingjing Zhang, Gaiyan Ren, Aning Sun, Sridhar Mani, Zhengtao Wang, Wei Dou

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Abstract

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.

Original languageEnglish (US)
Article number16374
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Myeloid Differentiation Factor 88
Trinitrobenzenes
Inflammasomes
Toll-Like Receptor 4
Sulfonic Acids
Colitis
NF-kappa B
Lipopolysaccharides
Scutellaria baicalensis
NLR Proteins
baicalein
p38 Mitogen-Activated Protein Kinases
Interleukin-1
Crohn Disease
Peroxidase
Proteins
Anti-Inflammatory Agents
Macrophages
Pathology

ASJC Scopus subject areas

  • General

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Baicalein ameliorates TNBS-induced colitis by suppressing TLR4/MyD88 signaling cascade and NLRP3 inflammasome activation in mice. / Luo, Xiaoping; Yu, Zhilun; Deng, Chao; Zhang, Jingjing; Ren, Gaiyan; Sun, Aning; Mani, Sridhar; Wang, Zhengtao; Dou, Wei.

In: Scientific Reports, Vol. 7, No. 1, 16374, 01.12.2017.

Research output: Contribution to journalArticle

Luo, Xiaoping ; Yu, Zhilun ; Deng, Chao ; Zhang, Jingjing ; Ren, Gaiyan ; Sun, Aning ; Mani, Sridhar ; Wang, Zhengtao ; Dou, Wei. / Baicalein ameliorates TNBS-induced colitis by suppressing TLR4/MyD88 signaling cascade and NLRP3 inflammasome activation in mice. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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