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Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway
Gao, Hongwei1; Liu, Xin1; Sun, Wen1; Kang, Naixin2; Liu, Yanli2; Yang, Shilin2; Xu, Qiong-ming2; Wang, Chunming1; Chen, Xiuping1
2017-08
Source PublicationCELL DEATH & DISEASE
ISSN2041-4889
Volume8
Abstract

Tanshinones belong to a group of lipophilic constituents of Salvia miltiorrhiza Bunge (Danshen), which is widely used in traditional Chinese medicine. A deluge of studies demonstrated that tanshinones exert anti-inflammatory effects, but the underlying mechanisms remain unclear to date. This study investigated the anti-inflammatory effects and mechanisms of total tanshinones (TTN). TTN suppressed the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the secretion of TNF-alpha, IL-6, and IL-1 beta in RAW264.7 cells, bone marrow-derived macrophages, and THP-1 cells. TTN attenuated the LPS-induced transcriptional activity of NF-kappa B and decreased I kappa B-alpha and IKK phosphorylation and NF-kappa B/p65 nuclear translocation. Furthermore, TTN inhibited the LPS-induced transcriptional activity of AP-1, which was induced by the reduction of JNK1/2, ERK1/2, and p38MAPK phosphorylation. TTN blocked LPS-induced Toll-like receptor 4 (TLR4) dimerization, which consequently decreased MyD88 recruitment and TAK1 phosphorylation. In addition, TTN pretreatment effectively inhibited xylene-induced ear edema and LPS-induced septic death and improved LPS-induced acute kidney injury in mice. TTN exerts anti-inflammatory effects in vitro and in vivo by blocking TLR4 dimerization to activate MyD88-TAK1-NF-kappa B/MAPK signaling cascades, which provide the molecular basis of the anti-inflammatory effect of Danshen and suggest that TTN is a potential agent for the treatment of inflammatory diseases.

DOI10.1038/cddis.2017.389
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000409550500041
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:21   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorXu, Qiong-ming; Chen, Xiuping
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
2.Department of Pharmacognosy, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Gao, Hongwei,Liu, Xin,Sun, Wen,et al. Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway[J]. CELL DEATH & DISEASE,2017,8.
APA Gao, Hongwei.,Liu, Xin.,Sun, Wen.,Kang, Naixin.,Liu, Yanli.,...&Chen, Xiuping.(2017).Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway.CELL DEATH & DISEASE,8.
MLA Gao, Hongwei,et al."Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway".CELL DEATH & DISEASE 8(2017).
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