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Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits anti-inflammatory effects through blocking toll-like receptor 4 dimerization
Gao, Hongwei1,2; Cui, Yankun3; Kang, Naixin2; Liu, Xin1; Liu, Yanli2; Zou, Yue2; Zhang, Ziyu2; Li, Xiaoran2; Yang, Shilin2; Li, Ji3; Wang, Chunming1; Xu, Qiong-ming2; Chen, Xiuping1
2017-09
Source PublicationBRITISH JOURNAL OF PHARMACOLOGY
ISSN0007-1188
Volume174Issue:17Pages:2880-2896
Abstract

Background and Purpose

Isoacteoside (is a phenylethanoid isolated from Monochasma savatieri Franch. ex Maxim., which is an anti‐inflammatory herb widely used in traditional Chinese medicine. However, the exact mechanism of the anti‐inflammatory activity of isoacteoside is not completely understood. In this study, its anti‐inflammatory mechanism was elucidated in mouse macrophages.

Experimental Approach

The expression of the NF‐κB pathway, MAPK pathway, iNOS, TNF‐α, IL‐6 and IL‐1β was evaluated using Western blotting, quantitative real‐time PCR or ELISA. TLR4 dimerization was determined by transfecting HEK293T cells with TLR4 plasmids. The in vivo anti‐inflammatory effect of isoacteoside was determined using mouse models of xylene‐induced ear oedema, LPS‐induced endotoxic shock and LPS‐induced endotoxaemia‐associated acute kidney injury (AKI).

Key Results

Isoacteoside suppressed COX‐2, iNOS, TNF‐α, IL‐6 and IL‐1β expression. Furthermore, isoacteoside attenuated the LPS‐induced transcriptional activity of NF‐κB by decreasing the levels of phosphorylated IκB‐α and IKK and NF‐κB/p65 nuclear translocation. In addition, isoacteoside inhibited LPS‐induced transcriptional activity of AP‐1 by reducing the levels of phosphorylated JNK1/2 and p38MAPK. Isoacteoside blocked LPS‐induced TLR4 dimerization, resulting in a reduction in the recruitment of MyD88 and TIR‐domain‐containing adapter‐inducing interferon‐β (TRIF) and the phosphorylation of TGF‐β‐activated kinase‐1 (TAK1). Pretreatment of mice with isoacteoside effectively inhibited xylene‐induced ear oedema and LPS‐induced endotoxic death and protected against LPS‐induced AKI.

Conclusions and Implications

Isoacteoside blocked TLR4 dimerization, which activates the MyD88–TAK1–NF‐κB/MAPK signalling cascades and TRIF pathway. Our data indicate that isoacteoside is a potential lead compound for the treatment of inflammatory diseases.

DOI10.1111/bph.13912
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000407420700007
PublisherWILEY
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Co-First AuthorGao, Hongwei
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.College ofPharmaceutical Science, Soochow University, Suzhou, China
3.Heilongjiang University of Chinese Medicine, Harbin, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Gao, Hongwei,Cui, Yankun,Kang, Naixin,et al. Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits anti-inflammatory effects through blocking toll-like receptor 4 dimerization[J]. BRITISH JOURNAL OF PHARMACOLOGY,2017,174(17):2880-2896.
APA Gao, Hongwei.,Cui, Yankun.,Kang, Naixin.,Liu, Xin.,Liu, Yanli.,...&Chen, Xiuping.(2017).Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits anti-inflammatory effects through blocking toll-like receptor 4 dimerization.BRITISH JOURNAL OF PHARMACOLOGY,174(17),2880-2896.
MLA Gao, Hongwei,et al."Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits anti-inflammatory effects through blocking toll-like receptor 4 dimerization".BRITISH JOURNAL OF PHARMACOLOGY 174.17(2017):2880-2896.
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