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Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway
Nie X.1; Chen S.-R.2; Wang K.1; Peng Y.1; Wang Y.-T.2; Wang D.1; Wang Y.2; Zhou G.-C.1
2017
Source PublicationScientific Reports
ISSN2045-2322
Volume7Issue:1
Abstract

Andrographolide derivatives or analogs exhibit potent anti-inflammatory effects in several disease models through NF-κB activity. In this study, we synthesized different andrographolide derivatives and investigated their effects on the toll-like receptor (TLR)-induced production of pro-inflammatory cytokines. Among these compounds, 3b, 5a, and 5b inhibited both TNF-α/NF-κB and TLR4/NF-κB signaling pathways. Treatment with compounds 3b, 5a, and 5b and their structural analogs, 3a and 6b, suppressed the expression of pro-inflammatory cytokines upon the activation of TLR3 and TLR4 ligands. Compounds 3b and 5a, but not 3a, 5b, or 6b, inhibited the nuclear translocation of the NF-κB p65 subunit. Treatment with compounds 3b, 5a, 3a, 5b, and 6b attenuated the phosphorylation of p65 and IκBα. Compounds 6b suppressed the expression of the NF-κB p65 subunit. However, these compounds, except for 5b, did not affect the TLR9-induced NF-κB-independent production of the pro-inflammatory cytokines, TNF-α, and IFN-β. Compound 3b potentially protected mice from LPS-induced acute pulmonary inflammation through the inhibition of p65 phosphorylation and the decrease of serum pro-inflammatory cytokines and chemokine. Our study revealed a functional structure-activity relationship between andrographolide derivatives and innate immunity. We identified compound 3b as a potent immune suppressive agent with the potential to protect acute pulmonary infection. © 2017 The Author(s).

DOI10.1038/s41598-017-04673-x
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000404846300076
The Source to ArticleScopus
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Cited Times [WOS]:11   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorWang Y.; Zhou G.-C.
Affiliation1.School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu, 211816, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macau
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Nie X.,Chen S.-R.,Wang K.,et al. Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway[J]. Scientific Reports,2017,7(1).
APA Nie X..,Chen S.-R..,Wang K..,Peng Y..,Wang Y.-T..,...&Zhou G.-C..(2017).Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway.Scientific Reports,7(1).
MLA Nie X.,et al."Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway".Scientific Reports 7.1(2017).
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