ReferenceID 362

Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits anti-inflammatory effects through blocking toll-like receptor 4 dimerization

Br J Pharmacol

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

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Reference Id
362
Evidence Id
16952
Core Evidence Id
16952
Source Reference Id
703
Herb2 Reference Id
HBREF001198
Subject Paper Key
HBIN031342_28616865
Pubmed Id
28616865
Doi
10.1111/bph.13912
Paper Title
Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits anti-inflammatory effects through blocking toll-like receptor 4 dimerization
Paper 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.
Journal
Br J Pharmacol
Publish Year
2017
Experiment Subject
mouse macrophages
Experiment Type
Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits anti-inflammatory effects through blocking toll-like receptor 4 dimerization
Bilingual Status
semi_complete