Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits anti-inflammatory effects through blocking toll-like receptor 4 dimerization
Gao, H; Li, Ji; Wang, C; Xu, QM; Chen, X; Cui, Y; Kang, N; Liu, Xin; Liu, Y; Zou, Yue; Zhang, Z; Li, X; Yang, S; ,
| HERO ID | 7069794 |
|---|---|
| In Press | No |
| Year | 2017 |
| Title | Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits anti-inflammatory effects through blocking toll-like receptor 4 dimerization |
| Authors | Gao, H; Li, Ji; Wang, C; Xu, QM; Chen, X; Cui, Y; Kang, N; Liu, Xin; Liu, Y; Zou, Yue; Zhang, Z; Li, X; Yang, S; , |
| Journal | British Journal of Pharmacology |
| Volume | 174 |
| Issue | 17 |
| Page Numbers | 2880-2896 |
| Abstract | BACKGROUND AND PURPOSEIsoacteoside (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 APPROACHThe expression of the NF-kappa B pathway, MAPK pathway, iNOS, TNF-alpha, IL-6 and IL-1 beta 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 RESULTSIsoacteoside suppressed COX-2, iNOS, TNF-alpha, IL-6 and IL-1 beta expression. Furthermore, isoacteoside attenuated the LPS-induced transcriptional activity of NF-kappa B by decreasing the levels of phosphorylated I kappa B-alpha and IKK and NF-kappa B/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 TIRdomain- containing adapter-inducing interferon-beta (TRIF) and the phosphorylation of TGF-beta-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 IMPLICATIONSIsoacteoside blocked TLR4 dimerization, which activates the MyD88-TAK1-NF-kappa B/MAPK signalling cascades and TRIF pathway. Our data indicate that isoacteoside is a potential lead compound for the treatment of inflammatory diseases. |
| Doi | 10.1111/bph.13912 |
| Pmid | 28616865 |
| Wosid | WOS:000407420700007 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |