期刊
PLOS ONE
卷 9, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0094586
关键词
-
资金
- National Natural Science Foundation of China [81072650, 81373870]
Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid that is isolated from the Stephania Tetrandra. It is known to possess anti-inflammatory and immunomodulatory effects. We have shown that TET can effectively suppress the production of bacterial lipopolysaccharide (LPS)-induced inflammatory mediators, including cyclooxygenases (COXs), in macrophages. However, whether TET has an antinociceptive effect on LPS-induced hyperalgesia is unknown. In the present study, we investigated the potential antinociceptive effects of TET and the mechanisms by which it elicits its effects on LPS-induced hyperalgesia. LPS effectively evoked hyperalgesia and induced the production of PGE(2) in the sera, brain tissues, and cultured astroglia. TET pretreatment attenuated all of these effects. LPS also activated inhibitor of kappa B (I kappa B) kinase beta (IKK beta) and its downstream components in the I kappa B/nuclear factor (NF)-kappa B signaling pathway, including COX-2; the increase in expression levels of these components was significantly abolished by TET. Furthermore, in primary astroglia, knockdown of IKK beta, but not IKK alpha, reversed the effects of TET on the LPS-induced increase in I kappa B phosphorylation, P65 phosphorylation, and COX-2. Our results suggest that TET can effectively exert antinociceptive effects on LPS-induced hyperalgesia in mice by inhibiting IKK beta phosphorylation, which leads to the reduction in the production of important pain mediators, such as PGE(2) and COX-2, via the IKK beta/I kappa B/NF-kappa B pathway.
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