Dioscin ameliorates cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via HMGB-1 inhibition.

Dioscin ameliorates cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via HMGB-1 inhibition.
Free Radic Biol Med. 2015 Mar 12;
Authors: Tao X, Sun X, Yin L, Han X, Xu L, Qi Y, Xu Y, Li H, Lin Y, Liu K, Peng J
Abstract
We previously reported the promising effect of dioscin against hepatic ischemia /reperfusion (I/R) injury, but its effect on cerebral I/R injury remains unknown. In this work, an in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) model and an in vivo middle cerebral artery occlusion (MCAO) model were used. The results indicated that dioscin clearly protected PC12 cells and primary cortical neurons against OGD/R insult and significantly prevented cerebral I/R injury. Further research demonstrated that dioscin-induced neuroprotection was accompanied by a significant inhibition in the expression and the nuclear to cytosolic translocation of HMGB-1, reflected by decreased TLR4 expression. Blockade of the TLR4/MyD88/ TRAF6 signaling pathway by dioscin inhibited NF-κB and AP-1 transcriptional activities, MAPK and STAT3 phosphorylation, and pro-inflammatory cytokine responses, and up-regulated the levels of anti-inflammatory factors. In addition, small interfering RNA (siRNA) and over-expressed genes of HMGB-1 and TLR4 were applied in vitro experiments, respectively, and the results further confirmed that diosicn showed an efficient neuroprotection because of its inhibiting effects o...

Source: Free Radical Biology and Medicine - March 12, 2015 Category: Biology Authors: Tao X, Sun X, Yin L, Han X, Xu L, Qi Y, Xu Y, Li H, Lin Y, Liu K, Peng J Tags: Free Radic Biol Med Source Type: research