Hydroxysafflor yellow A reprograms TLR9 signalling pathway in ischaemic cortex after cerebral ischaemia and reperfusion.

Hydroxysafflor yellow A reprograms TLR9 signalling pathway in ischaemic cortex after cerebral ischaemia and reperfusion. CNS Neurol Disord Drug Targets. 2018 May 01;: Authors: Gong Z, Pan J, Li X, Wang H, He L, Peng Y Abstract Hydroxysafflor yellow A (HSYA) was reported to suppress inflammation in ischaemic microglia. However, the mechanism through which HSYA inhibits inflammation caused by cerebral ischaemia and reperfusion injury remains unknown. Here, we have mimicked acute cerebral ischaemia and reperfusion injury by subjecting male Sprague-Dawley (SD) rats to transient middle cerebral artery occlusion for 90 minutes and have demonstrated that toll-like receptor 9 (TLR9) was upregulated from day 3 after reperfusion, accompanied by the persistent activation of the pro-inflammatory NF-κB pathway from 6 hours to day 7. HSYA was injected intraperitoneally at a dose of 6 mg/kg per day, which activated TLR9 in microglia of ischaemic cortex at 6 hours after reperfusion and then obviously suppressed the NF-κB pathway from day 1 to day 7. Meanwhile, HSYA also activated the anti-inflammatory pathway through interferon regulatory factor 3 (IRF3) from day 1 to day 3. The anti-inflammatory effect of HSYA was partially reversed by TLR9-siRNA interference in primary microglia, which was stimulated by oxygen-glucose deprivation and reoxygenation treatment. The regulation of TLR9-mediated inflammation by HSYA was consistent with the recovery of...
Source: CNS and Neurological Disorders Drug Targets - Category: Drugs & Pharmacology Authors: Tags: CNS Neurol Disord Drug Targets Source Type: research