Background and Objective: 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 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 nuclear factor-κB (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 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 neurological deficits in rats.
Conclusion:
Therefore, our findings support that HSYA exerts anti-inflammatory effects by reprogramming
the TLR9 signalling pathway during treatment of acute cerebral ischaemia and reperfusion
injury.
Mechanisms of the anti-inflammatory effects of the natural secosteroids physalins in a model of intestinal ischaemia and reperfusion injury