Protective Effect of Artemisinin on Cerebral Ischemic Stroke Via PI3k/Akt/GSK-3ß Signaling Pathway Activation

In the present study effect of artemisinin was investigated in vitro on oxygen glucose-deprived BMECs and in vivo in cerebral ischemic stroke rat model. The results demonstrated that artemisinin treatment led to a significant (p < 0.05) decrease in caspase-3 activity in oxygen glucose-deprived rat BMECs. Exposure to artemisinin at 2.5 and 5 mu M concentrations effectively reversed oxygen glucose-deprivation mediated increase in LDH release in rat BMECs. Treatment of the cerebral ischemic stroke rats with artemisinin effectively increased the expression of p-PI3k, p-Akt and p-GSK3 ss proteins in rat brain tissues. Artemisinin treatment caused a significant (p <0.05) decrease in L-selectin, leptin, MCP-1 and TNFa cytokine production in cerebral ischemic stroke rat brain tissues. Treatment of the rats with artemisinin reversed cerebral ischemic stroke mediated suppression of synaptophysin, GAP-43 and MAP-2 expression in brain tissues. The O-atom of carbonyl group in artemisinin interacts with ARG (A: 849) amino acid residue of PI3k (1e7u) protein. In conclusion, artemisinin treatment inhibited ischemia mediated damage to oxygen glucose-deprived rat BMECs in vitro and targeted PI3k/Akt/GSK3 ss activation in vivo in rat model of cerebral ischemic stroke. It targeted production of inflammatory cytokines, up-regulated GAP-43, MAP-2 and synaptophysin expression rat model of cerebral ischemic stroke. Therefore, artemisinin may be developed as an effective chemotherapeutic agent for the treatment of cerebral ischemic stroke.