Suhexiang pills inhibit ischemia stroke via targeting miR-24–3p to promote the activation of Keap1/Nrf2 signaling pathway

Abstract

The incidence of ischemic stroke (IS) is increasing year by year in China and the world. Cerebral ischemia-reperfusion injury (CIRI) caused by blood flow restoration during treatment seriously affects the prognosis of the disease. Suhexiang pills (ShxP) is a traditional Chinese medicine prescription for the treatment of IS. Its composition is complicated and the mechanism by which it regulates IS remains unclear. In this study, a MicroRNA, miR-24–3p, was found to inhibit neuronal injury, inflammatory response and cell apoptosis induced by OGD/R stimulation through gain- and loss-function experiments. Consistently, miR-24–3p inhibits nerve damage, inflammatory activation, and apoptosis induced by t/MCAO surgery in vivo. Mechanically, miR-24–3p can inhibit Keap1 expression and activate the downstream Nrf2-HO-1 signaling pathway. More importantly, we found that ShxP administration can promote the expression of miR-24–3p in the OGD/R-stimulated neuron model. However, inhibition of miR-24–3p can reverse the protective effect of ShxP on OGD/R-stimulated neurons. On the one hand, this result proved the new function of miR-24–3p in regulating CIRI. On the other hand, it clarified the new mechanism of ShxP in inhibiting the progression of IS by promoting the expression of miR-24–3p. It provides a theoretical basis for the drug application of ShxP.