Stroke is one of the leading causes of death and disability worldwide. NLRP3 inflammasome has an essential role in the neuropathology of stroke. Recent studies report that shifting the microglial M1 phenotype to the M2 phenotype protects against ischemic stroke. In the present study, the precise effects of Tranilast, a NLPR3 inflammasome inhibitor, on stroke were evaluated. We established a murine model of distal middle cerebral artery occlusion (dMCAO) and administered Tranilast to dMCAO‐induced stroke mice. The NLRP3 level, caspase 1 activity, and infarct volume stroke mice were measured. The sensorimotor function, pro‐inflammatory cytokine production, and M1/M2 marker expression were measured. The M1 phenotype was induced by treatment of BV2 microglia with lipopolysacharide and interferon γ, and these BV‐2 cells were further treated with Tranilast. The expression of CD16 and CD206 was monitored. dMCAO increased the NLRP3 expression and enhanced caspase 1 activity. Tranilast treatment significantly decreased the infarct volume, improved sensorimotor function, and suppressed the production of inflammatory cytokines in stroke mice. Moreover, Tranilast decreased the M1 marker level while promoting the expression of M2 markers. In summary, our findings suggest that Tranilast ameliorates ischemic stroke through stimulating M2 polarization of microglia.

Background: Cerebral infraction seriously affects the life quality of patients. Danshensu has been reported to have anti-inflammatory and vascular protective effects. However, the therapeutic function of Danshensu on cerebral vascular injury are still unclear. Methods: Middle cerebral artery occlusion (MCAO) was used to construct the cerebral infraction model. Wound healing and tube formation assays were used to evaluate the angiogenesis in vitro. Western blot assay was used to evaluate the activation of the PI3K/Akt/mTOR signaling pathway. The laser Doppler scanner measured the regional cerebral blood flow (rCBF) in the area around the infarction, and the adhesion removal test was used to measure the sensorimotor function. The Modified Neurological Severity Score was performed to evaluate the cognitive functions of mice. Results: Danshensu promoted the proliferation of bEnd.3 cells and angiogenesis in vitro. Danshensu upregulated the expression of VEGF through PI3K/Akt/mTOR signaling pathway in bEnd.3 cells. Danshensu improved rCBF restoration and attenuated the behavioral deficits in mice post-MCAo/R. Conclusion: Danshensu enhances angiogenesis by PI3K/Akt/mTOR/VEGF signaling in cerebral ischemic injury mice.