Vitexin regulates EPAC and NLRP3 and ameliorates chronic cerebral hypoperfusion injury.

Chronic cerebral hypoperfusion (CCH), as a critical factor of chronic cerebrovascular diseases, has greatly influenced the health of patients with vascular dementia (VD). The putative protective effects of vitexin on the CCH need further investigations. In the current study, the role of vitexin and its underlying mechanism were investigated with permanent bilateral common carotid artery occlusion (2VO) in rats as well as HT22 cells with OGD/R injury model. The results demonstrated that vitexin improved cognitive dysfunction as well as alleviated pathological neuronal damage in HE and TUNEL results. The decreased levels of Epac1, Epac2, Rap1 and p-ERK were reversed by vitexin in rats with CCH. Furthermore, this study indicated that vitexin alleviated CCH-induced inflammation injuries by reducing the expression of NLRP3, Caspase-1, IL-1β, IL-6, and cleaved Caspase-3. In vitro, vitexin increased the expression of Epac1 and Epac2, decreased the activation of the NLRP3-mediated inflammation, and improved cell viability. Taken together, our findings suggest that vitexin can reduce the degree of the progressing pathological damage in the cortex and hippocampus and inhibit further deterioration of cognitive function in rats with CCH. Epac and NLRP3 can be regulated by vitexin, which provides enlightenment for the protection of CCH injury.