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. Vitexin, a flavone C-glycoside (apigenin-8-C-(3-D-glucopyranoside) that belongs to the flavone subclass of flavonoids, has been shown to possess antioxidant and anti-ischemic properties; however, the putative protective effects of vitexin on the CCH need further investigation. In the current study, the role of vitexin and its underlying mechanism were investigated with permanent bilateral common carotid artery occlusion (2V0) in rats as well as mouse hippocampal neuronal (HT22) cells with oxygen and glucose deprivation/reoxygenation (OGDIR) injury model. The results demonstrated that vitexin improved cognitive dysfunction as well as alleviated pathological neuronal damage in hematoxylin plus eosin (HE) and TUNEL results. The decreased levels of exchange protein directly activated by cAMP 1 (Epacl), Epac2, Ras-associated protein 1 (Raps), and phospho-extracellular signal-regulated kinase (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 NOD-like receptor 3 (NLRP3), caspase-1, interleukin 1 beta (IL-1 beta), IL6, and cleaved caspase-3. In vitro, vitexin increased the expression of Epacl 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 piugiessing 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 in vivo and in vitro, which provides enlightenment for the protection of CCH injury.

Automated summary

Vitexin has shown protective effects on chronic cerebral hypoperfusion (CCH), improving cognitive dysfunction and alleviating pathological neuronal damage by regulating inflammation and cell signaling pathways in rats with CCH. This study provides insights into the potential therapeutic role of vitexin in protecting against CCH-related injuries.