CAPE-pNO2 ameliorates diabetic brain injury through modulating Alzheimer's disease key proteins, oxidation, inflammation and autophagy via a Nrf2-dependent pathway

Abstract

AimsCAPE-pNO2, an active derivative of caffeic acid phenethyl ester, has been verified to exert protection of diabetic cardiomyopathy and diabetic nephropathy. The present study aims to explore the brain protection effects and potential mechanisms of CAPE-pNO2 on streptozotocin-induced diabetic brain injury in vivo and in vitro. Main methodsBiochemical indexes including triglyceride, total cholesterol, superoxide dismutase and malondialdehyde contents were detected. The histopathological structure of hippocampus and cerebral cortex were determined. Immunofluorescence and immunoblot methods were used to assess expression of oxidative stress, inflammation and autophagy pathway-related proteins of diabetic brain in vivo. Alzheimer's disease (AD)-associated key proteins were also checked in vivo. DCFH-DA assay, immunofluorescence and immunoblot methods were applied to verify the master role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in vitro. Key findingsFirst, CAPE-pNO2 could rescue the diabetic brain atrophy and diminish CA1 and CA3 cells of hippocampus and cerebral cortex. Second, CAPE-pNO2 could decrease Aβ and p-tau (S396) expression through anti-oxidation, anti-inflammation and autophagy induction in vivo. Last, CAPE-pNO2 could down-regulate p-tau (S396) expression through Nrf2-related anti-oxidation mechanisms in vitro. SignificanceCAPE-pNO2 may exert brain protection via Nrf2-dependent way in diabetes. Additionally, Nrf2 was capable of regulating p-tau (S396) expression that is critical to AD.