PMID: Life Sci. 2021 Dec 15 ;287:119929. Epub 2021 Oct 29. PMID: 34743947 Abstract Title: CAPE-pNOameliorates diabetic brain injury through modulating Alzheimer's disease key proteins, oxidation, inflammation and autophagy via a Nrf2-dependent pathway. Abstract: AIMS: CAPE-pNO, 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-pNOon streptozotocin-induced diabetic brain injury in vivo and in vitro.MAIN METHODS: Biochemical 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 FINDINGS: First, CAPE-pNOcould rescue the diabetic brain atrophy and diminish CA1 and CA3 cells of hippocampus and cerebral cortex. Second, CAPE-pNOcould decrease Aβ and p-tau (S396) expression through anti-oxidation, anti-inflammation and autophagy induction in vivo. Last, CAPE-pNOcould down-regulate p-tau (S396) expression through Nrf2-related anti-oxidation mechanisms in vitro.SIGNIFICANCE: CAPE-pNOmay exert brain protection via Nrf2-dependent way in diabetes. Additionally, Nrf2 was capable of regulating p-tau (S396) expression that is critical to AD.
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