Pinocembrin Protects Human Brain Microvascular Endothelial Cells against Fibrillar Amyloid-beta(1-40) Injury by Suppressing the MAPK/NF-kappa B Inflammatory Pathways

Cerebrovascular accumulation of amyloid-beta (A beta) peptides in Alzheimer's disease (AD) may contribute to disease progression through A beta-induced microvascular endothelial pathogenesis. Pinocembrin has been shown to have therapeutic effects in AD models. These effects correlate with preservation of microvascular function, but the effect on endothelial cells under A beta-damaged conditions is unclear. The present study focuses on the in vitro protective effect of pinocembrin on fibrillar A beta(1-40) (fA beta(1-40)) injured human brain microvascular endothelial cells (hBMECs) and explores potential mechanisms. The results demonstrate that fA beta(1-40)-induced cytotoxicity in hBMECs can be rescued by pinocembrin treatment. Pinocembrin increases cell viability, reduces the release of LDH, and relieves nuclear condensation. The mechanisms of this reversal from A beta may be associated with the inhibition of inflammatory response, involving inhibition of MAPK activation, downregulation of phosphor-IKK level, relief of I kappa B alpha degradation, blockage of NF-kappa B p65 nuclear translocation, and reduction of the release of proinflammatory cytokines. Pinocembrin does not show obvious effects on regulating the redox imbalance after exposure to fA beta(1-40). Together, the suppression ofMAPK and the NF-kappa B signaling pathways play a significant role in the anti- inflammation of pinocembrin in hBMECs subjected to fA beta(1-40). This may serve as a therapeutic agent for BMEC protection in Alzheimer's-related deficits.