Wilfordonols A-D: four new norsesquiterpenes from the leaves of Tripterygium wilfordii.

Four new norsesquiterpenes wilfordonols A-D (1-4), along with three known compounds, sarmentol B (5), boscialin (6), and (+)-loliolide (7), were isolated from the leaves of Tripterygium wilfordii Hook.f.. The structures of the new compounds were elucidated on the basis of their spectroscopic analysis, and the absolute configuration of the compounds was confirmed by CD and modified Mosher's method. At a concentration of 10 µM, compounds 4, 6, and 7 inhibited signal transducer and activator of transcription 1 translocation by 34.27 ± 1.02%, 48.93 ± 1.76%, and 70.31 ± 2.20%, respectively.

Pinocembrin protects human brain microvascular endothelial cells against fibrillar amyloid-ß(1-40) injury by suppressing the MAPK/NF-κB inflammatory pathways.

Cerebrovascular accumulation of amyloid-ß (Aß) peptides in Alzheimer's disease (AD) may contribute to disease progression through Aß-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 Aß-damaged conditions is unclear. The present study focuses on the in vitro protective effect of pinocembrin on fibrillar Aß(1-40) (fAß(1-40)) injured human brain microvascular endothelial cells (hBMECs) and explores potential mechanisms. The results demonstrate that fAß(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 Aß may be associated with the inhibition of inflammatory response, involving inhibition of MAPK activation, downregulation of phosphor-IKK level, relief of IκBα degradation, blockage of NF-κB 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 fAß(1-40). Together, the suppression of MAPK and the NF-κB signaling pathways play a significant role in the anti-inflammation of pinocembrin in hBMECs subjected to fAß(1-40). This may serve as a therapeutic agent for BMEC protection in Alzheimer's-related deficits.