Sesquiterpene Coumarins from Ferula sinkiangensis Act as Neuroinflammation Inhibitors

Abstract

Neuroinflammation mediated by microglia cells plays a critical role in the development of Alzheimer's disease. To identify novel natural neuroinflammation inhibitors, a bioactivity-guided phytochemical research was performed on the traditional Chinese medicine "Awei", that exhibited a significant inhibitory effect on nitric oxide production in over-activated microglia cells. The research identified sixteen bioactive sesquiterpene coumarins (two new and fourteen known ones) in the effective extract of <i>Ferula sinkiangensis</i>. Further, the anti-neuroinflammatory activities in BV-2 microglial cells were evaluated by monitoring LPS-induced nitric oxide production. In conclusion, the major constituent, (3'<i>S</i>, 5'<i>S</i>, 8'<i>R</i>, 9'<i>S</i>, 10'<i>R</i>)-kellerin (1.5 %, w/w), should be responsible for the anti-neuroinflammatory effect exhibited by Awei. Furthermore, it might be a potential natural therapeutic agent for Alzheimer's disease. The research indicated moreover, that its primary mechanism is the inhibition of mRNA expression of the inflammatory cytokines nitric oxide, tumor necrosis factor-α, cyclooxygenase-2, interleukin-6 and interleukin-1<i>β</i>.