Inhibitory effects of three bisbenzylisoquinoline alkaloids on lipopolysaccharide-induced microglial activation

Activation of microglial cells has been considered to be associated with various neurodegenerative diseases. In this study, three bisbenzylisoquinoline alkaloids (liensinine, neferine, and isoliensinine) were found to inhibit microglial activation induced by lipopolysaccharide (LPS). Liensinine, neferine, and isoliensinine suppressed the release of NO and cytokines (TNF-alpha, IL-1 beta, and IL-6) by LPS-activated microglial cells. Three alkaloids displayed direct NO-scavenging activity in SNP solution and reduced LPS-induced protein and mRNA expression of iNOS in microglial cells. Further studies revealed that liensinine, neferine, and isoliensinine blocked I kappa B alpha phosphorylation and degradation, as well as ROS production in LPS-activated microglial cells. In addition, three alkaloids showed direct scavenging activity against DPPH, . OH, and ONOO radicals. These results suggest that liensinine, neferine, and isoliensinine may have potential in the treatment of neurodegenerative diseases accompanied by microglial activation.