Activated microglia produces diverse neurotoxic factors such as nitric oxide (NO) and tumor necrosis factor-alpha that serve as apoptotic inducers resulting in various neurodegenerative diseases. The inhibition of microglia-derived NO production by inducible nitric oxide synthase (iNOS) has been reported to be beneficial in retarding neurodegenerative disorders. Three active lignans have been isolated from the flower buds of Magnolia fargesii by the bioassay-guided fractionation using lipopolysaccharide (LPS)-activated BV-2 microglial cell culture system. The structures of them were identified as kobusin (1), aschantin (2) and fargesin (3) by the analyses of spectroscopic data. They inhibited the production of NO by activated microglia. Their IC(50) values were 21.8 +/- 3.7, 14.8 +/- 2.5 and 10.4 +/- 2.8 microg/mL, respectively. They suppressed LPS-induced NF-kappaB activation and the expression of iNOS protein and mRNA. Furthermore, they showed scavenging activity of neurotoxic peroxynitrite that can be produced by NO and superoxide anion. These results imply that lignans from Magnolia fargesii might be beneficial for the treatment of neuro-inflammatory diseases through the inhibition of iNOS expression and peroxynitrite scavenging potential.
Copyright (c) 2009 John Wiley & Sons, Ltd.