Prenylflavones from Psoralea corylifolia Inhibit Nitric Oxide Synthase Expression through the Inhibition of I-κB-α Degradation in Activated Microglial Cells(Pharmacognosy)

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The overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) switches the function of NO from a physiological neuromodulator to a neurotoxic effector in central nervous system (CNS) after brain injury. From the methanol extracts of Psoralea corylifolia, we purified two inhibitors of NO production in lipopolysaccharide (LPS)-activated microglia by activity guided purification along with two inactive compounds. The active compounds were identified as a chromenoflavanone [7, 8-dihydro-8-(4-hydroxyphenyl)-2, 2-dimethyl-2H, 6H-benzo-(1, 2-b:5, 4-b') dipyran-6-one](1) and 4-hydroxylonchocarpin (2). And the inactive two compounds were identified as bavachinin (3) and bavachalcone (4) by spectral analysis. The compound 2 was isolated first time from this plant. Compounds 1 and 2 inhibited the production of NO in LPS-activated microglia in a dose dependent manner (IC_<50>'s were 11.4, 10.2 μM, respectively). They also suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells at 10μM as observed in Western blot analysis and RT-PCR experiment. Furthermore they inhibited the degradation of I-κB-α in activated microglia. These results imply that compounds 1 and 2 can be lead compounds for the development of neuroprotective drug with the inhibitory activity of NO overproduction by activated microglial cells.
公益社団法人日本薬学会の論文
2005-12-01