Prenylflavones from Psoralea corylifolia inhibit nitric oxide synthase expression through the inhibition of I-kappa B-alpha degradation in activated microglial cells

Abstract

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 in-jury. 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 I and 2 inhibited the production of NO in LPS-activated microglia in a dose dependent manner (IC50's were 11.4, 10.2 mu M, respectively). They also suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells at 10 mu M as observed in Western blot analysis and RT-PCR experiment. Furthermore they inhibited the degradation of I-kappa B-alpha in activated microglia. These results imply that compounds I and 2 can be lead compounds for the development of neuroprotective drug with the inhibitory activity of NO overproduction by activated microglial cells.