title: Prenylflavones from Psoralea corylifolia inhibit nitric oxide synthase expression through the inhibition of I-kappaB-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 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 microM, respectively). They also suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells at 10 muM as observed in Western blot analysis and RT-PCR experiment. Furthermore they inhibited the degradation of I-kappaB-alpha 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.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Korea.
authors.forename: Ming Hong
authors.initials: MH
authors.lastname: Lee
authors.forename: Jae Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology; D005591:Chemical Fractionation / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D047309:Flavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009387:Neoprene / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D029907:Psoralea / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C508226:4-hydroxylonchocarpin; C508225:7,8-dihydro-8-(4-hydroxyphenyl)-2,2-dimethyl-2H,6H-benzo-(1,2-b-5,4-b')dipyran-6-one; D001578:Benzopyrans; D047188:Chalcones; D004791:Enzyme Inhibitors; D047309:Flavones; D005419:Flavonoids; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D010936:Plant Extracts; C508227:bavachalcone; C016077:prenyl; D009387:Neoprene; D052247:Nitric Oxide Synthase Type II; C468752:bavachinin