Prenylflavones from Psoralea corylifolia inhibit nitric oxide synthase expression through the inhibition of I-kappaB-alpha degradation in activated microglial cells.
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.
Lee
Ming Hong
MH
College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Korea.
Kim
Jae Yeon
JY
Ryu
Jae-Ha
JH
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
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