소엽의 Nitric Oxide Synthase 저해활성 및 Peroxynitrite소거활성

Abstract

Nitric Oxide (NO), derived from L-arginine, is produced by two types of nitric oxide synthase (constitutive NOS: cNOS, inducible NOS: iNOS). The NO produced in large amounts by the iNOS is known to be responsible for the vasodilation and hypotension observed in septic shock and inflammation. The inhibitors of iNOS, thus, may be useful candidates for the treatment 'of inflammatory diseases accompanied by the overproduction of NO. In order to find new inhibitors of iNOS, we have performed intensive screening of medicinal herbs for the inhibitory activity of NO production in lipopolysaccaride (LPS)-activated macrophages. We found that the ethanol extract of Perillae herba showed strong inhibition of NO production in activated macrophages. The solvent fractions of Perillae herba not only inhibited the expression of iNOS at 20 ㎍/㎖, but also showed scavenging activity of peroxynitrite anion. From the activity guided column chromatography of the ethanol extract, luteolin was identified as an active compound that showed dose-dependent inhibition of NO synthesis in LPS-activated macrophages (IC50 value; 6.9 μM). Luteolin may be an useful candidate for the development of new drug to treat endotoxemia and inflammation accompanied by the overproduction of NO.