Butanolides from Machilus thunbergii and their inhibitory activity on nitric oxide synthesis in activated macrophages.
In activated macrophages the inducible form of nitric oxide synthase (iNOS) generates high amounts of the toxic mediator, nitric oxide (NO), that contributes to the circulatory failure associated with septic shock. Three butanolides were isolated from Machilus thunbergii as active principles which inhibit the production of NO in lipopolysaccharide-activated RAW 264.7 cells, and their structures were identified as litsenolide A2 (1), B1 (2) and B2 (3). They showed dose-dependent inhibition of NO syntheses and the IC(50)s were 3.36, 3.70 and 6.19 micro m, respectively. These new inhibitors of iNOS may have potential in the treatment of endotoxaemia and inflammation accompanied by the overproduction of NO.
College of Pharmacy, Sookmyung Women's University, Chungpa-dong, Yongsan-gu, Seoul 140-742, Korea.
Nam Yi
NY
Kim
Jae-Ha
JH
Ryu
D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D006801:Humans; D019770:Lauraceae; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012772:Shock, Septic / Q000517:prevention & control*
D008070:Lipopolysaccharides; D010936:Plant Extracts; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II