ABSTRACT
A methanol extract of the flowers of Mammea siamensis (Calophyllaceae) was found to inhibit nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells. From the extract, two new geranylated coumarins, mammeasins A (1) and B (2), were isolated together with 17 known compounds including 15 coumarins. The structures of 1 and 2 were determined on the basis of their spectroscopic properties as well as of their chemical evidence. Among the isolates, 1 (IC(50) = 1.8 µM), 2 (6.4 µM), surangins B (3, 5.0 µM), C (4, 6.8 µM), and D (5, 6.2 µM), kayeassamins E (7, 6.1 µM), F (8, 6.0 µM), and G (9, 0.8 µM), mammea A/AD (11, 1.3 µM), and mammea E/BB (16, 7.9 µM) showed NO production inhibitory activity. Compounds 1, 9, and 11 were found to inhibit induction of inducible nitric oxide synthase (iNOS). With regard to mechanism of action of these active constituents (1, 9, and 11), suppression of STAT1 activation is suggested to be mainly involved in their suppression of iNOS induction.
Subject(s)
Coumarins/pharmacology , Enzyme Inhibitors/pharmacology , Mammea/chemistry , Nitric Oxide Synthase Type II/antagonists & inhibitors , Animals , Cells, Cultured , Coumarins/chemistry , Coumarins/isolation & purification , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Flowers/chemistry , Mice , Molecular Structure , Nitric Oxide Synthase Type II/biosynthesis , Nitric Oxide Synthase Type II/metabolism , Stereoisomerism , Structure-Activity RelationshipABSTRACT
The methylene chloride-methanol (1 : 1) extract from the air-dried aerial parts of wild Pulicaria undulata collected in North Sinia, Egypt, showed inhibitory effects on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in RAW264.7 macrophages. From the extract, three new sesquiterpenes named 5α-hydroperoxyivalin, 8-epi-xanthanol, and 8-epi-isoxanthanol were isolated together with four known sesquiterpenes. The structure of each new sesquiterpenes was determined on the basis of physicochemical and chemical evidence. In addition, all the sesquiterpenoids significantly inhibited the production of NO. Ivalin (IC50=2.0 µM) and 2α-hydroxyalantolactone (1.8 µM) showed particularly strong inhibitory effects, but had strong cytotoxic effects as well. Furthermore, ivalin and 2α-hydroxyalantolactone concentration-dependently reduced inducible NO synthase (iNOS) protein levels in RAW264.7 cells.
