title: Selective inducible nitric oxide synthase suppression by new bracteanolides from Murdannia bracteata.
abstract: Murdannia bracteata has been used as a Taiwanese folk medicine for its anti-inflammatory properties. However, neither its active ingredients nor its anti-inflammatory actions are well defined. Nitric oxide (NO), overproduced by activated macrophages via inducible NO synthase (iNOS), is suggested to be a significant pathogenic factor in various inflammatory tissue injuries. In order to elucidate the anti-inflammatory actions of M. bracteata, the present study was designed to isolate its active constituents and examine its effects on iNOS in lipopolysaccharide (LPS)-activated macrophages. Two new hydroxybutenolides, bracteanolide A (1) and B (2), together with (+)-(R)-p-hydroxyphenyllactic acid (3) and isovitexin (4), were isolated and identified from M. bracteata by the NO production assay. All of the compounds inhibited NO production except 3. Their rank order of potency was 1>2>4. Among these, 1 significantly inhibited NO production, which is associated with its suppression on iNOS induction in a concentration-dependent manner, with an IC(50) of 33.27+/-0.86 microM. Nevertheless, isometric tension recordings in isolated endothelium-intact rat aorta revealed that 1-4 did not affect acetylcholine-induced endothelial NO-dependent relaxation, an index of endothelial NOS (eNOS) activity. The selective inhibition on iNOS provides a possible explanation for the anti-inflammatory use of M. bracteata.
authors: National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC.
authors: Guei Jane
authors: GJ
authors: Wang
authors: Shih Ming
authors: SM
authors: Chen
authors: Wei Chou
authors: WC
authors: Chen
authors: Yu Min
authors: YM
authors: Chang
authors: Tzong Huei
authors: TH
authors: Lee
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D034821:Commelinaceae / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005663:Furans; D010936:Plant Extracts; D014665:Vasodilator Agents; C521620:bracteanolide A; C521619:bracteanolide B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D000109:Acetylcholine