Nitric oxide and prostaglandin E2 synthesis inhibitory activities of diarylheptanoids from the barks of Alnus japonica steudel.
Nine known diarylheptanoids (1-9) isolated from the barks of Alnus japonica were evaluated for their inhibitory activities on nitric oxide (NO) and prostagrandin E2 (COX-2) production in interferon-gamma (INF-gamma) and lipopolysaccharide (LPS)-activated RAW 264.7 cells in vitro. The NO and COX-2 levels were moderately reduced by the addition of compounds (1-9). Among these compounds, compounds 6 and 8 inhibited NO production in a dose dependent manner with an IC50 of 16.7 and 27.2 microg/mL, respectively (positive control, L-NMMA; 22.8 microg/mL), and compounds 6, 7, 8, and 9 reduced the COX-2 level in a dose dependent manner with an IC50 of 20.7, 25.7, 25.0, and 27.3 microg/mL, respectively (positive control, indomethacin; 26.2 microg/mL). An analysis of the structural activity relationship among these diarylheptanoids suggests that the presence of a keto-enol group in the heptane moiety or a caffeoyl group in the aromatic ring were important for the efficacy on the inhibitory activities of NO and COX-2 production.
Kim
Hyun-Jung
HJ
College of Pharmacy, Chung Ang University, Seoul 156-756, Korea.
Yeom
Seung-Hwan
SH
Kim
Min-Kee
MK
Shim
Jae-Geul
JG
Paek
In-Na
IN
Lee
Min-Won
MW
D029661:Alnus / Q000737:chemistry*; D002855:Chromatography, Thin Layer; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D036381:Diarylheptanoids / Q000302:isolation & purification / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D024301:Plant Bark / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D036381:Diarylheptanoids; D008070:Lipopolysaccharides; D013778:Tetrazolium Salts; D013844:Thiazoles; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C022616:thiazolyl blue; D015232:Dinoprostone