Inhibitory effect of oxycoumarins isolated from the Thai medicinal plant Clausena guillauminii on the inflammation mediators, iNOS, TNF-alpha, and COX-2 expression in mouse macrophage RAW 264.7.
In the present study, we investigated the inhibitory effect of the known oxycoumarins poncitrin (3), osthol (4), and xanthoxyletin (5), newly isolated from Clausena guillauminii (Rutaceae), together with the known carbazoles heptaphylline (1) and 7-methoxyheptaphylline (2) on inducible-nitric oxide synthase (iNOS) expression induced by lipopolysaccharide (LPS) and the NO generation in RAW 264.7 mouse macrophages. Isolation of active oxycoumarins was guided by Western blot analysis of iNOS protein expression. These oxycoumarins showed an inhibitory effect on iNOS protein expression at 10 microM. Further examination of the inhibitory effects of these compounds on inflammation mediators revealed that the synthesis of nitric oxide (NO) and the protein expression of tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase-2 (COX-2) were inhibited by 5. It was expected that these compounds show anti-inflammatory activities.
Nakamura
Tomonori
T
Department of Molecular Pharmacology and Pharmacotherapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan. chitoku@faculty.chiba-u.jp
Kodama
Naoko
N
Arai
Yu
Y
Kumamoto
Takuya
T
Higuchi
Yoshihiro
Y
Chaichantipyuth
Chaiyo
C
Ishikawa
Tsutomu
T
Ueno
Koichi
K
Yano
Shingo
S
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D054700:Clausena / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003374:Coumarins; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2