Inhibition of nitric oxide production in RAW 264.7 cells by azaphilones from xylariaceous fungi.
The aim of this study was to discover a novel agent that suppresses nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) in RAW 264.7 cells. We carried out a screening test in fifteen azaphilone compounds, which were isolated from xylariaceous inedible mushrooms. The structure-activity relationship was discussed; accordingly, azaphilones were divided into five groups based on the functional groups attached to the main azaphilone backbone. Rubiginosin A, an azaphilone with an orsellinic acid moiety attached to the bicyclic azaphilone through an ester linkage, showed potential inhibitory activity. To clarify the mechanism involved, total RNA extraction, followed by RT-PCR for inducible nitric oxide synthase (iNOS) and finally electrophoresis on agarose gel were performed. These findings indicated that suppression of the LPS-induced NO production of rubiginosin A is due to the inhibition of iNOS protein synthesis.
Quang
Dang Ngoc
DN
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
Harinantenaina
Liva
L
Nishizawa
Takashi
T
Hashimoto
Toshihiro
T
Kohchi
Chie
C
Soma
Gen-Ichiro
G
Asakawa
Yoshinori
Y
D000818:Animals; D001203:Ascomycota / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology*; D001713:Biphenyl Compounds; D002460:Cell Line; D003864:Depression, Chemical; D004587:Electrophoresis, Agar Gel; D005609:Free Radicals / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D010851:Picrates / Q000378:metabolism; D010860:Pigments, Biological / Q000302:isolation & purification / Q000494:pharmacology*; D012331:RNA, Fungal / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship
D001565:Benzoates; D001578:Benzopyrans; D001713:Biphenyl Compounds; D005609:Free Radicals; D008070:Lipopolysaccharides; D010851:Picrates; D010860:Pigments, Biological; D012331:RNA, Fungal; C494154:azaphilone; C488884:rubiginosin A; D009569:Nitric Oxide; C004931:1,1-diphenyl-2-picrylhydrazyl; D052247:Nitric Oxide Synthase Type II