Suppression of inducible nitric oxide synthase mRNA expression by tryptoquinone A.
Triptoquinone A (TQA), which is an anti-inflammatory constituent in plants, was studied for its suppressive effect on nitric oxide production by LPS. TQA significantly suppressed smooth muscle relaxation and increase in cyclic GMP levels by nitric oxide (NO) in an L-arginine-induced relaxation experiment. The mechanistic studies showed that TQA did not directly inhibit NO radicals and inducible nitric oxide synthase (iNOS) enzyme but suppressed IL-1 beta and iNOS mRNA expression by LPS. The suppression level of iNOS gene expression by TQA was comparable to that by dexamethasone. TQA may be a useful candidate for the development of a drug as a potent inhibitor of iNOS gene over-expression.
Niwa
M
M
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan. mniwa@ph.tokushima-u.ac.ip
Tsutsumishita
Y
Y
Kawai
Y
Y
Takahara
H
H
Nakamura
N
N
Futaki
S
S
Takaishi
Y
Y
Kondoh
W
W
Moritoki
H
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D001120:Arginine / Q000494:pharmacology; D001483:Base Sequence; D006152:Cyclic GMP / Q000378:metabolism; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010944:Plants; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D004224:Diterpenes; D007375:Interleukin-1; D007527:Isoenzymes; D012333:RNA, Messenger; D014665:Vasodilator Agents; C100591:triptoquinone A; D009599:Nitroprusside; D010656:Phenylephrine; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP