Distinct inhibitory mechanisms of isoquercitrin gallate and its aglycone on zymosan-induced peroxynitrite production in macrophages.
Peroxynitrite, the coupling product of superoxide and nitric oxide (NO) radicals, plays as a pathogenic mediator in the oxidative stress-implicated diseases. Quercetin 3-O-beta-(2''galloyl)-glucopyranoside (Q-32) is an isoquercitrin gallate. In this study, Q-32 was found to inhibit zymosan-induced production of protein-bound 3-nitrotyrosine, a stable metabolite of peroxynitrite, in macrophages RAW 264.7, and its inhibitory mechanism was also documented to be different from that of its aglycone, quercetin. Both Q-32 and quercetin inhibited not only zymosan- but also phorbol 12-myristate 13-acetate-induced superoxide productions in the macrophages. Q-32 did not affect NO production and inducible NO synthase (iNOS) expression in zymosan-stimulated macrophages RAW 2647. However, quercetin inhibited zymosan-induced NO production as well as down-regulated zymosan-induced iNOS expression at the transcription level. Further, quercetin inhibited zymosan-induced nuclear factor (NF)-kappaB transcriptional activity but also NF-kappaB-dependent iNOS promoter activity. Taken together, Q-32 and quercetin could provide invaluable tools to investigate zymosan-induced oxidative stress with distinct antioxidant mechanisms.
Kim
Byung-Hak
BH
College of Pharmacy & Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Lee
In Jeong
IJ
Lee
Hwa-Young
HY
Hwang
Bang Yeon
BY
Han
Sang-Bae
SB
Kim
Youngsoo
Y
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005707:Gallic Acid / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D051550:I-kappa B Kinase / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000737:chemistry; D011759:Pyrrolidines / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014162:Transfection; D015054:Zymosan / Q000494:pharmacology*
D000098:Acetophenones; D000975:Antioxidants; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C016527:isoquercitrin; D013481:Superoxides; D030421:Peroxynitrous Acid; C020972:pyrrolidine dithiocarbamic acid; D009569:Nitric Oxide; D005707:Gallic Acid; D015054:Zymosan; D011794:Quercetin; C085746:rottlerin; D008156:Luciferases; D052247:Nitric Oxide Synthase Type II; C497259:Prkcd protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; D051745:Protein Kinase C-delta; D013755:Tetradecanoylphorbol Acetate