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-β-(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)-κB transcriptional activity but also NF-κB-dependent iNOS promoter activity. Taken together, Q-32 and quercetin could provide invaluable tools to investigate zymosan-induced oxidative stress with distinct antioxidant mechanisms.