Suppressive effects of furonaphthoquinone NFD-37 on the production of lipopolysaccharide-inducible inflammatory mediators in macrophages RAW 264.7.
2-Methyl-2-(2-methylpropenyl)-2,3-dihydronaphthoquinone[2,3-b]furan-4,9-dione (NFD-37) is a synthetic furonaphthoquinone compound. In this study, we determined that NFD-37 could inhibit the lipopolysaccharide (LPS)-induced production of inflammatory mediators in macrophages RAW 264.7. This compound inhibited LPS-induced nitric oxide (NO) or prostaglandin (PG) E2 production in dose-dependent manners, with IC50 values of 7.2 microM and 5.3 microM, respectively. As the positive controls, pyrrolidine dithiocarbamate (30 microM) exhibited a 57% inhibition of NO production, and NS-398 (1 microM) manifested a 48% inhibition of PGE2 production. The inhibitory effects of NFD-37 on NO and PGE2 production were determined to occur in conjunction with the suppression of inducible NO synthase or cyclooxygenase-2 expression. NFD-37 also inhibited the production of LPS-inducible tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6, at IC50 values of 4.8-8.9 microM. We also determined the anti-inflammatory efficacy of NFD-37 using carrageenin-induced paw edema in experimental mice.
Kim
Min-Hee
MH
College of Pharmacy & Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea.
Shin
Hyun-Mo
HM
Lee
Yong Rok
YR
Chung
Eun Yong
EY
Chang
Yoon Sook
YS
Min
Kyung Rak
KR
Kim
Youngsoo
Y
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C505240:2-methyl-2-(2-methylpropenyl)-2,3-dihydronaphtho(2,3-b)furan-4,9-dione; D005663:Furans; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009285:Naphthoquinones; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone