Equol inhibits nitric oxide production and inducible nitric oxide synthase gene expression through down-regulating the activation of Akt.
In the present study, we report the inhibitory effect of equol on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) gene expression in murine macrophages. In vivo administration of equol (i.p.) attenuated NO production by peritoneal adherent cells isolated from lipopolysaccharide (LPS)-treated mice. Equol dose-dependently inhibited the LPS-induced production of NO in isolated peritoneal adherent cells and RAW 264.7 cells. The mRNA expression of iNOS was also blocked by equol in LPS-stimulated RAW 264.7 cells. Further study demonstrated that the LPS-induced activation of Akt was suppressed by equol in RAW 264.7 cells while the activation of ERK, SAPK/JNK and p38 MAP kinase was not affected. Equol also blocked LPS-induced NF-kappaB activation. Moreover, the LPS-induced NO production and NF-kappaB activation was inhibited by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase/Akt pathway, in RAW 264.7 cells. These results suggest that equol might inhibit NO production and iNOS gene expression, at least in part, by blocking Akt activation and subsequent down-regulation of NF-kappaB activity.
Kang
Jong Soon
JS
Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Taejon, Republic of Korea.
Yoon
Yeo Dae
YD
Han
Mi Hwa
MH
Han
Sang-Bae
SB
Lee
Kiho
K
Park
Song-Kyu
SK
Kim
Hwan Mook
HM
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D060754:Equol; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007529:Isoflavones / Q000494:pharmacology*; D008070:Lipopolysaccharides; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics; D048789:Phytoestrogens / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D007529:Isoflavones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D048789:Phytoestrogens; D012333:RNA, Messenger; D009569:Nitric Oxide; D060754:Equol; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases