Oregonin inhibits lipopolysaccharide-induced iNOS gene transcription and upregulates HO-1 expression in macrophages and microglia.
Oregonin isolated from Alnus formosana is a diarylheptanoid derivative, which appears to have antioxidative and anti-inflammatory activities. In this study, our data demonstrated inhibitory actions of oregonin on the LPS-induced iNOS protein in RAW264.7 macrophages and BV-2 microglial cells. We also suggested that HO-1 induction by oregonin might contribute to this action. Oregonin is able to dose-dependently reduce NO production, iNOS protein and iNOS promoter activity stimulated by LPS in RAW264.7 and BV-2 cells. Oregonin also showed inhibition of LPS-mediated NF-kappaB promoter activity and DNA-binding ability, as well as p65 nuclear translocation and phosphorylation. However, oregonin had no effect on IKK activity. AP-1 promoter activity and p38 MAPK activation but not PKC, ERK and JNK activation induced by LPS were attenuated by oregonin. Accompanying with iNOS protein reduction, moreover, we found that oregonin was able to induce HO-1 protein level. Results using a CO donor, [Ru(CO)(3)Cl(2)](2) further showed the ability of CO in reduction of iNOS protein level induced by LPS through the blockade of NF-kappaB and AP-1. Taken together, these results provide new evidences into the anti-inflammatory actions of oregonin, which include the inhibition of iNOS gene transcription via suppressing transcriptional activity of NF-kappaB and AP-1, as well as the upregulation of anti-inflammatory molecule HO-1. The HO-1-derived CO may also be involved in the suppressive effect on iNOS gene regulation.
Lee
Cheng-Jui
CJ
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Lee
Shoei-Sheng
SS
Chen
Su-Chung
SC
Ho
Feng-Ming
FM
Lin
Wan-Wan
WW
D029661:Alnus / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D036381:Diarylheptanoids / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D036381:Diarylheptanoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; C409456:oregonin; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases