Expression of inducible nitric oxide synthase by alpha-hederin in macrophages.
alpha-Hederin, a triterpene saponin, is reported to have antitumor activities; however, the mechanism underlying its therapeutic effects is not known. In this study, we examine the effects of alpha-hederin on the release of nitric oxide (NO) and the level of inducible nitric oxide synthase (iNOS) gene expression in mouse macrophages. alpha-Hederin elicited a dose-dependent increase in NO secretion. Reverse-transcription polymerase chain reaction showed that the increased NO secretion was due to an increase in iNOS mRNA. Transient expression assays with NF-kappa B binding sites linked to the luciferase gene revealed that the increased level of iNOS mRNA induced by alpha-hederin was mediated by the NF-kappa B transcription factor complex. These results demonstrate that alpha-hederin stimulates NO release and is able to upregulate iNOS expression through NF-kappa B transactivation, which may be a mechanism, whereby alpha-hederin elicits its biological effects.
Jeong
Hye Gwang
HG
Department of Pharmacy, College of Pharmacy Chosun University, Kwangju, South Korea. hgjeong@mail.chosun.ac.kr
Choi
Chul Yung
CY
D000818:Animals; D027922:Caprifoliaceae; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives*; D011112:Polymyxin B / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*
D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D012333:RNA, Messenger; D012503:Saponins; C010177:beta-hederin; D009569:Nitric Oxide; D009828:Oleanolic Acid; D019001:Nitric Oxide Synthase; D011112:Polymyxin B