Suppression of inducible nitric oxide synthase by (-)-isoeleutherin from the bulbs of Eleutherine americana through the regulation of NF-kappaB activity.
Eleutherine americana Merr. et Heyne (Iridaceae) has been used as a folk medicine for the treatment of coronary disorders and wound-healing. In our previous phytochemical study, several pyranonaphthoquinoids, including (-)-isoeleutherin, were isolated from the bulbs of E. americana. Because inhibitors of inducible nitric oxide synthase (iNOS) might be useful as anti-inflammatory agents, we investigated the potential of pyranonaphthoquinoids to inhibit iNOS activity. We found that (-)-isoeleutherin inhibits lipopolysaccharide (LPS)-stimulated induction of nitric oxide (NO) in a dose-dependent manner (IC(50)=7.4 microM). Using western blots and reverse transcription-polymerase chain reaction, we showed that (-)-isoeleutherin suppresses the expression of iNOS protein and mRNA. In addition, (-)-isoeleutherin inhibited the expression of various cytokines such as interleukin-1beta and interferon-beta. Activation of the transcriptional activity of NF-kappaB by LPS was also inhibited by treatment with (-)-isoeleutherin, suggesting that (-)-isoeleutherin-mediated suppression of iNOS expression is associated with the regulation of transcription factor NF-kappaB. These findings suggest that (-)-isoeleutherin might be a novel anti-inflammatory agent, and that it may work by inhibiting NFkB activation in macrophages.
Song
Su-Hyun
SH
College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
Min
Hye-Young
HY
Han
Ah-Reum
AR
Nam
Joo-Won
JW
Seo
Eun-Kyoung
EK
Seoung Woo Park
Sang Hyung Lee
Sang Kook Lee
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D027621:Iridaceae / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005663:Furans; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009285:Naphthoquinones; D009569:Nitric Oxide; D016899:Interferon-beta; D052247:Nitric Oxide Synthase Type II; C529519:isoeleutherin