6-烷氧基香豆素和 7-烷氧基香豆素衍生物对 RAW264 细胞脂多糖/干扰素 γ 刺激产生的一氧化氮的抑制作用。

Inhibitory effects of 6-alkoxycoumarin and 7-alkoxycoumarin derivatives on lipopolysaccharide/interferon γ-stimulated nitric oxide production in RAW264 cells.

机构信息

Department of Materials Science and Technology, Faculty of Engineering, Gifu University, Japan.

出版信息

Biol Pharm Bull. 2012;35(6):963-6. doi: 10.1248/bpb.35.963.

DOI:10.1248/bpb.35.963

Abstract

Coumarin and its derivatives are well known for their anti-inflammatory and anti-oxidative effects. In this study, we synthesized 32 coumarin derivatives from commercially available 6-hydroxycoumarin (6HC) and 7-hydroxycoumarin (7HC) and examined their effects on lipopolysaccharide/interferon γ (LPS/IFNγ)-stimulated nitric oxide (NO) production in murine macrophage RAW264 cells. Among these derivatives, 6HC-8 (6-(3-phenylpropoxy)coumarin), 6HC-14 (6-(2-octynyloxy)coumarin), 7HC-14 (7-(2-octynyloxy)coumarin), and 7HC-16 (7-(3,5-dimethoxybenzyloxy)coumarin) markedly suppressed NO production at low concentration (25 µM). These synthesized coumarin derivatives also markedly inhibited inducible NO synthase (iNOS) protein and mRNA expression, as assessed by western blotting and quantitative real time-polymerase chain reaction (RT-PCR).

摘要

香豆素及其衍生物以其抗炎和抗氧化作用而闻名。在这项研究中，我们从市售的 6-羟基香豆素（6HC）和 7-羟基香豆素（7HC）合成了 32 种香豆素衍生物，并研究了它们对脂多糖/干扰素 γ（LPS/IFNγ）刺激的小鼠巨噬细胞 RAW264 细胞中一氧化氮（NO）产生的影响。在这些衍生物中，6HC-8（6-（3-苯丙氧基）香豆素）、6HC-14（6-（2-辛炔氧基）香豆素）、7HC-14（7-（2-辛炔氧基）香豆素）和 7HC-16（7-（3,5-二甲氧基苄氧基）香豆素）在低浓度（25 µM）时显著抑制了 NO 的产生。通过 Western blot 和定量实时聚合酶链反应（RT-PCR），这些合成的香豆素衍生物还显著抑制了诱导型一氧化氮合酶（iNOS）蛋白和 mRNA 的表达。