Experimental research of regulation of σmethoxyphenol-related compounds on the inflammatory cytokine expression.

σ甲氧基苯酚相关化合物调节炎症细胞因子表达的实验研究。

• 批准号: 15592133
• 负责人: MURAKAMI Yukio
• 金额: $ 2.24万
• 依托单位: Meikai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15592133/
• 关键词: Lipopolysaccharide; Methoxyphenol; Inflammatory cytokine; Cyclooxygenase-2; Dimer; Bond dissociation energy; Anti-inflammatory activity; Phenolic function; COX-2; BDE; P.gingivalis線毛; eugenol; dehydrodiisoeuenol; 抗酸化作用; BHA

Natural antioxidants, o-methoxyphenols such as eugenol (4-allyl-2-methoxyphenol) and isoeugenol (4-propenyl-2-methoxyphenol), which are components of clover oil, are commonly used as a flavoring agent in cosmetics and food products. These compounds show an anti-inflammatory effect but have adverse effects characterized by inflammatory and allergic reactions when they used at higher concentrations, possibly due to their prooxidant activity and consequent formation of reactive quinone methide intermediates. Their beneficial biological activity may be obtained by avoiding these adverse effects by lessening the potent oxidative activity of these compounds. Thus, we recently designed several synthetic dimers of eugenol, isoeugenol or ferulic acid to lessen the prooxidant activity induced by these monomers, and demonstrated that these dimeric compounds showed the reduced cytotoxicity due to the decrease in the radical production. These findings suggest that o-methoxyphenol dimers might act a … More s a potent inhibitor of inflammatory and allergic responses. However, the inhibitory mechanism of these compounds on inflammatory responses has still not been clarified in detail. In the present study, we examined the inhibitory effect of dimer compounds such as bis-eugenol, dehydrodiisoeugenol, and bis-ferulic acid, on the lipopolysaccharide (LPS)- induced inflammatory mediator expression in mouse macrophage cell line RAW264.7. Eugenol, isoeugenol, ferulic acid and isoferulic acid were purchased from Tokyo Kasei Co. ; hesperetin and hesperidin was from Sigma Chemical Co. ; o-vanilin was from Wako Chemical Co. Escherichia coli O111B4 LPS purchased from LBL Inc. LPS-induced inflammatory cytokine such as IL-1β, TNF-α, and mouse neutrophil chemoattractant KC and cyclooxygenase (COX)-2 expressions were strongly inhibited by these dimer compounds, but not by their parent monomers. In addition, other o-methoxyphenol compounds such as hesperetin, hesperidin, o-vanilin and isoferulic acid also inhibited LPS-induced COX-2 expression at higher concentrations. o-Methoxyphenol compounds which exhibited the COX-2 inhibitory effect at low concentrations possessed the moderate bond dissociation energy (BDE) value ; parameter to predict the effect of a phenol function. These observations suggest that dimerization of o-methoxyphenols, leading to a high level of phenolic function, may exhibit a potent anti-inflammatory and anti-carcinogenic action on the various inflammatory or neoplastic diseases, and also may be a useful tool for the discovery of effective NSAID-like compounds. Less

天然抗氧化剂，O-甲氧基酚，例如Eugenol（4-酰基-2-甲氧基）和异烯醇（4-丙烯基-2-甲氧基），它们通常用作化妆品和食品的调味剂。这些化合物表现出抗炎作用，但具有不良反应，其特征是炎症和过敏反应以较高的浓度使用，由于其耐药活性以及随之而来的形成反应性醌甲基中间体。可以通过减少这些化合物的潜在氧化活性来避免这些不良反应来获得其有益的生物学活性。因此，我们最近设计了丁香酚，等烯醇或阿魏酸的几种合成二聚体，以降低这些单体引起的鉴定活性，并证明这些二聚体化合物由于自由基产生的降低而显示出降低的细胞毒性。这些发现表明，O-甲氧基诺醇二聚体可能会采取A……更多的炎症和过敏反应的抑制剂。但是，这些化合物对炎症反应的抑制作用仍然尚未详细阐明。在本研究中，我们检查了二聚体化合物（例如Bis- eugenol，脱氢二烯醇和二氢化酚）对脂多糖（LPS）诱导的炎症介质在小鼠巨噬细胞系RAW264.7中诱导的炎症介质表达的抑制作用。 Eugenol，isougenol，阿魏酸和同型酸是从Tokyo Kasei Co.购买的。胃蛋白酶和黄质蛋白来自Sigma Chemical Co.； O-Vanilin来自Wako Chemic Co.从LBL Inc.购买的Escherichia o111b4 LPS。LPS诱导的炎性细胞因子，例如IL-1β，TNF-α和小鼠中性粒细胞化学吸收剂KC和环氧酶（Cox）-2表达式 - 通过这些dimernomers的抑制作用。此外，其他O-甲氧基酚化合物，例如硫代蛋白，硫代蛋白，O-vanilin和同型酸还抑制了LPS诱导的COX-2在较高浓度下的表达。在低浓度下暴露COX-2抑制作用的O甲氧基因化合物假定中等键解离能（BDE）值；参数预测酚功能的效果。这些观察结果表明，O-甲氧基诺酚的二聚化导致高水平的酚类功能，可能在各种炎症或肿瘤疾病上表现出潜在的抗炎和抗癌作用，并且也可能是发现有效NSAID类似NSAID类似的化合物的有用工具。较少的

项目成果

Kinetics of radical-scavenging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression.

• 发表时间: 2005-09
• 期刊: Anticancer research
• 影响因子: 2
• 作者: A. Hirata;Y. Murakami;Masao Shoji;Y. Kadoma;S. Fujisawa

Ferulic acid dimmer inhibits lipopolysaccharide-stimulated cyclooxygenase-2 expression in macrophages.

阿魏酸二聚体抑制巨噬细胞中脂多糖刺激的环氧合酶 2 表达。

• 发表时间: 2005
• 期刊: In vivo 19巻
• 作者: Atsushi Hirata;et al.
• 通讯作者: et al.

Kinetics of radical-scavemging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression.

橙皮素和橙皮苷自由基清除活性的动力学及其对 COX-2 表达的抑制活性。

• 发表时间: 2005
• 期刊: Anticancer Research 25巻・5号
• 作者: Hirata;A.;et al.
• 通讯作者: et al.

Dimerization, ROS formation, and biological activity of o-methoxyphenols

邻甲氧基苯酚的二聚、ROS 形成和生物活性

• 发表时间: 2005
• 期刊: Arch Immunol Ther Exp 53
• 作者: Seiichiro Fujisawa

Theoretical prediction of the relationship between phenol function and COX-2/AP-1 inhibition for ferulic acid-related compounds.

阿魏酸相关化合物的苯酚功能与 COX-2/AP-1 抑制之间关系的理论预测。

• 发表时间: 2005
• 期刊: In vivo 19巻・6号
• 作者: Murakami;Y.;et al.
• 通讯作者: et al.