Huang Mou-Tuan, Liu Yue, Ramji Divya, Lo Chih-Yu, Ghai Geetha, Dushenkov Slavik, Ho Chi-Tang
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA.
Mol Nutr Food Res. 2006 Feb;50(2):115-22. doi: 10.1002/mnfr.200500101.
Tea has been shown to possess several health beneficial properties primarily due to its polyphenolic content. The major polyphenolic compounds in black tea leaves are theaflavins (TFs) formed by oxidative coupling of catechins in tea leaves during its processing. In this paper, we report the characterization of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear inflammatory model and the inhibitory effects of major black tea TFs derivatives on this inflammation. In addition, the effect on inflammatory biomarkers, such as proinflammatory cytokines and arachidonic acid metabolites, are reported as well. A single topical application of TPA to ears of CD-1 mice induced a time- and dose-dependent increase in edema as well as formation of proinflammatory cytokine proteins interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in mouse ears. A single topical application of equimolar of black tea constituents (TF, theaflavin-3-gallate, theaflavin-3'-gallate, and theaflavin-3,3'-digallate) strongly inhibited TPA-induced edema of mouse ears. Application of TFs mixture to mouse ears 20 min prior to each TPA application once a day for 4 days inhibited TPA-induced persistent inflammation, as well as TPA-induced increase in IL-1beta and IL-6 protein levels. TFs also inhibited arachidonic acid (AA) metabolism via both cyclooxygenase (COX) and lipoxygenase pathways. This observation was substantiated by decreased amounts of AA metabolites prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels. Combined application of TF and sulindac, a nonsteroidal anti-inflammatory drug resulted a significant synergetic anti-inflammatory effect. Oral administration of TFs or the hot water extract of black tea leaves also significantly inhibited TPA-induced edema in mouse ears. In conclusion, proinflammatory cytokines, IL-1beta and IL-6, as well as the intermediated metabolites of AA, PGE2, and LTB4 are good biomarkers for inflammation. Black tea constituents, TF and its derivatives, had strongly anti-inflammatory activity in vivo which may be due to their ability to inhibit AA metabolism via lipoxygenase and COX pathways.
茶已被证明具有多种有益健康的特性，这主要归功于其多酚含量。红茶中的主要多酚化合物是茶黄素（TFs），它是在茶叶加工过程中由儿茶素氧化偶联形成的。在本文中，我们报告了12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）诱导的小鼠耳部炎症模型的特征以及主要红茶TFs衍生物对该炎症的抑制作用。此外，还报告了其对炎症生物标志物的影响，如促炎细胞因子和花生四烯酸代谢物。对CD - 1小鼠耳部单次局部应用TPA会导致水肿呈时间和剂量依赖性增加，以及小鼠耳部促炎细胞因子蛋白白细胞介素 - 1β（IL - 1β）和白细胞介素 - 6（IL - 6）的形成。单次局部应用等摩尔的红茶成分（TF、茶黄素 - 3 - 没食子酸酯、茶黄素 - 3'- 没食子酸酯和茶黄素 - 3,3'- 二没食子酸酯）可强烈抑制TPA诱导的小鼠耳部水肿。每天一次，在每次应用TPA前20分钟将TFs混合物应用于小鼠耳部，持续4天，可抑制TPA诱导的持续性炎症以及TPA诱导的IL - 1β和IL - 6蛋白水平升高。TFs还通过环氧化酶（COX）和脂氧合酶途径抑制花生四烯酸（AA）代谢。花生四烯酸代谢物前列腺素E2（PGE2）和白三烯B4（LTB4）水平降低证实了这一观察结果。联合应用TF和非甾体抗炎药舒林酸产生了显著的协同抗炎作用。口服TFs或红茶叶的热水提取物也显著抑制TPA诱导的小鼠耳部水肿。总之，促炎细胞因子IL - 1β和IL - 6以及花生四烯酸的中间代谢物PGE2和LTB4是炎症的良好生物标志物。红茶成分TF及其衍生物在体内具有强烈的抗炎活性，这可能是由于它们能够通过脂氧合酶和COX途径抑制花生四烯酸代谢。
