Tea Research Institute, Guangdong Academy of Agricultural Sciences/Guangdong Key Laboratory of Tea Resources Innovation & Utilization, Guangzhou 510640, China.
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, P. R. China.
J Agric Food Chem. 2020 Mar 4;68(9):2673-2683. doi: 10.1021/acs.jafc.0c00148. Epub 2020 Feb 25.
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the leading cause of chronic liver diseases throughout the world. The deficit of pharmacotherapy for NAFLD calls for an urgent need for a new drug discovery and lifestyle management. Black tea is the most popular and functional drink consumed worldwide. Its main bioactive constituent theaflavin helps to prevent obesity-a major risk factor for NAFLD. To find new targets for the development of effective and safe therapeutic drugs from natural plants for NAFLD, we found a theaflavin monomer theaflavin-3,3'-digallate (TF3), which significantly reduced lipid droplet accumulation in hepatocytes, and directly bound and inhibited the activation of plasma kallikrein (PK), which was further proved to stimulate adenosine monophosphate activated protein kinase (AMPK) and its downstream targets. Taken together, we proposed that the TF3-PK-AMPK regulatory axis is a novel mechanism of lipid deposition mitigation, and PK could be a new target for NAFLD treatment.
非酒精性脂肪性肝病（NAFLD）正在迅速成为全球慢性肝病的主要病因。NAFLD 的药物治疗不足，迫切需要新的药物发现和生活方式管理。红茶是世界上最受欢迎和最具功能性的饮料。其主要生物活性成分茶黄素有助于预防肥胖——这是 NAFLD 的一个主要危险因素。为了从天然植物中寻找开发有效和安全治疗药物的新靶点，我们发现了一种茶黄素单体茶黄素-3,3'-二没食子酸酯（TF3），它能显著减少肝细胞中脂滴的积累，并直接结合并抑制血浆激肽释放酶（PK）的激活，进一步证明其能刺激单磷酸腺苷激活蛋白激酶（AMPK）及其下游靶点。综上所述，我们提出 TF3-PK-AMPK 调节轴是一种减轻脂质沉积的新机制，PK 可能是治疗 NAFLD 的一个新靶点。
