Zhang Yuanhao, Li Jianguo, Wang Zexin, Chen Jie, Zhao Maoyuan, Guo Cui, Wang Tingyao, Li Ruilin, Zhang Hebin, Ma Xiao, Wen Yueqiang, Zeng Jinhao, Efferth Thomas
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
Bazhong Hospital of Traditional Chinese Medicine, Bazhong, China.
Phytomedicine. 2025 Jul;142:156651. doi: 10.1016/j.phymed.2025.156651. Epub 2025 Apr 10.
Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant health concern worldwide, exhibiting an increasing incidence that necessitates immediate intervention. Epigallocatechin-3-gallate (EGCG) has shown significant pharmacological benefits for liver diseases, including NAFLD. However, its efficacy in this context has not been systematically evaluated.
This meta-analysis aimed to consolidate preclinical evidence on the effectiveness and mechanisms of EGCG in treating NAFLD.
We conducted a comprehensive literature search for preclinical studies from the inception of each database to April 2024, including Excerpta Medica Database, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and China Science and Technology Journal Database. These studies were manually screened based on predefined criteria. Data extraction was followed by pooled effect size calculations using Stata 16.0. A machine learning approach was also utilized to examine the temporal relationships among variables.
Seventeen studies, involving 293 animals, were analyzed. Our analysis indicates that EGCG significantly reduces ALT, AST, hepatic triglyceride, serum TG, hepatic TC, serum TC. The targets of EGCG may include antioxidants, regulation of lipid metabolism, anti-inflammation, improvement of insulin resistance, and inhibition of hepatic fibrosis. EGCG exerted its effects on NAFLD by modulating key signaling pathways, including PI3K/Akt/AMPK, TGF-β/Smad, Nrf2, NF-κB, and ROS/MAPK, highlighting its multifaceted mechanisms of action. The machine learning methods employed to ascertain the temporal relationship between the intervention and the outcome indicated that the optimal duration of the intervention was 10 to 15 weeks.
The efficacy of EGCG in treating NAFLD has been predicted within a time frame of 10-15 weeks. It may exert its effects primarily through the NF-κB and Nrf2 pathways, which regulate the ROS phenotype. EGCG may represent a promising target for the treatment of NAFLD.
非酒精性脂肪性肝病（NAFLD）已成为全球范围内一个重大的健康问题，其发病率不断上升，亟需立即干预。表没食子儿茶素-3-没食子酸酯（EGCG）已显示出对包括NAFLD在内的肝脏疾病具有显著的药理益处。然而，其在这方面的疗效尚未得到系统评估。
本荟萃分析旨在整合关于EGCG治疗NAFLD的有效性和机制的临床前证据。
我们对从每个数据库建立之初到2024年4月的临床前研究进行了全面的文献检索，包括医学文摘数据库、PubMed、科学引文索引数据库、考克兰图书馆、中国知网、万方和中国科技期刊数据库。这些研究根据预先设定的标准进行人工筛选。数据提取后，使用Stata 16.0计算合并效应量。还采用机器学习方法来研究变量之间的时间关系。
分析了17项研究，涉及293只动物。我们的分析表明，EGCG可显著降低谷丙转氨酶（ALT）、谷草转氨酶（AST）、肝脏甘油三酯、血清甘油三酯（TG）、肝脏总胆固醇（TC）、血清总胆固醇。EGCG的作用靶点可能包括抗氧化剂、脂质代谢调节、抗炎、改善胰岛素抵抗以及抑制肝纤维化。EGCG通过调节关键信号通路对NAFLD发挥作用，包括磷脂酰肌醇-3-激酶/蛋白激酶B/腺苷酸活化蛋白激酶（PI3K/Akt/AMPK）、转化生长因子-β/信号转导分子和转录激活因子（TGF-β/Smad）、核因子E2相关因子2（Nrf2）、核因子κB（NF-κB）以及活性氧/丝裂原活化蛋白激酶（ROS/MAPK），突出了其多方面的作用机制。用于确定干预与结果之间时间关系的机器学习方法表明，最佳干预持续时间为10至15周。
已预测EGCG在10至15周的时间范围内对治疗NAFLD有效。它可能主要通过调节ROS表型的NF-κB和Nrf2途径发挥作用。EGCG可能是治疗NAFLD的一个有前景的靶点。
