Zhou Hailin, Wang Xuancheng, She Zhiyong, Huang Li, Wei Huijie, Yang Shanyi, Wei Zhijuan, Chen Hongwei, Yang Bao, Hu Zehua, Feng Xue, Zhu Pingchuan, Li Zijian, Shen Jiahui, Liu Huan, Dong Huanxiao, Chen Guanghui, Zhang Qisong
Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Guangxi, China.
College of Light Industry and Food Engineering, Guangxi University, Guangxi, China.
J Ethnopharmacol. 2024 Oct 28;333:118438. doi: 10.1016/j.jep.2024.118438. Epub 2024 Jun 6.
Hyperlipidemia as a major health issue has attracted much public attention. As a geographical indication product of China, Liupao tea (LPT) is a typical representative of traditional Chinese dark tea that has shown good potential in regulating glucose and lipid metabolism. LPT has important medicinal value in hyperlipidemia prevention. However, the active ingredients and metabolic mechanisms by which LPT alleviates hyperlipidemia remain unclear.
This study aimed to systematically investigate the metabolic mechanisms and active ingredients of LPT extract in alleviating hyperlipidemia.
Firstly, we developed a mouse model of hyperlipidemia to study the pharmacodynamics of LPT. Subsequently, network pharmacology and molecular docking were performed to predict the potential key active ingredients and core targets of LPT against hyperlipidemia. LC-MS/MS was used to validate the identity of key active ingredients in LPT with chemical standards. Finally, the effect and metabolic mechanisms of LPT extract in alleviating hyperlipidemia were investigated by integrating metabolomic, lipidomic, and gut microbiome analyses.
Results showed that LPT extract effectively improved hyperlipidemia by suppressing weight gain, remedying dysregulation of glucose and lipid metabolism, and reducing hepatic damage. Network pharmacology analysis and molecular docking suggested that four potential active ingredients and seven potential core targets were closely associated with roles for hyperlipidemia treatment. Ellagic acid, catechin, and naringenin were considered to be the key active ingredients of LPT alleviating hyperlipidemia. Additionally, LPT extract modulated the mRNA expression levels of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 associated with bile acid (BA) metabolism, mitigated the disturbances of BA and glycerophospholipid (GP) metabolism in hyperlipidemia mice. Combining fecal microbiota transplantation and correlation analysis, LPT extract effectively improved species diversity and abundance of gut microbiota, particularly the BA and GP metabolism-related gut microbiota, in the hyperlipidemia mice.
LPT extract ameliorated hyperlipidemia by modulating GP and BA metabolism by regulating Lactobacillus and Dubosiella, thereby alleviating hyperlipidemia. Three active ingredients of LPT served as the key factors in exerting an improvement on hyperlipidemia. These findings provide new insights into the active ingredients and metabolic mechanisms of LPT in improving hyperlipidemia, suggesting that LPT can be used to prevent and therapeutic hyperlipidemia.
高脂血症作为一个主要的健康问题已引起公众广泛关注。六堡茶（LPT）作为中国的地理标志产品，是中国传统黑茶的典型代表，在调节糖脂代谢方面显示出良好潜力。六堡茶在预防高脂血症方面具有重要药用价值。然而，六堡茶减轻高脂血症的活性成分和代谢机制仍不清楚。
本研究旨在系统探究六堡茶提取物减轻高脂血症的代谢机制及活性成分。
首先，我们建立高脂血症小鼠模型以研究六堡茶的药效学。随后，进行网络药理学和分子对接以预测六堡茶抗高脂血症的潜在关键活性成分和核心靶点。采用液相色谱 - 串联质谱法（LC-MS/MS）用化学标准品验证六堡茶中关键活性成分的身份。最后，通过整合代谢组学、脂质组学和肠道微生物组分析，研究六堡茶提取物减轻高脂血症的作用及代谢机制。
结果表明，六堡茶提取物通过抑制体重增加、纠正糖脂代谢失调和减轻肝损伤有效改善高脂血症。网络药理学分析和分子对接表明，四种潜在活性成分和七个潜在核心靶点与高脂血症治疗作用密切相关。鞣花酸、儿茶素和柚皮素被认为是六堡茶减轻高脂血症的关键活性成分。此外，六堡茶提取物调节了与胆汁酸（BA）代谢相关的Fxr、Cyp7a1、Cyp8b1和Cyp27a1的mRNA表达水平，减轻了高脂血症小鼠胆汁酸和甘油磷脂（GP）代谢的紊乱。结合粪便微生物群移植和相关性分析，六堡茶提取物有效改善了高脂血症小鼠肠道微生物群的物种多样性和丰度，特别是与胆汁酸和甘油磷脂代谢相关的肠道微生物群。
六堡茶提取物通过调节乳杆菌属和杜波氏菌属来调节甘油磷脂和胆汁酸代谢，从而改善高脂血症。六堡茶的三种活性成分是改善高脂血症的关键因素。这些发现为六堡茶改善高脂血症的活性成分和代谢机制提供了新见解，表明六堡茶可用于预防和治疗高脂血症。
