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通过网络药理学和实验验证探索平糖 5 号胶囊治疗非酒精性脂肪性肝病的作用机制。

Exploring the mechanism of PingTang No.5 capsule on nonalcoholic fatty liver disease through network pharmacology and experimental validation.

机构信息

Traditional Chinese Medicine research studio, The First Affiliated Hospital of Xiamen University, Xiamen 361000, China.

Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Center for Endocrine and Metabolic Diseases, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China.

出版信息

Biomed Pharmacother. 2021 Jun;138:111408. doi: 10.1016/j.biopha.2021.111408. Epub 2021 Mar 5.

DOI:10.1016/j.biopha.2021.111408
PMID:33684693
Abstract

PingTang No.5 capsule (PT5), a modified Traditional Chinese Medicine (TCM) formula of Zexie Decoction, is used to treat patients with lipid metabolism disorders in our hospital. The present study was designed to investigate the mechanisms of PT5 in treating non-alcoholic fatty liver disease (NAFLD). PT5 information including ingredients, pharmacological properties, and potential targets was obtained from TCM databases. The candidate targets of PT5 were predicted by network pharmacological analysis, and the possible pathway and mechanism were obtained from DAVID database, followed by experimental validation in NAFLD mice model treated with PT5. Total 328 compounds were selected using the threshold oral bioactivity (OB) > 30% or drug-likeness (DL) > 0.1 of pharmacology characteristic, and 1033 candidate targets obtained to construct the network analysis. The 113 targets were selected from the intersection between candidate targets of PT5 and NAFLD relative gene. These targets were evaluated in diabetic complications, cancer, Hepatitis B, Fluid shear stress and atherosclerosis, and TNF signaling pathway. TNF-α was the important factor in protein interaction analysis of STRING and involved in the lipid regulation and oxidative stress in NAFLD. When administrated to the NAFLD mice, PT5 reduced weight, blood fatty acids, decreased the adipocyte size, and improved the metabolism. Besides, the molecular verification of lipid metabolism increased and oxidative stress reduced that interpreted the mechanism of PT5 preventing liver cell from lipid accumulation and injury of NAFLD. These results presented PT5 have the potential therapy as an alternative treatment for NAFLD.

摘要

平唐 5 号胶囊(PT5)是泽泻汤的一种改良中药配方,用于治疗我院脂质代谢紊乱患者。本研究旨在探讨 PT5 治疗非酒精性脂肪性肝病(NAFLD)的机制。PT5 的信息包括成分、药理特性和潜在靶点,均从中药数据库中获得。通过网络药理学分析预测 PT5 的候选靶点,并从 DAVID 数据库获得可能的途径和机制,然后在 PT5 治疗 NAFLD 小鼠模型中进行实验验证。使用药理学特征的口服生物活性(OB)>30%或药物相似性(DL)>0.1 的阈值,选择了 328 种化合物,得到了 1033 种候选靶点,用于构建网络分析。从 PT5 和 NAFLD 相关基因的候选靶点的交点中选择了 113 个靶点。这些靶点在糖尿病并发症、癌症、乙型肝炎、流体切应力和动脉粥样硬化以及 TNF 信号通路中进行了评估。TNF-α是 STRING 蛋白质相互作用分析中的重要因素,参与 NAFLD 的脂质调节和氧化应激。当给予 NAFLD 小鼠时,PT5 减轻体重、降低血液脂肪酸、减少脂肪细胞大小并改善代谢。此外,脂质代谢的分子验证增加,氧化应激降低,解释了 PT5 防止肝细胞脂质积累和损伤的机制。这些结果表明 PT5 具有作为 NAFLD 替代治疗的潜力。

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