基于多技术整合网络药理学探究水红花子的药用潜力、物质基础及作用机制
Investigating the medicinal potential, material basis and mechanism of Polygoni Orientalis Fructus based on multi-technology integrated network pharmacology.
作者信息
Chen Kai, Qu Jianjiang, Chen Hongwei, Wang Jue, Hua Huilian, Li Jindong, Zhou Lei, Zhang Wei, Li Zheng
机构信息
Department of Pharmacy, The Hospital Affiliated to Medical School of Yangzhou University (Taizhou People's Hospital), Taizhou, China.
State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China.
出版信息
Phytomedicine. 2021 Oct;91:153685. doi: 10.1016/j.phymed.2021.153685. Epub 2021 Jul 25.
BACKGROUND
Polygoni Orientalis Fructus (POF) refers to the dried ripe fruit of Polygonum orientale L. which has a long historical application in clinic for treatment of various conditions in China. However, its chemical constituents, pharmacological effects and their coupled correlation have not been intensively investigated.
PURPOSE
In present work, we aimed to elucidate the medicinal material basis, optimum indication and corresponding therapeutic mechanism of POF.
METHODS
The main phytochemical ingredients in POF were characterized by liquid chromatography-mass spectrometry (LC-MS) analysis. The optimum medicinal potential and corresponding molecular mechanism of POF were deduced based on integrated statistic pattern recognition and network pharmacology. The deduced pharmacologic efficacy and mechanism of POF were further validated through in vitro study in free-fatty acid (FFA)-induced LO cells.
RESULTS
Total 30 main phytochemical ingredients were identified in POF in which 18 ingredients were screened to yield 277 potential targets. Based on analyzing the quantitative data matrix of drug-disease targets by statistic pattern recognition, non-alcoholic fatty liver disease (NAFLD) was screened as the optimum indication of POF from 23 candidate diseases. Promising action targets (PPARG, IL6, TNF, IL1B, IKBKB, RELA, etc.) and signaling pathways (AMPK signaling pathway, NF-κB signaling pathway, etc.) were screened and refined to elucidate the therapeutic mechanism of POF against NAFLD based on network pharmacology. In vitro study demonstrated that POF effectively alleviated FFA-induced steatosis, oxidative stress, mitochondrial dysfunction and inflammation, and these beneficial effects were attributed to the activation of AMPK signaling pathway and suppression of NF-κB signaling pathway.
CONCLUSION
POF could be exploited as a promising phytotherapy in the treatment of NAFLD.
背景
水红花子是蓼科植物红蓼干燥成熟果实，在中国临床长期应用于多种病症的治疗。然而，其化学成分、药理作用及其相互关联尚未得到深入研究。
目的
本研究旨在阐明水红花子的物质基础、最佳适应证及相应治疗机制。
方法
采用液相色谱 - 质谱联用（LC-MS）分析鉴定水红花子中的主要植物化学成分。基于综合统计模式识别和网络药理学推导水红花子的最佳药用潜力及相应分子机制。通过游离脂肪酸（FFA）诱导的LO2细胞体外研究进一步验证水红花子的药理作用及机制推导。
结果
共鉴定出水红花子中30种主要植物化学成分，筛选出18种成分，得到277个潜在靶点。通过统计模式识别分析药物 - 疾病靶点定量数据矩阵，从23种候选疾病中筛选出非酒精性脂肪性肝病（NAFLD）作为水红花子的最佳适应证。基于网络药理学筛选并优化了有前景的作用靶点（PPARG、IL6、TNF、IL1B、IKBKB、RELA等）和信号通路（AMPK信号通路、NF-κB信号通路等），以阐明水红花子抗NAFLD的治疗机制。体外研究表明，水红花子能有效减轻FFA诱导的脂肪变性、氧化应激、线粒体功能障碍和炎症，这些有益作用归因于AMPK信号通路的激活和NF-κB信号通路的抑制。
结论
水红花子有望开发成为治疗NAFLD的植物药。
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