| 摘要: |
| 目的：探究脂康饮治疗非酒精性脂肪性肝病（NAFLD）的作用机制。方法：利用TCMSP和HERB数据库获得脂康饮的活性成分，通过SwissTargetPrediction平台预测脂康饮作用靶点，GeneCards、DisGeNET数据库收集疾病靶点，取药物和疾病靶点交集作用为脂康饮治疗NAFLD的潜在靶点。通过 STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络，使用DAVID数据平台进行基因本体（GO）功能、京都基因与基因组百科全书（KEGG）通路富集分析，AutoDock软件进行分子对接、Gromacs 2020.6_GPU软件进行分子动力学模拟验证。结果：获得脂康饮的有效成分140种，治疗NAFLD的作用靶点269个，PPI网络核心蛋白为白细胞介素-6（IL-6）、肿瘤坏死因子（TNF）、过氧化物酶体增生激活受体γ（PPARG），GO功能富集分析结果显示，生物过程(BP)主要包括RNA聚合酶Ⅱ启动子转录的调控、信号转导等，细胞组成（CC）包括胞质溶胶、细胞质等，分子功能（MF）涉及蛋白激酶活性、酶结合等，主要信号通路为糖脂代谢通路、炎症与氧化应激通路、肿瘤通路等。分子对接发现活性成分泽泻醇B及泽泻醇B乙酸酯、ω-羟基大黄素-8-甲醚、木犀草素、柚皮素与靶点基因编码蛋白之间的结合良好，为脂康饮治疗NAFLD的主要成分。分子动力学模拟结果表明泽泻醇B与TNF、PPARG易形成稳定复合物，为脂康饮治疗NAFLD的主要成分。结论：脂康饮主要通过调节糖脂代谢、减轻肝脏炎症及氧化应激、抑制肿瘤通路治疗NAFLD，为研究脂康饮的作用机制提供了新的研究思路。 |
| 关键词: 非酒精性脂肪性肝病 脂康饮 网络药理学 分子对接 分子动力学 |
| DOI： |
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| Mechanism of action of Zhikang decoction in treatment of nonalcoholic fatty liver disease：A study based on network pharmacology and molecular dynamics |
| GE Jiale,CHEN Bin |
| (The First Traditional Chinese Medicine Clinical College of Hunan University of Chinese Medicine，Changsha 410007，Hunan，China;The First Affiliated Hospital of Hunan University of Chinese Medicine，Changsha 410007，Hunan，China) |
| Abstract: |
| Objective：To investigate the mechanism of action of Zhikang decoction in the treatment of nonalcoholic fatty liver disease (NAFLD).Methods：TCMSP and HERB databases were used to obtain the active components of Zhikang decoction，and SwissTargetPrediction platform was used to predict the action targets of Zhikang decoction.GeneCards and DisGeNET databases were used to collect disease targets，and the action targets of the drug and the disease targets were intersected to obtain the potential targets of Zhikang decoction in the treatment of NAFLD.STRING database was used to construct a protein-protein interaction (PPI) network；DAVID data platform was used to perform gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis；AutoDock software was used to perform molecular docking，and Gromacs 2020.6_GPU software was used to perform molecular dynamics simulation and validation.Results：The above analyses obtained 141 effective constituents of Zhikang decoction and 269 action targets in the treatment of NAFLD，and the PPI network showed the core proteins of interleukin-6，tumor necrosis factor (TNF)，and peroxisome proliferator-activated receptor gamma.The GO functional enrichment analysis showed that the biological processes mainly included regulation of RNA polymerase II promoter transcription and signal transduction；cellular components included cytosol and cytoplasm；molecular function included protein kinase activity and enzyme binding.The main signaling pathways included the glucose and lipid metabolism pathway，the inflammation and oxidative stress pathway，and the tumor pathway.Molecular docking showed that the active components alisol B，alisol B acetate，questinol，luteolin，and naringenin had good binding activities to the proteins encoded by the targets genes and were the main components of Zhikang decoction in the treatment of NAFLD.Molecular dynamics simulation showed that alisol B could easily form a stable complex with TNF and PPARG，and therefore，it was the main component of Zhikang decoction in the treatment of NAFLD.Conclusion：Zhikang decoction exerts a therapeutic effect on NAFLD by regulating glucose and lipid metabolism，alleviating liver inflammation and oxidative stress，and inhibiting the tumor pathway，which provides new ideas for the research on the mechanism of action of Zhikang decoction. |
| Key words: nonalcoholic fatty liver disease Zhikang decoction network pharmacology molecular docking molecular dynamics |
