Li Shu-di, Li Su-Ling, Liu Jiang-Kai, Wang Zhen, Yuan Pei-Pei
Henan University of Chinese Medicine Zhengzhou 450000, China.
the First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou 450000, China.
Zhongguo Zhong Yao Za Zhi. 2021 Oct;46(19):5080-5087. doi: 10.19540/j.cnki.cjcmm.20210713.401.
The present study explored the mechanism of action of Gynostemma pentaphyllum in the treatment of metabolism associa-ted fatty liver disease(MAFLD) by network pharmacology and molecular docking. The main active components and action targets of G. pentaphyllum were collected from TCMSP. Disease-related targets were obtained from GeneCards, OMIM and TTD, and the common targets of the three databases were screened out, which were converted to the genes with standard names by UniProt. The drug-disease common target genes were obtained through Venn tool and uploaded to STRING for the construction of the protein-protein interaction(PPI) network. Cytoscape was used to construct and analyze the drug-active component-common target-disease network. The gene ontology(GO) analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed on the common targets by DAVID. Pymol was adopted to perform molecular docking of active components and the common targets and predict their binding ability. Twenty-four active components(such as gypenosides, quercetin and sitosterol) of G. pentaphyllum were screened out. Ninety-two targets were obtained and 54 common targets were identified. Key targets included TNF, IL6, PTGS2, TP53, CCL2 and VEGFA. GO analysis on biological processes, molecular functions and cellular components and KEGG pathway analysis were performed, and the results indicated that NF-κB, PI3 K-Akt, TNF and HIF-1 signaling pathways were mainly involved. Molecular docking results showed that gypenosides and quercetin had a strong binding ability to TNF, IL6 and PTGS2. The findings of this study revealed that the therapeutic efficacy of G. pentaphyllum on MAFLD might be achieved by resisting inflammation and oxidative stress and improving insulin resistance, providing ideas and a theoretical basis for the development and application of G. pentaphyllum in the treatment of MAFLD.
本研究通过网络药理学和分子对接技术，探讨了绞股蓝治疗代谢相关脂肪性肝病（MAFLD）的作用机制。绞股蓝的主要活性成分和作用靶点从中药系统药理学数据库（TCMSP）中收集。疾病相关靶点从基因卡片数据库（GeneCards）、在线人类孟德尔遗传数据库（OMIM）和治疗靶点数据库（TTD）中获取，并筛选出三个数据库的共同靶点，通过通用蛋白质资源数据库（UniProt）将其转换为标准名称的基因。通过维恩工具（Venn tool）获得药物-疾病共同靶基因，并上传至STRING构建蛋白质-蛋白质相互作用（PPI）网络。利用Cytoscape构建并分析药物-活性成分-共同靶点-疾病网络。通过DAVID对共同靶点进行基因本体论（GO）分析和京都基因与基因组百科全书（KEGG）通路富集分析。采用Pymol对活性成分与共同靶点进行分子对接，并预测它们的结合能力。筛选出绞股蓝的24种活性成分（如绞股蓝皂苷、槲皮素和甾醇）。获得92个靶点，鉴定出54个共同靶点。关键靶点包括肿瘤坏死因子（TNF）、白细胞介素6（IL6）、环氧化酶2（PTGS2）、肿瘤蛋白p53（TP53）、趋化因子配体2（CCL2）和血管内皮生长因子A（VEGFA）。进行了生物学过程、分子功能和细胞成分的GO分析以及KEGG通路分析，结果表明主要涉及核因子κB（NF-κB）、磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）、肿瘤坏死因子（TNF）和缺氧诱导因子-1（HIF-1）信号通路。分子对接结果表明，绞股蓝皂苷和槲皮素与肿瘤坏死因子（TNF）、白细胞介素6（IL6）和环氧化酶2（PTGS2）具有较强的结合能力。本研究结果表明，绞股蓝对MAFLD的治疗作用可能是通过抗炎、抗氧化应激和改善胰岛素抵抗来实现的，为绞股蓝在MAFLD治疗中的开发和应用提供了思路和理论依据。
