应用化学 ›› 2022, Vol. 39 ›› Issue (11): 1680-1692.DOI: 10.19894/j.issn.1000-0518.210566

• 研究论文 • 上一篇    下一篇

基于网络药理学及分子对接技术研究向海雁鹅血的抗肺癌活性成分

王兴玥1, 高冷1(), 戚良晨2(), 高晓晨(), 丁磊2, 戚译天2, 崔本海, 尉松瑶1, 李航1   

  1. 1.(长春工业大学化学与生命科学学院,长春 130012) 2. (吉林大学中日联谊医院,长春 130033 )
    3.长春中医药大学吉林省人参研究院,长春 130117) 4. (通榆县向海崔成大雁养殖有限公司,白城 137211
  • 收稿日期:2021-02-13 接受日期:2022-07-08 出版日期:2022-11-01 发布日期:2022-11-09
  • 通讯作者: 高冷,戚良晨,高晓晨
  • 基金资助:
    吉林省科技发展计划项目(20190304086YY);吉林省教育厅“十三五”科学技术项目(JJKH20200905KJ)

Study on Anti⁃Lung Cancer Active Ingredients from Blood of Xianghai Wild Goose Based on Network Pharmacology and Molecular Docking Technology

Xing-Yu WANG1, Leng GAO1(), Liang-Chen QI2(), Xiao-Chen GAO(), Lei DING2, Yi-Tian QI2, Ben-Hai CUI, Song-Yao YU1, Hang LI1   

  1. 1.School of Chemistry and Life Science,Changchun University of Technology,Changchun 130012,China
    2.China-Japan Friendship Hospital of Jilin University,Changchun 130033,China
    3.Jinlin Institute of Ginseng Science,Changchun University of Chinese Medicine,Changchun 130117,China
    4.Tongyu Xianghai Cuicheng Dayan Breeding Co. ,Ltd. ,Baicheng 137211,China
  • Received:2021-02-13 Accepted:2022-07-08 Published:2022-11-01 Online:2022-11-09
  • Contact: Leng GAO,Liang-Chen QI,Xiao-Chen GAO
  • About author:gao_xiaochen@hotmail
    liangchen62@sina.com
    3627670700@qq.com
  • Supported by:
    the Foundation:Science and Technology Development Project of Jilin Province(20190304086YY);the “13th Five?Year plan” Science and Technology Project of Education Department of Jilin Province(JJKH20200905KJ)

摘要:

对向海雁鹅血抗肺癌的活性成分、潜在作用靶点及信号通路进行研究,并应用分子对接技术探索其抗肺癌可能的作用机制。利用高效液相色谱-质谱联用技术(HPLC-MS/MS)分析向海雁鹅血活性物质的成分;采用网络药理学筛选靶点,分析信号通路,构建向海雁鹅血活性物质“成分-靶点-通路”网络;利用细胞增殖检测(CCK-8)细胞活力测定法检测向海雁鹅血提取物对4种人癌细胞活力影响;运用分子对接核心靶点与向海雁鹅血活性成分;实时定量聚合酶链反应检测(qPCR)检测向海雁鹅血提取物对人肺癌A549细胞p-AKT1的mRNA表达的影响。结果分析出Pro、H-Asn-Asp-Asp-Met-OH、Thr-Thr-Asn-Tyr-Thr-Asp、和Ala-Trp-Met-Asp-Phe-Val 4种向海雁鹅血活性成分;获得相关靶点258个,其中核心靶点46个;GO基因富集分析涉及AKT1、IL1BS、SRC等关键靶点;KEGG信号通路富集涉及癌症信号通路等;向海雁鹅血提取物对4种人癌细胞的细胞活力均有抑制,其中对人肺癌A549细胞的抑制效果最明显;向海雁鹅血活性成分的核心靶点与肺癌靶点相映射结果显示是通过AKT1、IL1BS、SRC等关键靶点起到抑制A549的作用;分子对接结果显示:H-Asn-Asp-Asp-Met-OH与ATK1的结合能最高;qPCR检测结果显示,向海雁鹅血提取物能够显著减低A549细胞p-AKT1的mRNA的含量水平。向海雁鹅血活性物质通过多靶点、多通路的形式诱导人肺癌A549细胞凋亡,为向海雁鹅血抗肺癌的活性物质研究与开发提供了新的思路和方向。

关键词: 向海雁鹅血, HPLC-MS/MS, 网络药理学, 分子对接

Abstract:

Potential targets and signal pathways of Xianghai wild goose blood against lung cancer are studied, and the possible mechanism of action of Xianghai wild goose blood against lung cancer is explored by molecular docking technology. High performance liquid chromatography-mass spectrometry (HPLC-MS/MS) is used to analyze the components of active substances in Xianghai wild goose blood. The target is screened by network pharmacology, the signal pathway is analyzed, and the “component-target-pathway” network of blood active substances in Xianghai wild goose is constructed. CCK-8 cell viability assay is used to detect the effect of Xianghai wild goose blood extract on the viability of 4 kinds of human cancer cells. Molecular docking of the core target and the active components of Xianghai wild goose blood is analyzed; QPCR is used to detect the effect of blood extract from Xianghai wild goose on p-AKT1 mRNA expression in human lung cancer A549 cells. Pro, H-Asn-Asp-Asp-Met-OH, Thr-Thr-Asn-Tyr-Thr-Asp, and Ala-Trp-Met-Asp-Phe-Val are identified. 258 related targets and 46 core targets were obtained. GO enrichment analysis involves AKT1, IL1BS, SRC and other key targets. KEGG signaling pathway enrichment involves cancer signaling pathway, etc. The extracts of Xianghai wild goose blood could inhibit the cell viability of 4 kinds of human cancer cells, among which the inhibition effect on Human lung cancer A549 cell is the most obvious. Molecular docking results show that H-Asn-Asp-Asp-Met-OH has the highest binding energy with ATK1. qPCR results show that Xianghai wild goose blood extract could significantly reduce the mRNA level of p-AKT1 in human lung cancer A549 cells. The active substance of Xianghai wild goose blood induces apoptosis of human lung cancer A549 cells through multi-target and multi-pathway, which provides a new idea and direction for the research and development of anti-lung cancer active substance of Xianghai wild goose blood.

Key words: Xianghai wild goose blood, HPLC-MS/MS, Network pharmacology, Molecular docking

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