Systems Pharmacology-based Analysis of Anti-tumor Mechanism of <italic style="font-style: italic">Houttuynia cordata</italic>

Yuru ZHANG; Xuping TIAN; Zezhou ZHAO; Wei XIAO; Yonghua WANG

doi:10.13422/j.cnki.syfjx.20220819

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Systems Pharmacology-based Analysis of Anti-tumor Mechanism of Houttuynia cordata

更新时间：2022-09-01

- Systems Pharmacology-based Analysis of Anti-tumor Mechanism of Houttuynia cordata
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 14, Pages: 165-171(2022)
- 作者机构：
  
  1.石河子大学，新疆石河子 832000
  2.江苏康缘药业有限公司，江苏连云港 222000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20220819
  CLC： R285;R289;R22;R2-031;R33
- Published：20 July 2022，
  
  Published Online：13 May 2022，
  
  Received：28 February 2022，
- 稿件说明：
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张玉如,田旭萍,赵泽州等.基于系统药理学分析鱼腥草抗肿瘤作用机制[J].中国实验方剂学杂志,2022,28(14):165-171.

ZHANG Yuru,TIAN Xuping,ZHAO Zezhou,et al.Systems Pharmacology-based Analysis of Anti-tumor Mechanism of Houttuynia cordata[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(14):165-171.
张玉如,田旭萍,赵泽州等.基于系统药理学分析鱼腥草抗肿瘤作用机制[J].中国实验方剂学杂志,2022,28(14):165-171. DOI： 10.13422/j.cnki.syfjx.20220819.

ZHANG Yuru,TIAN Xuping,ZHAO Zezhou,et al.Systems Pharmacology-based Analysis of Anti-tumor Mechanism of Houttuynia cordata[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(14):165-171. DOI： 10.13422/j.cnki.syfjx.20220819.

摘要

目的

采用系统药理学的方法探讨鱼腥草治疗肺癌的有效成分、作用靶点及作用机制，为其进一步开发和临床应用提供参考。

方法

利用中药系统药理学数据库（TCMSP）筛选鱼腥草的化学成分；通过口服生物利用度（OB）、类药性（DL）两个药代动力学参数筛选活性化合物；接着进行靶点筛选并对靶点进行富集分析；最后，选取鱼腥草素钠（SH）进行分子层面抗肿瘤机制的验证，通过细胞增殖与毒性检测（CCK-8）实验评估SH对两种肺癌细胞系（A549，LLC）体外增殖的影响，并通过蛋白免疫印迹法（Western blot）验证SH对肿瘤相关蛋白的调节作用。

结果

首先筛选得到7个活性化合物，通过预测得出活性化合物对应的352个相关靶点；接着，通过对靶点的富集分析发现鱼腥草对于癌症有潜在的治疗作用；最终CCK-8结果显示，SH对A549与LLC均有抑制作用，Western blot结果显示，G

/S-特异性周期蛋白D

、E

（Cyclin D

，Cyclin E

）及细胞周期蛋白依赖性激酶2和激酶4（CDK2，CDK4）均有下调趋势，并且Janus激酶2（JAK2）和信号转导子与转录激活子3（STAT3）也变化明显。

结论

该研究发现鱼腥草具有潜在的抗肿瘤作用，其可能通过JAK2/STAT3通路将肿瘤细胞遏制于细胞周期G

期而发挥抗肿瘤作用。

Abstract

Objective

To explore the effective components， targets， and mechanism of

Houttuynia cordata

against lung cancer by means of systems pharmacology and further to provide a reference for the further development and clinical application of this medicinal.

Method

Chemical components of

H. cordata

were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the active components were screened based on oral bioavailability （OB） and drug-likeness （DL）. Then the potential targets were predicted， followed by enrichment analysis. Finally， sodium houttuyfonate （SH） was selected for verifying the anti-tumor mechanism. Cell counting kit-8 （CCK-8） assay was used to evaluate the effect of SH on the

in vitro

proliferation of two lung cancer cell lines： A549 and LLC， and the regulation of tumor-related proteins by SH was verified by Western blot.

Result

A total of 7 active compounds and 352 targets of the active components were screened out. According to the enrichment analysis of targets，

H. cordata

had potential therapeutic effects on cancer. SH had inhibitory effect on both A549 and LLC. Western blot results showed that G

/S-specific Cyclin D

， E

and cyclin-dependent kinase （CDK）2， CDK4 all tended to be down-regulated， and Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） also changed significantly.

Conclusion

H. cordata

has the potential anti-tumor effects by arresting the tumor cells in the G

phase through the JAK2/STAT3 pathway.

关键词

鱼腥草肺癌系统药理学细胞周期

Keywords

Houttuynia cordatalung cancersystems pharmacologycell cycle

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Systems Pharmacology-based Analysis of Anti-tumor Mechanism of Houttuynia cordata

DOI：10.13422/j.cnki.syfjx.20220819

摘要

Abstract

关键词

Keywords

references