Mechanism of Key Ingredient of <italic style="font-style: italic">Astragalus membranaceus</italic> on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation

WANG Yuan-chun; HUI Jian-rong; XIAO Gang; MA Qiao-lin

doi:10.1007/s11655-022-3681-x

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Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation

Original Article | Updated：2023-02-22

- Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation
- Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation
- 中国结合医学杂志（英文版） 2023年29卷第3期页码：244-252
- Affiliations：
  
  1.The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing (210023), China
  2.First Department of Oncology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province (712000), China
  3.College of Acupuncture-Moxibustion and Tuina, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province (712046), China
  4.First Department of General Surgery, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province (712000), China
- Author bio：
  
  Prof. WANG Yuan-chun, E-mail:yuanchun95@163.com
- Funds：
  
  the Scientific Research Project of the Affiliated Hospital of Shaanxi University of Chinese Medicine(2020MS016)
- DOI：10.1007/s11655-022-3681-x
  中图分类号：
- 纸质出版日期：2023-03，
  
  网络出版日期：2022-08-31，
  
  录用日期：2022-06-09
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Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation[J]. 中国结合医学杂志（英文版）, 2023,29(3):244-252.

WANG Yuan-chun, HUI Jian-rong, XIAO Gang, et al. Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation[J]. Chinese Journal of Integrative Medicine, 2023,29(3):244-252.
Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation[J]. 中国结合医学杂志（英文版）, 2023,29(3):244-252. DOI： 10.1007/s11655-022-3681-x.

WANG Yuan-chun, HUI Jian-rong, XIAO Gang, et al. Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation[J]. Chinese Journal of Integrative Medicine, 2023,29(3):244-252. DOI： 10.1007/s11655-022-3681-x.

摘要

Abstract

Objective:

To investigate the mechanism of the effect of

Astragalus membranaceus

(

A. membranaceus

) on lung adenocarcinoma at the molecular level to elucidate the specific targets according to the network pharmacology approach.

Methods:

The active components of

A. membranaceus

and their potential targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database. Lung adenocarcinoma-associated genes were acquired based on GeneCards

Online Mendelian Inheritance in Man (OMIM)

PharmGKB

and Therapeutic Targets databases. The PI3K/AKT signaling pathway-related genes were obtained using Reactome portal. Networks of "ingredient-target" and "ingredient-target-pathway-disease" were constructed using the Cytoscape3.6.0 software. The relationships among targets were analyzed according protein-protein interaction (PPI) network. Finally

molecular docking was applied to construct the binding conformation between active ingredients and core targets. Cell counting kit 8 (CCK8) and Western blot assays were performed to determine the mechanism of the key ingredient of

A. membranaceus

Results:

A total of 20 active components and their 329 targets

and 7

501 lung adenocarcinoma-related genes and 130 PI3K/AKT signaling pathway-related genes were obtained. According to Venn diagram and PPI network analysis

2 mainly active ingredients

including kaempferol and quercetin

and 6 core targets

including TP53

MAPK1

EGF

AKT1

ERBB2

and EGFR

were identified. The two important active ingredients of

A. membranaceus

kaempferol and quercetin

exert the therapeutic effect in lung adenocarcinoma partly by acting on the 6 core targets (TP53

MAPK1

EGF

AKT1

ERBB2

and EGFR) of PI3K/AKT signaling pathway. Expressions of potential targets in lung adenocarcinoma and normal samples were analyzed by using UALCAN portal and found that ERBB2 was overexpressed in lung adenocarcinoma tissues and upregulation of it correlated with clinicopathological characteristics. Finally

quercetin repressed viabilities of lung adenocarcinoma cells by targeting ERBB2 on PI3K/AKT signaling confirmed by CCK8 and Western blot.

Conclusion:

Our finding unraveled that an active ingredient of

A. membranaceus

quercetin

significantly inhibited the lung adenocarcinoma cells proliferation by repressing ERBB2 level and inactivating the PI3K/AKT signaling pathway.

关键词

Keywords

lung adenocarcinomacompound-target networkmechanism predictionmolecular dockingPI3K/AKT signaling pathwayChinese medicine

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Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation

DOI：10.1007/s11655-022-3681-x

摘要

Abstract

关键词

Keywords

references