Network Pharmacology and <italic style="font-style: italic">in vitro</italic> Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer

LI Jie; CHANG Jin-yuan; JIANG Zheng-long; YIN Yu-kun; CHEN Jia-yang; JIN Wei; LI Hao; FENG Li

doi:10.1007/s11655-022-3677-6

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Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer

Original Article | Updated：2023-02-22

- Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer
- Chinese Journal of Integrative Medicine Vol. 29, Issue 3, Pages: 233-243(2023)
- Affiliations：
  
  1.National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing(100021), China
  2.Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing(100029), China
- Author bio：
  
  Prof. FENG Li, E-mail: fengli663@126.com
- Funds：
- DOI：10.1007/s11655-022-3677-6
  CLC：
- Published：2023-03，
  
  Published Online：12 September 2022，
  
  Accepted：21 March 2022
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LI Jie, CHANG Jin-yuan, JIANG Zheng-long, et al. Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer. [J]. Chinese Journal of Integrative Medicine 29(3):233-243(2023)
DOI：

LI Jie, CHANG Jin-yuan, JIANG Zheng-long, et al. Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer. [J]. Chinese Journal of Integrative Medicine 29(3):233-243(2023) DOI： 10.1007/s11655-022-3677-6.

摘要

Abstract

Objective:

To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research.

Methods:

The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then

the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds

and the potential mechanism of key compounds on the main therapeutic targets was verified.

Results:

Totally 76 effective compounds of YSQTG were found

as well as 309 related targets

and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed

suggesting that quercetin

luteolin

wogonin

kaempferol and baicalein may be the most important compounds

while quercetin had higher degree value and degree centrality

which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network

the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene

interleukin-6

tumor necrosis factor

and RELA proto-oncogene. The results of cell function experiments

in vitro

showed that quercetin could inhibit proliferation

invasion

and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells

such as proliferation

cell cycle

and cell metastasis. A total of 357 quercetin interacting proteins were screened

and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway

MAPK signaling pathway

and nuclear factor kappa B (NF-κB) signaling pathway

etc. Quercetin

the key compound of YSQTG

had stronger binding activity by molecular docking. Pull-down assay confirmed that NF-κB was a quercetin-specific interaction protein

and quercetin could significantly reduce the protein level of NF-κB

the main therapeutic target.

Conclusion:

YSQTG can be multi-component

multi-target

multi-channel treatment of esophageal cancer

it is a potential drug for the treatment of esophageal cancer.

关键词

Keywords

network pharmacologyesophageal cancerYishen Qutong GranuleChinese medicinequercetinnuclear factor kappa B

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School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University

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Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer

DOI：10.1007/s11655-022-3677-6

摘要

Abstract

关键词

Keywords

references