Exploring the mechanism of Jianpi Huatan recipe in protecting hepatocellular carcinoma based on network pharmacology

Caiyun Zhang; Hongjiao Xiang; Junmin Wang; Gaoxuan Shao; Peilun Ding; Ying Gao; Hanchen Xu; Guang Ji; Tao Wu

doi:10.1016/j.jep.2023.116676

Exploring the mechanism of Jianpi Huatan recipe in protecting hepatocellular carcinoma based on network pharmacology

J Ethnopharmacol. 2023 Dec 5:317:116676. doi: 10.1016/j.jep.2023.116676. Epub 2023 Jun 4.

Authors

Caiyun Zhang¹, Hongjiao Xiang², Junmin Wang², Gaoxuan Shao³, Peilun Ding², Ying Gao², Hanchen Xu³, Guang Ji⁴, Tao Wu⁵

Affiliations

¹ Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
² Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
³ Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
⁴ Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: jg@shutcm.edu.cn.
⁵ Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: tw827@shutcm.edu.cn.

PMID: 37279814
DOI: 10.1016/j.jep.2023.116676

Abstract

Ethnopharmacological relevance: Jianpi Huatan Recipe (JPHTR) is an effective prescription for delaying progression of hepatocellular carcinoma (HCC) provided by Longhua Hospital affiliated to Shanghai University of traditional Chinese Medicine, and it is consisted of nine traditional Chinese drugs, but the protective mechanism of JPHTR against HCC progression is unclear.

Aim of the study: To study the mechanism of JPHTR preventing the progression of HCC based on the network pharmacology.

Materials and methods: The chemical component and potential gene targets of JPHTR and the important gene targets of HCC were obtained by retrieving traditional Chinese medicine network pharmacology analysis system (TCMNPAS) database. The data obtained from the database are used to construct the drugs-chemical component-targets network and protein-protein interaction network by using Cytoscape software and STRING database. The potential targets of JPHTR and HCC targets were imported into TCMNPAS-related modules in order to obtain the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Finally, we used HCC rat model to verify the vital signaling pathways predicted by network pharmacology.

Results: A total of 197 potential compounds and 721 potential targets of JPHTR and 611 important gene targets of HCC were obtained. Through the experiment in vivo, it was found that JPHTR can reduce the serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, reduce the lipid droplets and inflammatory injury of liver tissue, and reduce the mRNA expression of Interleukin-6 (Il-6), Janus tyrosine Kinase2 (Jak2) and Forkhead box O3 (Foxo3) in FOXO pathway in the liver, thus delaying the development of HCC.

Conclusion: Through network pharmacology and rat experiments, it is preliminarily confirmed that JPHTR may delay the progression of HCC by regulating the expression of Il-6/Jak2/Foxo3 in FOXO signal pathway, which is expected to be a new therapeutic target for the protection of HCC.

Keywords: FOXO Signal pathway; Hepatocellular carcinoma; Il-6/Jak2/Foxo3; Jianpi Huatan recipe; Network pharmacology.

MeSH terms

Animals
Carcinoma, Hepatocellular* / drug therapy
Carcinoma, Hepatocellular* / genetics
China
Drugs, Chinese Herbal* / pharmacology
Drugs, Chinese Herbal* / therapeutic use
Interleukin-6
Liver Neoplasms* / drug therapy
Liver Neoplasms* / genetics
Medicine, Chinese Traditional
Molecular Docking Simulation
Network Pharmacology
Rats

Substances

Interleukin-6
Drugs, Chinese Herbal