Title:Network Pharmacological Study of the Active Ingredient of Panax
Notoginseng Saponins for the Treatment of Lung Cancer by Inhibiting
AKR1C3
Volume: 21
Issue: 9
Author(s): Yue-Zi Wei, Mei-Zhu Yang and Wei Yuan*
Affiliation:
- School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China
Keywords:
Lung cancer, molecular docking, molecular target, network pharmacology, panax notoginseng saponins (PNS), signaling pathway.
Abstract:
Background: Lung cancer is the malignancy with the second highest diagnostic rate and the
leading cause of cancer-related death.
Objective: This study aims to investigate the potential mechanism and molecular targets of Panax notoginseng
saponins (PNS) in inhibiting lung cancer through network pharmacology.
Methods: Pharmacodynamic targets of each compound of PNS were searched from TargetNet, SwissTargetPrediction,
and BatMan-TCM databases. Next, the differential expression genes (DEGs) in
lung cancer were obtained from the Gene Expression Omnibus (GEO) database and screened by R
package. Later, the STRING 11.0 database was utilized to analyze the protein-protein interaction (PPI)
network of common targets of PNS-lung cancer, clusterProfiler to perform gene ontology (GO) annotation,
and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the
common targets, and Cytoscape 3.8.0 to construct and analyze the "ingredient-target" network for the
common targets of PNS-lung cancer.
Results: A total of 154 potential pharmacodynamic targets of PNS, 2399 DEGs of lung cancer-related
diseases, and 21 common targets of PNS-lung cancer were obtained by database search and screening.
The 21 common targets were mainly involved in biological processes (such as small molecule metabolism
and cytokine production) and were major components of cellular structures (such as neuronal cell
bodies and membrane rafts). Besides, these targets could function as carboxylic ester hydrolases, G
protein-coupled amine receptors, and oxidoreductase. They were mainly enriched in 14 signaling
pathways, like neuroactive ligand-receptor interaction, regulation of lipolysis in adipocytes, and calcium
signaling pathway. Furthermore, the molecular docking results revealed that aldo-keto reductase
family 1 member C3 (AKR1C3) and melanin metabolic enzyme (MME) may be direct targets of ginsenoside
Rg1 and notoginsenoside R2.
Conclusion: Our study showed that ginsenosides inhibit the progression of lung cancer through multiple
targets and pathways. More importantly, PNS may treat lung cancer by directly inhibiting AKR1C3.
