Title:Exploring the Potential Mechanism of Action of Ursolic Acid against Gastric Cancer
and COVID-19 using Network Pharmacology and Bioinformatics Analysis
Volume: 29
Issue: 16
Author(s): Zhiyao Liu, Hailiang Huang*, Ying Yu, Yuqi Jia, Lingling Li, Xin Shi and Fangqi Wang
Affiliation:
- Department of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
Keywords:
COVID-19, gastric cancer, network pharmacology, ursolic acid, bioinformatics analysis, WGCNA.
Abstract:
Background: Patients with gastric cancer (GC) are more likely to be infected with 2019 coronavirus
disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the prognosis
is worse. It is urgent to find effective treatment methods.
Objective: This study aimed to explore the potential targets and mechanism of ursolic acid (UA) on GC and
COVID-19 by network pharmacology and bioinformatics analysis.
Methods: The online public database and weighted co-expression gene network analysis (WGCNA) were used
to screen the clinical related targets of GC. COVID-19-related targets were retrieved from online public databases.
Then, a clinicopathological analysis was performed on GC and COVID-19 intersection genes. Following
that, the related targets of UA and the intersection targets of UA and GC/COVID-19 were screened. Gene Ontology
(GO) and Kyoto Encyclopedia of Gene and Genome Analysis (KEGG) pathway enrichment analyses
were performed on the intersection targets. Core targets were screened using a constructed protein-protein interaction
network. Finally, molecular docking and molecular dynamics simulation (MDS) of UA and core targets
were performed to verify the accuracy of the prediction results.
Results: A total of 347 GC/COVID-19-related genes were obtained. The clinical features of GC/COVID-19 patients
were revealed using clinicopathological analysis. Three potential biomarkers (TRIM25, CD59, MAPK14)
associated with the clinical prognosis of GC/COVID-19 were identified. A total of 32 intersection targets of UA
and GC/COVID-19 were obtained. The intersection targets were primarily enriched in FoxO, PI3K/Akt, and
ErbB signaling pathways. HSP90AA1, CTNNB1, MTOR, SIRT1, MAPK1, MAPK14, PARP1, MAP2K1,
HSPA8, EZH2, PTPN11, and CDK2 were identified as core targets. Molecular docking revealed that UA
strongly binds to its core targets. The MDS results revealed that UA stabilizes the protein-ligand complexes of
PARP1, MAPK14, and ACE2.
Conclusion: This study found that in patients with gastric cancer and COVID-19, UA may bind to ACE2, regulate
core targets such as PARP1 and MAPK14, and the PI3K/Akt signaling pathway, and participate in antiinflammatory,
anti-oxidation, anti-virus, and immune regulation to exert therapeutic effects.
