Abstract:

Objective To analyze the potential therapeutic targets of Huangqin Tang in treatment of colorectal cancer （CRC） by network pharmacology and molecular docking techniques，and to clarify the related molecular mechanism. Methods The active component and target dataset for Huangqin Tang were constructed based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）；the CRC-disease related target dataset was built by Databases such as GeneCards， Online Mendelian Inheritance in Man （OMIM），and pharmacogenetics and Pharmacogenomics Knowledge Base （PharmGKB）. Drug-disease target intersect， Huangqin Tang herbal formula network， and protein-protein interaction （PPI） networks were built by R software， Cytoscape software， and STRING Database； Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis were conducted by R software and Metascape platform；molecular docking validation was performed with AutoDock and PyMOL software to assess the ligand-receptor binding. Results A total of 136 effective active components of Huangqin Tang were screened， and 242 potential targets were identified for treatment of CRC， including 18 core targets. Five core key targets closely related to CRC， identified through signaling pathway analysis， were protein kinase B1（AKT1）， mitogen-activated protein kinase 3 （MAPK3），proto-oncogene FOS，tumor protein p53 （TP53），and proto-oncogene MYC.The GO functional enrichment analysis results mainly involved various biological processes related to cellular stress responses. The KEGG signaling pathway enrichment analysis results showed that potential targets were highly enriched in the cancer pathway； further analysis on CRC core targets via KEGG signaling pathway revealed involvement primarily in pathways related to endocrine resistance， apoptosis， and epidermal growth factor receptor-tyrosine kinase inhibitor （EGFR-TKI） resistance. The molecular docking results showed that the active components of Huangqin Tang， including quercetin， kaempferol， baicalein， 7-methoxy-2-methyl isoflavone， and naringenin， were stably docked with AKT1， MAPK3， FOS， TP53， and MYC， and quercetin exhibited the best binding with AKT1. Conclusion The active components of Huangqin Tang can treat CRC through multi-target and multi-pathway. The core ligand quercetin and AKT1 may exert the therapeutic effect in CRC by regulating the phosphatidylinositol 3-kinase （PI3K）/AKT and mammalian target of rapamycin （mTOR） signaling pathways to influence the cell proliferation， differentiation， and apoptosis processes.

Key words: Huangqin Tang, Network pharmacology, Molecular docking, Colorectal neoplasm, Quercetin