2025, Vol. 29 ›› Issue (8): 1751-1760

Based on UHPLC-QE-MS, network pharmacology, and molecular dynamics simulation to explore the mechanism of Panax notoginseng in treating osteoarthritis

Chen Yueping1, Chen Feng2, Peng Qinglin2, Chen Huiyi3, Dong Panfeng1     

Abstract: BACKGROUND: Our previous research found that Panax notoginseng can repair the morphological structure of bone cells, which has a good application prospect in the treatment of osteoarthritis, but the specific mechanism of Panax notoginseng is still unclear.
OBJECTIVE: To identify the main components of Panax notoginseng using ultra-high performance liquid chromatography-Q exactive-mass spectrometry (UHPLC-QE-MS), and to explore the mechanism of Panax notoginseng in the treatment of osteoarthritis by combining network pharmacology, molecular docking and molecular dynamics simulation.
METHODS: After identifying the main components of Panax notoginseng by UHPLC-QE-MS technology, the active components were screened by TCMSP database, and the targets of active components were found by TCMSP and Uniprot database. Osteoarthritis targets were screened out through disease databases. After the intersection of drug targets and disease targets, the protein-protein interaction network was constructed by importing STRING database and Cytoscape software, and the “active ingredient-action target” network was constructed to screen key active ingredients. Then the key targets were enriched and analyzed, and the key active components and key targets were verified by molecular docking. Finally, the results with the lowest binding energy were selected for molecular dynamics simulation.
RESULTS AND CONCLUSION: A total of 57 active components were identified in the solution of Panax Notoginseng, including 50 intersection targets of components and disease targets, 5 key active components (quercetin, ursodeoxycholic acid, kaempferol, naringenin and erythrocyanine), and 5 key targets (interleukin 6, matrix metalloproteinase 9, interleukin 1β, albumin and recombinant chemokine c-motif ligand 2). Gene ontology enriched 642 entries, among which 620 entries represent biological processes, 21 entries represent molecular functions, and 1 entry represents cellular components. Kyoto encyclopedia of genes and genomes analysis indicated 63 pathways, mainly including estrogen signaling pathway, interleukin 17 signaling pathway and hyperglycosylation end product-hyperglycosylation end product receptor signaling pathway. Molecular docking showed good binding activity of key active components and key targets. Molecular dynamics simulation indicated that the stable interaction between quercetin and matrix metalloproteinase 9. The composition of Panax notoginseng was comprehensively studied, and the material basis of its efficacy was preliminarily clarified. It was predicted that Panax notoginseng could play an anti-inflammatory, cartilage-protective, and immunomodulatory role in treating osteoarthritis through multiple components, targets, approaches and pathways.
Key words: Panax notoginseng, osteoarthritis, molecular dynamics simulation, mass spectrometry, molecular docking, network pharmacology