Analysis of the Pharmacodynamic Material Basis and Mechanism of Mingshi Formula in Myopia Control Based on UPLC-Q-TOF-MS Technology and Network Pharmacology

HOU Xinyue; WANG Jianquan; KANG Zefeng; LI Danyu; SUN Hongrui; WANG Lulu; YAN Xin; LIU Mengyu; SHANG Yuhui; SUN Jian

Abstract：Objective To explore the potential mechanism of Mingshi formula in preventing and controlling myopia through blood component analysis and network pharmacology.Methods Qualitative analysis of the major chemical components and blood components of Mingshi formula was conducted using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS).The targets of the blood components were predicted using databases.Relevant targets for myopia were obtained from the GeneCards and DrugBank databases.Protein-Protein Interaction(PPI)networks for the potential targets of Mingshi formula in preventing and controlling myopia were constructed using the String platform and Cytoscape software.Functional enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)metabolic pathway enrichment analysis were conducted on the intersected targets using the DAVID database.Finally,a"component-disease-pathway-target"network diagram was constructed using Cytoscape software for analysis.Results A total of 139 chemical components were identified from the compound formulation,including saponins,triterpenoic acids,xanthones,phenolic acids,etc.A total of 46 blood-absorbed components of"Mingshi formula"were detected,among which 10 were derived from Yuanzhi(Polygalae Radix),13 from Renshen(Ginseng Radix),8 from Danshen(Salviae Miltiorrhizae Radix),8 from Fuling(Poria),3 from Tianma(Gastrodiae Rhizoma),1 from Shichangpu(Acori Tatarinowii Rhizoma),2 from Shanyao(Dioscoreae Rhizoma),and 1 from other sources.A total of 74 core targets related to Mingshi Formula and myopia were screened out.Enrichment analysis revealed that the core targets participated in signaling pathways such as Janus-activated kinase(JAK)/Singal transducers and activators of transcription(STAT),phosphatidylinositol 3-kinase(PI3K)/threonine-protein kinase(AKT),vascular endothelial growth factor(VEGF),and mitogen-activated protein kinase(MAPK),as well as biological processes such as insulin resistance and inflammatory response regulation.Conclusion The Mingshi Formula may exert its effect in preventing and controlling myopia by regulating various biochemical pathways,including mammalian target of rapamycin(mTOR)/hypoxia inducible factor(HIF)-1α,JAK/STAT,MAPK,PI3K-AKT,cyclic adenosine monophosphate(cAMP),and VEGF,through the blood-borne saponins,alkaloids,organic acids,and other chemical components within its compound formula.It adjusted the levels of the inflammatory cytokine interleukin(IL)-6 and targets HIF-1,matrix metalloproteinase(MMP),transforming growth factor(TGF),insulin like growth factor(IGF),and other key molecules.This comprehensive action improves the local ischemic and hypoxic microenvironment,intervenes in scleral remodeling,modulates inflammatory responses,and regulates biological rhythms.