Zhongguo Zhong Yao Za Zhi. 2026 Apr;51(7):2019-2028. doi: 10.19540/j.cnki.cjcmm.20251216.901.
ABSTRACT
This study adopted an integrated strategy combining serum transitional component screening, network pharmacology prediction, and animal experiment verification to systematically explore the core active components and mechanism of action of Yinxing Yangnao Formula(YYF) in the treatment of vascular dementia(VD), aiming to provide solid experimental evidence for the modernization of this classical TCM prescription. With the use of ultra-high performance liquid chromatography-Orbitrap high-resolution mass spectrometry(UPLC-Orbitrap-HRMS), a total of 97 chemical components were identified from the YYF extract by combining accurate mass-to-charge ratio, characteristic fragmentation ions of MS/MS, comparison with reference standards, and matching with literature databases. Furthermore, 27 serum transitional components were captured through the analysis of YYF-containing serum from rats, which were inferred as the key material basis for the in vivo pharmacodynamic effects of YYF. The potential targets of the serum transitional components were predicted using the SwissTargetPrediction database, and VD-related disease targets were screened from authoritative databases including GeneCard, OMIM, and GEO with the keyword dementia vascular. A total of 275 common targets were obtained with the Jvenn online tool. The "drug-component-target-disease" network was constructed using Cytoscape 3.9.1 software, and core active components such as isoscopoletin, jaceosidin, catalpol, senkyunolide F, and bilobalide were screened out. The protein-protein interaction(PPI) network was constructed via the STRING database, identifying key regulatory targets including the phosphatidylinositol 3-kinase family, sarcoma, protein tyrosine phosphatase, non-receptor type 11, Janus kinase 2, and protein tyrosine kinase 2. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis revealed that the core targets were mainly enriched in biological processes such as oxidative stress, neurological function, and immune and inflammatory responses, involving phosphoinositide 3-kinase-protein kinase B(PI3K-Akt), mitogen-activated protein kinase(MAPK), and Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3) signaling pathways. Molecular docking results showed that bilobalide had a good binding effect with core targets. Verification experiments on VD rat models demonstrated that YYF might exert the therapeutic effect by alleviating oxidative stress through modulating the serum levels of superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), and malondialdehyde(MDA). This study preliminarily clarified the material basis, pharmacological effects, and underlying mechanism of YYF in the treatment of VD, providing a direction and basis for subsequent research on the complete regulatory chain of "drug-target-pathway-phenotype".
PMID:42392782 | DOI:10.19540/j.cnki.cjcmm.20251216.901