Exploring the mechanisms of the protective effect of Desmodium styracifolium(Osb.)Merr on cholestatic liver disease based on network pharmacology and in vitro experiments
ZHI Yue-ping
ZHANG Ke-feng
TANG Zi-xuan
ZHANG Zhi-yuan
GAO Ya
CAO Hou-kang
Abstract：Objective:To explore the potential targets and mechanisms of Desmodium styracifolium(Osb.)Merr extracts(DME)in alleviating cholestatic liver disease(CLD)using ultra-high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),network pharmacology,molecular docking,and in vitro experiments.Methods:After detecting DME components with UPLC-MS/MS,potential active ingredients were further checked and their potential targets were predicted using the databases(TCMSP,SwissTargetPrediction database).For predicting the targets of CLD,databases(OMIM,GeneCards,and other databases)were used to retrieve the clinical sample dataset and obtain the differential genes,and the data was screened to obtain the key targets.Molecular docking was used to analyze the binding interactions between the core targets and DME potential active ingredients,and these findings were validated through cell experiments.Results:UPLC-MS/MS analysis combined with TCMSP identified 26 potential active ingredients and 497 target proteins.Database searches identified 2 393 targets for CLD,and clinical sample analysis revealed 6 684 differential genes in adults and 6 519 in pediatrics,with an intersection of 50 genes.KEGG enrichment analysis and literature review identified bile secretion pathways relevant to CLD.Further analysis of differential genes in clinical samples pinpointed the key gene NR1H4[encoding farnesoid X receptor(FXR)protein].Molecular docking results indicated that seven ingredients had high binding affinity with FXR.The Surface plasmon resonance(SPR)technique results confirm that schaftoside,a potential active ingredient in DME,has the best affinity with FXR.Cell experiments demonstrated that DME treatment upregulated FXR protein expression.Conclusion:Potential active components in DME,such as schaftoside,glycitein,and isovitexin,can exert therapeutic effects on CLD by modulating the key target FXR in the bile secretion pathway.
Keywords：Desmodium styracifolium(Osb.)Merrcholestatic liver diseasenetwork pharmacologyUPLC-MS/MS
Publication Date：2025-09-30
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：12( 1985-1996 )