基于文献分析及网络药理学探究柴芍六君子汤治疗卒中后抑郁共病失眠的作用机制OA

Objective This study systematically investigated the mechanisms of different fractions of Chaishao Liujunzi Decoction(CSLJZT)in treating post-stroke depression(PSD)comorbid with insomnia,based on literature analysis and network pharmacology.Methods CSLJZT was divided into groups according to traditional Chinese medicine(TCM)formulation principles.Active ingredients and potential targets of CSLJZT were screened using the TCMSP database.Disease-related targets for PSD comorbid with insomnia were predicted via GeneCards,OMIM,Disgenet,and TTD databases.Venn diagrams were used to identify overlapping targets between each herbal fraction and the disease.A"drug-active ingredient-target"network was constructed using Cytoscape,and protein-protein interaction(PPI)networks were analyzed to identify core targets.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to explore relevant biological processes and signaling pathways.Results According to TCM formulation theory,CSLJZT was divided into SGLQ group(Bupleurum,Paeonia lactiflora),JPYQ group(Ginseng,Poria,Atractylodes and Glycyrrhiza),HWHT group(Pinellia,Citrus reticulata)and the full CSLJZT group.The overlapping targets with the comorbid disease were 138,161,91,and 173,respectively.Key active ingredients included quercetin,kaempferol,β-sitosterol,7-methoxy-2-methyl isoflavone,nobiletin,isorhamnetin,biochanin A,formononetin,etc.Core targets included TP53,AKT1,JUN,STAT3,IL6,TNF,MAPK1/3,HSP90AA1,ESR1,BCL2,etc.Enrichment analysis indicated that SGLQ group,JPYQ group and full formula groups were mainly enriched in pathways such as lipid and atherosclerosis,and AGE-RAGE,collectively regulating neuroinflammation,apoptosis,and oxidative stress.In contrast,HWHT group was enriched in the neuroactive ligand-receptor interaction pathway,suggesting its role in modulating neurotransmitter homeostasis.Conclusion CSLJZT treats PSD comorbid with insomnia through an integrated multi-component,multi-target,multi-pathway mechanism.The SGLQ group and JPYQ group primarily exert anti-inflammatory,apoptosis-regulatory,antioxidant,and neurovascular regenerative effects via signaling pathways related to neuroinflammation,apoptosis,and oxidative stress.Meanwhile,HWHT group mainly regulates neurotransmitters to improve sleep,alleviate depression,and reduce inflammation.These findings validate the TCM treatment principle of"soothing the liver,strengthening the spleen,and harmonizing the stomach,"while elucidating its modern scientific basis.