Molecular mechanisms of Tibetan medicine Sug-Mel-sum-thang in treating insomnia disorder:network pharmacology,molecular docking,and surface plasmon resonance

Background:The Tibetan medicine Sug-Mel-sum-thang(SMST)is often used to treat insomnia disorder(ID);however,the underlying mechanism remains unclear.In this study,network pharmacology prediction was conducted to analyze the molecular mechanisms of SMST in treating ID.Methods:The active ingredients of the three herbs used in SMST were obtained from the Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences.Chemistry Database[DB/OL].The chemical formulae of the active ingredients were downloaded from PubChem in canonical SMILES format.These were then imported into the SwissTargetPrediction platform to identify drug targets.ID targets were obtained from databases such as DrugBank,GeneCards,and DisGeNET.Potential targets of SMST for the treatment of ID were identified using the online Venny mapping platform.The potential target protein-protein interaction was constructed using the STRING platform,and the obtained protein-protein interaction information was imported into Cytoscape 3.7.1 for image optimization and core gene extraction and ClueGO in Cytoscape 3.7.1 was used for the enrichment analysis of potential targets.Cytoscape 3.7.1 was also used to construct the regulatory network of the Tibetan medicine compound target pathway and conduct a topological analysis.Results:The mechanism of action of SMST in the treatment of ID involved 72 compounds,including nerolidol,apigenin,luteolin,and piperine.The key targets identified were COMT,CNR1,AKT1,SLC6A4,TNF,CTNNB1,and CHRNA4.The enrichment analysis obtained 69 KEGG pathways,mainly related to Alzheimer’s disease,cAMP signaling pathway,serotonergic synapse,and other pathways.The core active ingredient molecule docked with the target to a higher degree.The results showed that the active ingredient exhibited good binding activity with the related targets.Some parts with good docking fractions were selected for surface plasmon resonance analysis.Conclusion:Various active components in SMST play a role in the treatment of ID by acting on key targets,such as COMT and CNR1,to regulate multiple signaling pathways.