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.

Insomnia is associated to depressive symptoms in patients with chronic heart failure

Introduction: Insomnia and depressive symptoms are common among patients with chronic heart failure (HF). Aim: The aim was to describe the prevalence of insomnia and depressive symptoms, as well as to examine the association between insomnia and depressive symptoms in patients with HF. Method: A crosssectional descriptive study including 212 patients with HF. All patients responded to questionnaires regarding sleeping difficulties (Uppsala Sleep Inventory-Chronic Heart Failure), daytime sleepiness (Epworth Sleepiness Scale) and depressive symptoms (The Mental Health Scale). Results: Patients with depressive symptoms (34%) had, compared to those without, significantly more major complaints of insomnia as indicated by the sub-types;non-restorative sleep (66% vs. 32%, p < 0.0001), difficulty in maintaining sleep (35% vs. 16%, p = 0.003), difficulty in initiating sleep (29% vs. 14%, p = 0.009) and early morning awakenings (25% vs. 10%, p = 0.004). The odds ratio (OR) to suffer from depressive symptoms;were for;non-restorative sleep 5.2 (CI 95%, 2.2 - 12.3), difficulties maintaining sleep 2.5 (CI 95%, 1.2 - 4.9), difficulties in initiating sleep 2.2 (CI 95%, 1.1 - 4.4) and early morning awakenings 2.4 (CI 95%, 1.1 - 5.4). When categorising insomnia into three severity groups, 1) non insomnia, 2) mild insomnia, and 3) severe insomnia, the OR for depressive symptoms for the mild insomnia and severe insomnia group were 2.2 (CI 95%, 1.1 - 4.2) and 7.4 (CI 95%, 2.4 - 22.8) respectively, compared to the non insomnia group. Conclusion: Insomnia is independently associated to depressive symptoms. Assessment of depressive symptoms and insomnia in patients with HF is important since treatment could be targeted to depressive symptoms only and/or to the sleep disturbance.

Progress in the correlation between chronic insomnia disorder and cytokines

Chronic insomnia disorder(CID)is a relatively common clinical sleep disorder,which is es-sentially characterized by dissatisfaction with sleep due to frequent and persistent difficulties in falling asleep or maintaining sleep.The etiology and pathogenesis of CID are not fully understood.In the past decades,medical re-search has explored the interrelationship between cyto-kines(CKs)and sleep disorders,and this paper reviews the correlation between CID and inflammatory factors in the context of domestic and international research on the subject.