Study On The Material Basis And Mechanism Of Action Of Bailemian Capsule In The Treatment Of Insomni

Insomnia is a common mental disease,which is closely related to cardiovascular diseases,heart diseases,various neurological diseases and mental diseases,and seriously affects people’s life health.As a new type of Chinese herbal medicine compound,Bailemian capsule is composed of 15 kinds of Chinese herbal medicines such as lily and rehmannia.It has the effect of clearing the heart and calming the mind,nourishing Yin and clearing heat,which is widely used in clinical practice to treat insomnia.A large number of modern clinical studies have shown that Bailemian Capsules can largely alleviate the symptoms of insomnia patients who cannot sleep at night,wake up easily and wake up early.This research group has already analyzed the in vitro composition of Bailemian capsule,but the substance basis for its in vivo effect is not clear,and its target and action pathway for the treatment of insomnia are not yet known,so this research aims to clarify the in vivo substance action basis and action mechanism of Bailemian capsule for the treatment of insomnia,in order to provide theoretical basis and relevant evidence for the further development and utilization of Bailemian capsule.The research content of this project is as follows:(1)The UPLC-QE-Orbitrap-MS technique was used to qualitatively analyze the entry components of Bailemian capsules in order to clarify their pharmacological basis.A total of 47 compounds were identified from the drug-containing serum,and 24 compounds were found to enter four brain regions,namely,hypothalamus,hippocampus,frontal cortex and temporal cortex,to exert drug effects.(2)Based on the network pharmacology study and molecular docking technology validation of 24 brain-entering ingredients,to further screen its main pharmacodynamic substances and preliminarily predict its pathways of action for the treatment of insomnia.Through the screening of key targets,protein interaction network analysis and pathway enrichment analysis,it was found that Bailemian capsules mainly act through schisandrin and isoleucine as active ingredients,MAPK1,GRIA1,GRIA2 and other 12 targets were used as key targets to exert their effects through glutamatergic synapses and serotonergic synapses.(3)The small molecule fluctuations caused by sleep deprivation were analyzed by means of serum metabolomics and hypothalamic metabolomics to clarify the effect and mechanism of action of Bailemian Capsules on its modulation.After serum metabolomics analysis,a total of 66 differential metabolites were obtained,among which 13 differential metabolites,including indole acetaldehyde,were significantly modulated,mainly through the metabolic pathways of alanine,aspartate and glutamate metabolism,glyoxylic acid and dicarboxylic acid metabolism to resist insomnia deprivation.The hypothalamic metabolomics analysis revealed that Bailemian Capsules significantly modulated 19 differential metabolites affected by sleep deprivation,with D-arginine and D-ornithine metabolism,nitrogen metabolism,D-glutamine and D-glutamate metabolism as metabolic pathways to exert therapeutic effects on insomnia.Combining the results of serum metabolomics and hypothalamus metabolomics,a total of 7 shared differential metabolites and 7 shared metabolic pathways were found.It is presumed that Bailemian Capsules can alleviate the symptoms of insomnia mainly through these 7 metabolites and metabolic pathways.(4)In order to further clarify the mechanism of action of Bailemian capsules,a preliminary exploration of the changes in intestinal flora homeostasis induced by sleep deprivation was performed by means of 16S rRNA.Twenty intestinal bacteria including norank_f_Muribaculaceae(p<0.05),Alloprevotella(p<0.05),and Rikenellaceae_RC9_gut_group(p<0.05)were found to be significantly changed after sleep deprivation.Norank_f_Muribaculaceae were regulated back to near-normal levels after highdose administration of Bailemian capsules,and defluviitaleaceae UCG-011 was also modulated to near-normal levels after low-dose administration of Bailemian capsules.In conclusion,this study initially clarified the pharmacological basis of Bailemian Capsules,and investigated the mechanism of action of Bailemian Capsules in the treatment of insomnia from multiple perspectives based on network pharmacology,metabolomics and 16S rRNA technology,providing a research basis and theoretical basis for the development and application of Bailemian Capsules,and providing a reference value for the study of the substance basis and mechanism of action of other Chinese herbal compounding.