Study On The Sleep-promoting/Anti-depression Effect Substances And Mechanism Of Action Of Schisandra Chinensis

Schisandra is a magnolia plant derived from the shennong herbaceous scriptures.It contains lignan,volatile oil and organic acids,of which lignan is one of the main active ingredients in Schisandra,and is also a key therapeutic component for its sedative-hypnotic and antidepressant effects.However,there have been some studies showing that schisandra lignans have sleep-promoting and antidepressant activities.However,these studies have mainly focused on a few common lignans and there is a lack of systematic studies on such components due to the large number and composition of lignans.Therefore,the material basis of the sleep-promoting and antidepressant properties of schisandra lignans is not fully understood.Accordingly,this paper develops the following studies.1.Pharmacodynamic studies on the sleep-promoting and antidepressant aspects of raw and liquor Schisandra chinensis.raw and liquor schisandra significantly increased the total distance of activity,the number of uprightness,and the ratio of time spent in REM and REM through behavioral studies,and WSC was superior to raw SC.RT-PCR,immunofluorescence,UPLC-Q-TOF-MS The results showed that raw and liquor Schisandra significantly reduced the relative expression levels of Bmal1 and Clock m RNA and increased the relative expression levels of Per2 m RNA.It reduced the expression of inflammatory factors,decreased NE,DA,CORT levels and increased 5-HT levels.It is suggested that raw,wine Schisandra has some therapeutic effect on insomnia mice,and the mechanism may be related to its regulation of biological indicators related to the neuro-endocrine-immune system in insomnia mice.This experiment investigated the effects of Schisandra chinensis on depressed mice.This experiment investigated the behavioral effects of Schisandra chinensis on mice in a depression model by means of sugar-water preference,open-field experiments and forced swimming experiments,and measured the monoamine neurotransmitters in mice.The results showed that liquor schisandra significantly increased the rate of sugar-water preference and the number of central crossing.Decreased resting immobility time.Increased 5-HT,DA content.The above results demonstrate that Drosophila wine has significant antidepressant effects,and its mechanism of action may be through the regulation of monoamine neurotransmitter levels in the mouse brain.2.Screening of the effective active ingredients of Schisandra chinensis in monosomal sleep promotion based on the model organism Drosophila.According to the quantitative analysis of lignans before and after concoction of Schisandra chinensis by our group in the early stage,it was found that there were differences in the content of lignans in raw and wine Schisandra chinensis.In this experiment,we mainly selected Schisandra chinensis A,B,C,alcohol A,alcohol B,ester A,ester B,ester E;gomisin G,gomisin J,gomisin D,angelicaoyl gomisin O,angelicaoyl gomisin Q,benzoyl gomisin O,crotonyl gomisin P,crotonyl gomisin H.Using the model organism Drosophila melanogaster as the research object,we conducted a pharmacological-pharmacodynamic screening of the above monomers of Schisandra chinensis for sleep promotion and The sleep duration,circadian activity rhythm and neurotransmitters of Drosophila were used as indicators.The results showed that:Schisandra chinensis alcohol B,Schisandra chinensis etherealin,Schisandra chinensis alcohol A,Gomisin G and Angelica chinensis acyl gomisin O exhibited significant anti-insomnia activity.On the basis of the above,a conformational study of the sleep-promoting effect of Schisandra chinensis monomer was conducted,and the analysis concluded that there was one hypomethylenedioxy group in the parent nucleus of the benzene ring,and it was between R1and R2,which was presumed to be the main group exerting the sleep-promoting effect;in addition,it was found that if two hypomethylenedioxy groups（Schisandra chinensis propylenes）were present at the same time,the monomer would not have a sleep-promoting effect instead3.Sleep-promoting study of SC based on npmd techniques.Using 16 monomers from Schisandra chinensis as active ingredients,the targets and pathways of Schisandra chinensis monomers in the treatment of insomnia were predicted.101 potential targets related to the treatment of insomnia by Schisandra chinensis monomers were obtained,and 7 core targets and20 signaling pathways with significant effects were predicted.The results provide an experimental basis for elucidating the mechanism of action of Schisandra chinensis monomer in the prevention and treatment of insomnia.The results showed that the antidepressant effects of G.schisandrae were obvious by behavioural and neurotransmitter content changes,including G.schisandrae methanin,alcohol A,and angelicae gomisin Q.The antidepressant effects were moderate by G.schisandrae b,ester E,and crotonyl gomisin H.The antidepressant effects were weaker by gomisin J,crotonyl gomisin O The weaker antidepressants were gomisin J,crotonyl gomisin O,and angelica yl-gomisin O.In addition,the antidepressant conformation of Schisandra chinensis monomers was further discussed,and it was found that the structures of Schisandra chinensis methyl,ethyl,alcohol methyl,ester e,angelica yl-gomisin Q and crotonyl-gomisin H all contained 5 or 6methoxy groups on the biphenyl ring,presumably because of the antidepressant effect of methoxy.However,it is strange that gomisin contains 4 methoxy groups,but also has antidepressant effect.5.Antidepressant study of SC based on network pharmacology and molecular docking techniques.Through screening,254 potential targets related to the antidepressant effect of Schisandra chinensis monomer were obtained,and then 14 core targets and 20 signalling pathways with significant effects were predicted.This laid the foundation for studying the molecular mechanism of schisandra monomer for the treatment of insomnia.6 Mechanistic studies on the sleep-improving effects of Schisandra chinensis monomer.The results of the network pharmacology and molecular docking tests were combined to select Schisandra chinensis alcohol B and Gomisin G as the monomers for the study of the mechanism,and it was found that Gomisin G and Schisandra chinensis alcohol B could increase the content of 5-HT and GABA and decrease the content of DA by using the neurotransmitters 5-HT,DA and GABA as indicators.It can be suggested that the effect of Gomisin G and Schisandrol B on sleep improvement is related to their levels of 5-HT,DA and GABA.Meanwhile,the study of wild-type Drosophila and inc-deficient Drosophila showed that gomisin G and pentosidine B could significantly up-regulate the expression of Per1 protein,a sleep rhythm gene.It can be suggested that the effect of gomisin G and pentosidine B on sleep improvement is related to their rhythm gene Per1.Finally,the results of experiments using RT-PCR on wild-type Drosophila,AKT1,and m TOR knockout Drosophila revealed that gomisin G and pentosol B both reduced the relative gene expression of AKT1 and m TOR.In both m TOR^-/-Drosophila,the relative expression of AKT1 was decreased in both GG and ST groups,suggesting that gomisin G and pentosidine B can regulate the AKT1-m TOR signaling pathway for sleep improvement,but mainly through the target of AKT1.In conclusion,this project firstly investigated the sleep-promoting and antidepressant effects of WSC and SC,and combined with the group’s previous basic research,16 Schisandra chinensis monomers were used as active ingredients,and then,based on Drosophila in vivo insomnia and depression model experiments and network pharmacology and molecular docking studies on Schisandra chinensis potent substances were carried out.Finally,the mechanism of insomnia was investigated.