The Mechanism Of Lignans In Schisandra Chinensis In The Treatment Of Alzheimer’s Disease And The Effect Of Polysaccharides On The Absorption And Metabolism Of Lignans

Schisandra is the dry ripe fruit of the Magnoliaceae Schisandra chinensis（Turcz.）Baill.Lignans are the main active components in Schisandra chinensis.Studies have shown that schisandra lignans can be clinically used to improve cognitive function and treat neurodegenerative diseases,but its mechanism of action has not been clear.In the early stage of our research group,we studied the blood components of Schisandra lignans and their effects on neurotransmitters in the plasma of Alzheimer’s disease（AD）rats,and analyzed them from the perspectives of plasma metabolomics and urine metabolomics.However,from the perspectives of pharmacokineticspharmacodynamics（PK-PD）and fecal metabolomics,lignans play a role in the treatment of Alzheimer’s disease.The mechanism of action in the treatment of AD is still unclear,and the effect of another important active component polysaccharides in Schisandra chinensis on the absorption and metabolism of lignans has not been explored.Therefore,in this paper,fecal metabolomics,in vitro intestinal bacterial metabolism,pharmacodynamics and pharmacokinetics have been studied.In several aspects,the material basis of Schisandra lignans in the treatment of Alzheimer’s disease and the effect of polysaccharides on the absorption and metabolism of lignans were studied,which provided a scientific basis for the study of the mechanism of Schisandra chinensis in the treatment of Alzheimer’s disease.The specific research contents are as follows:1.Study of fecal metabolomics in AD rats treated with Schisandra lignansThe rat AD model induced by Aβ25-35 was established,and the therapeutic effect of Schisandra lignans on AD rats was evaluated by Morris water maze test,biochemical test,pathological test,HE staining and immunohistochemical test.Based on UPLC-Q-TOF-MS and UPLC-TQ-MS technologies,the faecal samples were combined with non-targeted and targeted metabolomics to explore the regulatory effect of Schisandra lignans on AD model rats.Combined with multivariate statistical analysis,potential biomarkers with significant differences were screened and pathway analysis was performed.A total of 19 potential biomarkers related to AD disease were identified,involving metabolic pathways: bile acid metabolism,energy metabolism,linoleic acid metabolism,steroid metabolism,vitamin metabolism,and arachidonic acid metabolism.At the same time,the targeted quantification results of bile acids showed that Schisandra lignans could significantly reduce the contents of glycodeoxycholic acid（GDCA）,deoxycholic acid（DCA）and lithocholic acid（LCA）in the feces of AD rats.Cholic acid（CA）,glycocholic acid（GCA）,taurocholic acid（TCA）,ursodeoxycholic acid（UDCA）,tauroursodeoxycholic acid（TUDCA）and chenodeoxycholic acid（CDCA）content The results showed that schisandra lignans reduced neuroinflammation,oxidative stress and neurotoxicity by regulating multiple metabolic pathways in AD rats.2.Association analysis of pharmacokinetics and pharmacodynamics of Schisandra lignans in the treatment of Alzheimer’s diseaseUPLC-TQ-MS technology combined with microdialysis sampling technology was used to detect the active components of lignans and endogenous neurotransmitters related to curative effect in the hippocampus and plasma of rats treated with blank and AD model rats,to compare wood lignans.Pharmacokinetic differences of lipin in normal rats and AD rats,and using the neurotransmitter content as the pharmacodynamic index,the correlation analysis of pharmacokinetics and pharmacodynamics was used to evaluate the treatment of schisandra lignans in AD rats research on the material basis of pharmacodynamics.The pharmacokinetic results showed that the AD group had better absorption and slower elimination of Schisandra lignans than the normal group.The correlation analysis results of pharmacokinetics and pharmacodynamics showed that there was a complex relationship between the active components of lignans and neurotransmitters,not a simple linear relationship.Glutamate（Glu）,acetylcholine（Ach）,γ-aminobutyric acid（GABA）changed clockwise with the concentration of lignan active ingredients,5-hydroxytryptamine（5-HT）,aspartic acid（Asp）,glycine（Gly）and norepinephrine（NE）changed counterclockwise with the concentration of active lignans.The results showed that ASP and Glu showed a downward trend,and 5-HT,GABA,Gly and NE showed an upward trend with the change of lignan active ingredient concentration.The results of the study showed that the AD group had increased absorption of schisandra lignans,which could protect the function of the central nervous system by regulating the content of neurotransmitters in the brains of AD rats.3.The effect of Schisandra chinensis polysaccharide components on the intestinal bacteria metabolism of lignan componentsIn vitro intestinal bacterial metabolism models of blank rats and AD rats were established,and UPLC-Q-TOF-MS technology was used to analyze the components and metabolites of Schisandra lignans.In vitro effects on intestinal bacterial metabolism.It was found that the metabolic trends of lignans in the intestinal flora of mice were basically the same,showing a trend of first decreasing,then increasing,and then greatly decreasing.The metabolic rate of lignans in AD group was higher than that of blank group,and a total of 23 species were identified.metabolite.In the blank group,polysaccharides can slow down the metabolism of Schisandrin B,Schisandrin A,Schisandrin B,Gomisin K1,Gomisin G,Angelica acyl Gomisin Q,accelerate the metabolism of Gomisin E,Gomisin D,However,in AD group,polysaccharides could accelerate the metabolism of gomisin E,gomisin D,and benzoyl gomisin H,and the rest of the wood No significant effect was found for the liposome fraction under the influence of polysaccharides.The results show that schisandra lignans can be metabolized in the intestinal flora of mice,and schisandra polysaccharides can affect the metabolic rate of schisandra lignans in the intestinal flora,so schisandra polysaccharides may affect the intestinal lignan absorption of nutrients.4.Effects of Schisandra chinensis polysaccharide components on the pharmacokinetic behavior of lignan componentsUsing UPLC-TQ-MS technology,the pharmacokinetic process of the main components of Schisandra lignans entering blood in normal rats under the influence of Schisandra polysaccharide was compared and analyzed.The results showed that the polysaccharide promoted the normal rats to schisandrin B,schisandrin A,gomisin E,gomisin K1,schisandrin A,gomisin G,benzoyl gomisin H,gomisin D.Absorption,prolonging the duration of drug effects of gomisin E,gomisin K1,schisandrin A,and schisandrin B in rats,accelerating the absorption of schisandrin B,increasing schisandrin B,schisandrin B,schisandra Bioavailability of A,Gomisin E,Gomisin K1,Schisandrin A,Gomisin G,Benzoyl Gomisin H,Gomisin D.It shows that Schisandra chinensis polysaccharide may improve the efficacy of the drug by promoting the absorption of Schisandra lignans.In summary,this paper adopts a variety of modern technical means,firstly discusses the regulatory effect and pharmacodynamic mechanism of Schisandra lignans on metabolic pathways in AD model rats,and clarifies the efficacy basis of Schisandra lignans in AD rats.,and then further explored the effect of another active component polysaccharide in Schisandra chinensis on the absorption and metabolism of lignans from the in vitro and in vivo processes of lignans,which provided a scientific basis for further elucidating the mechanism of Schisandra chinensis in the treatment of AD.