| With the change of eating habits and living habits,the incidence and prevalence of Nonalcoholic fatty liver disease(NAFLD)increase year by year,which brings great pain and economic burden to patients.The pathogenesis of NAFLD has not been fully elucidated,and there are no effective therapeutic drugs.In 2019,the Commission of Health announced that Astragalus membranaceus was a medicinal material for both medicine and food.The active ingredients of Astragalus membranaceus include Astragalus polysaccharide,saponins,isoflavones,etc.The active ingredients of Astragalus membranaceus have various biological activities such as alleviating insulin resistance,regulating glucose and lipid metabolism,inhibiting inflammatory response,etc.,so as to play a protective role against NAFLD liver injury.However,the mechanism of effective active ingredients of Astragalus against NAFLD is still unclear.Therefore,in this paper,based on the overall research idea of network pharmacology,molecular docking and metabolomics,the possible mechanism of Astragalus membranaceus active ingredient’s intervention in liver injury of NAFLD mice was systematically elaborated from multiple levels and perspectives.Finally,combined with the practical application,developed a astragalus liver protection drink.The main conclusions of this paper are as follows:1.Network pharmacological methods were used to predict the active constituents,potential targets and molecular mechanisms of Astragalus compounds.Construct a compose-target-pathway interaction network between Astragalus compounds and NAFLD,including evaluation of drug similarity,prediction of oral bioavailability,construction of protein-protein interaction(PPI)network,and analysis of gene ontology(GO)terminology and pathway annotation.Finally,five key targets and 15 major signaling pathways related to the regulation of NAFLD by five active components of Astragalus compounds were determined.GO bioenrichment analysis results showed that the intervention of Astragalus compounds in NAFLD mainly involved the regulation of REDOX reaction,insulin regulation,inflammatory response and adipose cell decomposition.Molecular docking simulation method was used to further elucidate the active sites and binding degree of the ligands.The results of molecular docking showed that the astragalus compounds kaverol,genistein and daidzein could all bind to NAFLD targets INS,PPARG and AKT1,and all had good binding effect,and all had potential control effect on NAFLD.2.Non-alcoholic fatty liver induced by high fat and high sugar was taken as the model,and two kinds of astragalus isoflavones(Genistein,GEN)and(Daidzein,DAI)were used for intervention.The results showed that the two kinds of astragalus isoflavones significantly decreased the body weight,serum TG,TC,activity of liver function factors AST and ALT,liver inflammation level and serum LPS level in mice.These results indicated that both kinds of astragalus isoflavones could improve liver lipid metabolism disorder and inflammatory response caused by high fat and high sugar diet,and both had protective effects on liver injury in NAFLD mice.HPLC-QTOF/MS technique was used to study the mechanism of action of GEN and DAI against NAFLD.A total of 71 metabolites with significant differences in liver were screened and identified in the liver of mice in the four groups.The metabolic pathways involved mainly included phospholipid metabolism,arachidonic acid metabolism,tricarboxylic acid cycle,etc.The intrinsic mechanism of anti-NAFLD of two kinds of astragalus isoflavones was preliminarily clarified,which laid a foundation for subsequent studies.3.The optimal process ratio of Astragalus liver protection drink was obtained through response surface optimization experiment.The addition amount of Astragalus base solution was 13.10%,sugar was 5.90%,citric acid was 0.05%,xanthan gum was0.14%,taurine was 0.03% and vitamin C 0.02%.The shelf life of the beverage was predicted by constant temperature acceleration experiment.The shelf life of the beverage was up to 12 months,and the sensory,physical and chemical and microbial indexes of the beverage were within the range of national standards.Get a natural color,clear and transparent,pure taste,functional ingredients stable liver health drink. |
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