| Objective:This study aims to establish the composition,network pharmacology of the target and disease,and to preliminarily predict the pharmacological effect of pauma pauma root,a natural herbal medicine of which there is little information.At the same time,analysis of the metabonomic and pharmacological experiments of rat blood was conducted,and the basis of the metabonomic analysis experiment of rats was established to explore the core effect and mechanism of action of this root muira pauma root from Brazil.,according to the result of prediction of network pharmacology and metabonomics,common analysis further determine Brazil muira pauma was possible pharmacological effects,and finally,through a pharmacological experiment Brazilian muira pauma was fatigue experiment,and establish a screening its effectiveness experiment mode,and validation to confirm its pharmacological action of the feasibility of network pharmacology,and metabolomics ideas,late muira pauma was late for the further study of the research and development of medicinal value to provide experimental basis for theoretical basis.Methods:Establish a network pharmacology of pauma pauma root of Brazil to evaluate the pharmacological effect:50 components of pauma root,based on the rainforest database(http://www.rain-tree.com/muirapuama.htm#.W67_VfZKI2w)and literature retrieval,obtain the CAS number and name,and use sciencefinder database to retrieve the structure of 50 compounds,and use ACD/Lab PerceptaSoftware operations will be to import the above composition structure,the export as a result,choose according to the results of compound using Swisstarget database(http://www.swisstargetpredictio.ch/),on the basis of molecular SMILES to find the appropriate targets,to download it to CSV format and organize related data to Probability>0.5 as the filter condition,will meet the conditions of the target and its corresponding ingredients to retain GeneMANIA through interaction between gene prediction website(http://genemania.org/)import some targets information,to build a PPI network established on PPI network,using cytoscape McOde cluster analysis module of software core subnet inference and building,using the target to analyze the enrichment of disease in the subnet,according to the result of enrichment of targets and predict related disease2.The application of super-high performance liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)combined with multivariate data analysis to explore the effect of endogenous metabolites in plasma of normal rats from Brazil,and the metabolic mechanism of muira Pauma root was studiedLow-dose intervention in normal SD rats,serum samples,using UHPLC-Q-TOF-MS technique to the control group and Brazil muira pauma was drug metabolism of rat serum samples contour analysis,combined with partial least squares analysis(PLS-DA)and orthogonal partial least-squares discriminant analysis(OPLS-DA),multivariate statistical analysis methods such as analysis on the impact of Brazil muira pauma was on normal rats metabolic marker and identify with the analysis of MetPA herbs to endogenous metabolic markers of the metabolic pathway of rats,this Brazilian muira pauma was the biological mechanism of effects on the body3.The Brazilian muira pauma was alcohol extract on acute toxicity experiment,the Brazilian muira pauma was toxic pharmacological research:a study of the toxicity of 281.84g/kg given to a rat,the loss of body mass,weight,and death of a rat within 1 hour,24 hours and 7 days.Muira Pauma-This dose-is of no toxicity to mice and mice given by gavage,and a preliminary conclusion is that the Brazilian dose of muira pauma is of minimal toxicity.;The drug is administered within this dose range.In mice as a condition for the construction of fatigue in mice model(adaptive weight loading swimming),the experiment is divided into high dose group(14 g/kg)content,middle dose group(7 g/kg)content,low dose group(3.5 g/kg)content in three groups,continuous lavage for five days later,the mice in the constant temperature water for three days of weight loading swimming experiment,its load conditions for the 8%of body weight in mice,the mice fell into the water immediately began to timing,mice to sink in water,and cannot be independent buoyancy for 10 seconds,the time can be identified as exhaustion time in mice.,and in nine days,the dosage of weight loading swimming 1 h after an pick eyeball blood in mice,at the same time take the liver and muscles under test,by pressing the kit manual operation steps to determine the content of hepatic glycogen in liver homogenate in mice,and muscle glycogen content in skeletal muscle homogenate,and serum lactic acid,serum urea nitrogen content and activity of lactic dehydrogenase.Results:1.The analysis of its pharmacological action network pharmacology prediction results showed that through the establishment of the Brazilian muira pauma was network pharmacology to forecast its pharmacological effects:based on the retrieval methods such as Brazil muira pauma was composition 59 species,according to the structure of the compounds,use ACD/Lab Percepta software operations will be to import the above composition structure,the export as a result,choose according to the results of compound using Swisstarget database,on the basis of molecular SMILES to find the appropriate targets,the main targets of Tyrosyl-DNACutive-phodiesterase 1 Muscleblind-like protein 3 Muscleblind-like protein 1 5-anhydro-d-Fructose reductase and other 67 corresponding targets were used to infer and construct the core subnet through the ESTABLISHED PPI network and the McOde cluster analysis module in the Cytoscape software,and the targets in the subnet were used for disease enrichment analysis to obtain Digestive systemSystem Diseases Neoplasms Neoplasms by Site Skin and Connective Tissue Diseases Diseases,Signs and Symptoms,etc2.Serum metabolomics muira pauma was ethanol extracts of rat serum metabolic analysis:Brazil muira pauma was serum metabolomics stability analysis results show that in the high dosage of medicine is endogenous metabolism of normal rats which have influence on the stability of low dose is relatively high dose difference bigger sample peak out of liquid phase and mass spectrometry conditions suitable for analysis of the experimental sample to QC sample repeatability characterize the stability of the samples and equipment,through the QC samples of different quality control during the period of coincidence detection has no obvious change,ion flow diagram of sample during the test,the sample and instrument has a good stability,after the completion of metabolites retrieval in metabolic pathway analysis,find the betaAlanine metabolism Propionate Metabolism Valine leucine and isoleucine degradation of arachidonic acid metabolism Citric acid cycle and other 30 significant metabolic pathways3.An acute toxicity study of an extract of pauma pauma root-this is a study from Brazil.The results confirm that the maximum tolerable dose of an oral dose of 281.84g/kg of raw medicine-pauma pauma root-this root pauma root is non-toxic.To construct an anti-fatigue model of weight-bearing swimming of a mouse,the results showed that the extract of pauma pauma root had a longer and significant difference in the duration of a weight-bearing swim compared to a control group given normal saline(P<0.05),in which the middle dose group and the low dose group can significantly reduce the lactate content and increase the activity of lactate dehydrogenase after the exercise of isoleucine mice,and the serum urea nitrogen content of the middle dose group is also significantly reduced(P<0.05)Compared to the control group,a medium dose of the extract,pauma pauma root,from Brazil,significantly increased the duration of swimming(P<0.01),the lactic acid content was significantly reduced(P<0.05)Lactate dehydrogenase activity increased(P<0.01),there was no significant difference between liver glycogen and muscle glycogen,and serum urea nitrogen content in the medium dose group was significantly reduced(P<0.05)Conclusion:1.Through the analysis of its pharmacological action network pharmacology predicted results analysis:the Brazilian muira pauma was the main component of the targets are mainly male/estrogen receptor muscle protein lipoprotein receptor activation peptide fragment 1 aldehyde ketone reductase family members B10 according to target presumed likely role in energy metabolism,sexual function,its effect on the fat storage,according to the analysis result forecast targets related diseases Brazil muira pauma was probably cirrhosis of the liver tumor in the digestive system diseasesThe therapeutic effect of respiratory diseases,etc.,network pharmacology analysis of the pharmacological effect of the pauma root of Brazil provides a theoretical basis for the development and discussion of the later study.Therefore,the following differential metabolite analysis can be carried out2.Based on metabolic marker variables significantly and preliminary screening of metabolic changes in intensity mark variable 49 on qualitative analysis of different metabolites of metabolic pathway enrichment analysis article 30 meaningful metabolic pathways,which mainly can be divided into four kinds of metabolic pathways,which are directly or indirectly involved in energy metabolism,Brazil muira pauma was in rats serum level can affect the body's energy metabolism hormone synthesis of amino acid metabolism,etc.Has a certain degree of correlationThe analysis of serum metabolomics that Pauma pauma root participates in a variety of metabolic pathways in a rat,which can reflect the internal process of its involvement,thus providing theoretical basis for further research and scientific basis for the development and utilization of new resources of traditional Chinese medicine.3.The toxicity study of This root muira pauma root,Brazil,proves that the safety of the safety of this root pauma root provides a dose scope for later administration and provides a theoretical safety benefit to the development of its medicinal value.After exhaustion exercise mice,the increase of energy depletion and metabolites of materials:ATP reserves decline,liver glycogen and muscle sugar original significant consumption,even will cause the loss of blood sugar level,further central fatigue caused by metabolic product during lactic acid accumulation and lactate dehydrogenase levels increase,the urea nitrogen content increased,therefore,as the basis of distinguishing fatigue effect anti-fatigue function experimental results prove that its muira pauma was alcohol alcohol extract in certain dose range has the anti-fatigue function,which is consistent with the prediction of network pharmacology,and metabolomics. |
PDF Full Text Request