| Research BackgroundPaeoniae Radix Alba(PRA)is a traditional Chinese medicine commonly used in traditional Chinese medicine,which is the preferred medicine for blood deficiency and liver depression.Pharmacology and clinical studies have shown that PRA has obvious blood,antidepressant,analgesia,neuroprotective and immunoregulation effects,which can be used for the treatment of depression,neurological and joint pain,and has a wide range of effects.Paeoniflorin(PF)and Albiflorin(AF)are the two kinds of single monoterpene compounds with the highest content in PRA,the results of previous studies showed that PF and AF also had certain enrich blood and antidepressant effects,and contrast research on Radix paeoniae Rubra showed that PF was an effective but not exclusive ingredient of PRA,and that the AF was the characteristic active ingredient of PRA,To a certain extent,the material basis of the effect of nourishing blood and smoothing the liver of PRA was clarified.At the same time,based on the basic theory of Traditional Chinese Medicine(TCM),the research group explored the model of the stagnation of liver qi and blood deficiency syndrome in accordance with the characteristics of TCM syndromes,and finally establishes a rat model by irradiation combined with chronic restraint stress,and based on the NEI network system,The pathological features of the syndrome were preliminarily clarified from the whole animal and cell level.Previous studies have laid a foundation for clarifying the nature of the stagnation of liver qi and blood deficiency syndrome and the mechanism,material basis of the effect of PRA on nourishing blood and smoothing the liver.However,TCM syndromes have the characteristics such as complexity,and Chinese medicine also has the characteristics of multiple components and multiple’ targets.Therefore,it is necessary to conduct comprehensive and in-depth research with modern technology.Metabonomics Technology is a method to study the changes of endogenous metabolites in organism,which can be analyzed from the whole point of view,which is consistent with the whole view of TCM and the characteristics of syndrome differentiation and treatment.Research PurposesBased on the above research background,this subject will be based on the results of NEI Network research,combined with the "syndrome-effect" correlation,through the metabolic group analysis of the model rats,improve the research on the essence of the syndrome,at the same time analyze the effects of PRA and its active ingredients,PF and AF on the metabolic markers of the stagnation of liver qi and blood deficiency syndrome,to elucidate the effect and material basis of PRA on nourishing blood and smoothing the liver.Research Methods and ContentsThe rat model of the stagnation of liver qi and blood deficiency syndrome was established by irradiation combined with chronic restraint stress and solitary culture.The efficacy of PRA and PF,AF on nourishing blood and smoothing the liver was evaluated by behavioral,physiological and biochemical indicators.On this basis,the use of LC-MS metabolomics technology combined with multivariate statistical analysis method to analyze the changes of small molecule metabolites in the rat model,explore the nature of syndromes,and based on the the model rat of biomarkers,the mechanism of the efficacy of PRA and its effective constituents PF and AF on nourishing blood and smoothing the liver was studied.The main research contents are as follows:1.Study the effect of PRA on nourishing blood and smoothing the liver based on the stagnation of liver qi and blood deficiency syndromeThe experimental rats were randomly divided into four groups,that is,the blank group(KB),model group(MX),PRA(BS),Xiaoyao pill Group(XYW),with irradiation combined with chronic restraint stress combined with solitary culture,the rat model ofthe stagnation of liver qi and blood deficiency syndrome was established,Taking Xiaoyao pill as a positive control drug,to observe the effect of PRA on the behavioral(Open box and Elevated cross maze),peripheral blood(WBC,RBC,HGB),HPA axis(ACTH,CRH,CORT)of the rat model,and to discuss the essence of the stagnation of liver qi and blood deficiency syndrome and the effect of PRA on the syndrome.2.Study on the effects of PF and AF based on the efficacy of "nourishing blood and smoothing liver"of PRATaking PRA as a positive control drug,to compare the effects of PF and AF on the behavioral and physical indexes of the rat model of the stagnation of liver qi and blood deficiency syndrome with PRA as a positive control drug,and to study the effect of PF and AF on the material basis of the effect of PRA on nourishing blood and smoothing liver.3.Metabolic profiling analysis of the stagnation of liver qi and blood deficiency syndrome rats and the mechanism of the effect of PRA on nourishing blood and smoothing the liverThe changes of metabolites in rat serum were selected by the combination of liquid-mass technique,principal component analysis and partial least squares discriminant analysis,and the possible biomarkers were screened out,MetaboAnalyst website was used to analyze the data,To observe the changes of serum metabolic spectrum in the stagnation of liver qi and blood deficiency syndrome rats and to determine the essence of the syndrome.To analyze the regulative effect of PRA on abnormal metabolites,and to explore the mechanism of the effect of PRA.4.Effects of PF and AF on serum metabolomics in rat model of stagnation of liver qi and blood deficiency syndromeThe serum samples were detected by liquid-mass joint technique,the progenesis was processed by peak recognition,matching and normalization,and the SIMCA,MetaboAnalyst software was used to analyze the data,and the potential biomarkers were screened in variable importance projection(VIP)>1 and T-test of P<0.05.To investigate the effects of PF and AF on the rat model of stagnation of liver qi and blood deficiency syndrome by detecting and analyzing the difference of serum metabolites in blank group,model group and drug delivery group.5.Effects of PF and AF on cerebral cortex metabolomics in rat model of stagnation of liver qi and blood deficiency syndromeThe changes of small molecular metabolites in cerebral cortex were observed by LC-MS technique combined with principal component analysis,SIMCA and Metaboanalyst software were used to select and identify the differential compounds and analyze the related metabolic pathways.To explore the mechanism of nourishing blood and smoothing the liver effect of PF and AFResearch ResultsThe pharmacological research results showed that the model rats with stagnation of liver qi and blood deficiency syndrome sugar consumption,open box and elevated cross maze behavioral activities are significantly reduced(P<0.05,0.01,0.001);the contents of peripheral blood(WBC,RBC,HGB),there were different degrees of reduction(P<0.05,0.01,0.001);the HPA axis content increased significantly(P<0.01.0.001).PRA,PF and AF have a certain degree of regulation in all above abnormal indexes.The results of Metabolomics study showed that the contents of small molecule metabolites such as phosphatidylcholine,lysophosphatidylcholine,and amino acids in rats with stagnation of liver qi and blood deficiency syndrome were changed.PRA and PF and AF can play the role of nourishing blood and smoothing the liver by regulating the related abnormal metabolic pathways.Research Conclusions1.PRA and its active ingredients PF and AF can play a role nourishing blood and smoothing the liver by regulating abnormal behaviors such as behavior,peripheral blood,and HPA axis;2.The stagnation of liver qi and blood deficiency syndrome rats are involved in metabolic pathway abnormalities such as glycerophospholipid metabolism,linoleic acid metabolism and amino acid metabolism in vivo.PRA and its active ingredients PF and AF can exert the effect through regulating abnormal metabolic pathways.This subject is based on the theory of "syndrome-effect",based on the research of NEI network and our patented technology,this paper probes into the syndrome essence of the stagnation of liver qi and blood deficiency syndrome in the perspective of the change of endogenous metabolites in systemic biology,and at the same time,based on the efficacy of PRA,"nourishing blood and smoothing the liver",the effective of PF and AF in the PRA was studied from the whole level,and further clarified the function and material basis of the effect of PRA on nourishing blood and smoothing the liver. |
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