Screening The Best Compatibility And Investigation On The Spectrum-effect Relationships Of Active Fractions From Xiaoyaosan

Ethnopharmacology:Depression is a common mental disease, it is predicted that in2020it will be the world’s second largest burden of disease source, and the harm has drawn the medical and health community’s attention. The Xiaoyaosan is one of the most common ways to treat depression, clinical and experimental studies have shown that it indeed has the antidepressant effect, currently, it has been a hot spot on the research of Xiaoyaosan in traditional Chinese medicines, but the anti-depression efficacy of Xiaoyaosan has not been reported in the literature. The antidepressant pharmacodynamic material basis of Xiaoyaosan means the chemical composition that has the antidepressant effect in the compound, therefore clarifying the basis of efficacy substances, not only reveal the integrity of its antidepressant effectiveness of multi-component multi-target effects complexity and scientific compatibility, but also provide a scientific basis for the party, as well as lay the foundation for better antidepressant efficacy of new drugs from traditional Chinese medicine research and development and a reference basic for other Chinese herbal compound effective substances. Chinese medicine spectrum activity relationship is a new idea of Pharmacodynamic Constituents of TCM research, its purpose is to reveal the relationship between the chemical composition and the efficacy of traditional Chinese medicine contains the spectrum efficiency, in order to clarify and efficacy of the chemical substances basis. Our group has done a lot of work to Xiaoyaosan, we have been screened out effective parts from the compound and the best compatibility proportion of the antidepressant effect of Xiaoyaosan from mice despair model (mouse forced swimming test and mouse tail suspension test), found the closely related to the chemical composition. However, the experimental results obtained by a single mouse model of despair need to be a verification of progress, the study based on CUMS rat model of behavior and metabolomics on the antidepressant Xiaoyaosan active ingredientsmore in depth. Objective:Based on chronic mild and the unpredictable stress (CUMS) rat model of behavior and metabolomics technology certification preparatory mouse model of despair to find the Xiaoyaosan antidepressant active site best compatibility ratio and antidepressant activity closely related to the chemical composition, to further clarify the material basis of Xiaoyaosan efficacy of antidepressant effect.Material and methods:Xiaoyaosan antidepressant effective parts XY-A and XY-B used the way of two-factor (effective fractions XY-A and XY-B are two factors) three-level (0、1、3of the best dosage can be divided into three levels) design compatibility studies, with the component compatibility, pre-screened through a mouse model of the best compatibility group parts Xiaoyaosan the compound venlafaxine Fortunately (positive group) for drug intervention CUMS model combines comprehensive survey of singly housed model Xiaoyaosan antidepressant effective compatibility component parallel to the rats the number of cells, rearing, sucrose preference rate, body weight and plasma metabolites, determine the best ratio of compatibility and optimal dose. By GC-MS method to establish Xiaoyaosan antidepressant effective parts compatibility component fingerprints, using a variety of relational analysis (principal component analysis, correlation analysis, multiple regression analysis), establish the relationship between spectral efficiency, looking for the treatment of depression the characteristic peaks, and from the map to determine the qualitative identification of the chemical composition on the efficacy contribution.Results:1. Ehavior and metabolomics analysisThere are significant differences between the normal group and model group behavior, if it can separate obviously on the metabolic profiling, then we have the successful model. Combined with the corresponding load chart and independent samples t test, there are11potential confounding biomarkers. Based on the CUMS model behavior and plasma within the metabolomics,the results show that the normal group, model group, positive and effective parts of the Xiaoyaosan compatibility group play a different role in the intervention, which XY-A2B2(XY-A:XY-B=2:2) group, compared with the other groups, in terms of behavior can significantly improve the number of the CUMS rats parallel grid, rearing, rat body weight and sucrose preference ratio in the plasma metabolomics aspects of XY-A2B2group from the normal control group, the farthest away from the model group, indicating that its antidepressant effect better than the Xiaoyaosan compound groups and venlafaxine group. Therefore, this study screened out the best antidepressant effective parts compatibility group, that is, when the effective part in crude drug, XY-A and XY-B are all92.6g/kg, the antidepressant effect is the best.2. Spectrum efficiency results(1) Based on the relationship between spectral efficiency research ideas, the application of GC-MS chromatographic analysis the effective part due to the chemical composition in differences caused by the pharmacodynamic differences of Xiaoyaosan antidepressant compatibility component "spectrum". By examination of the various indicators, it shows that the analytical method established in this study is able to meet the technical requirements of fingerprint analysis; GC-MS fingerprints obtained can response the effective parts compatibility group copies of the main chemical components. At the same time, the characteristic peaks in the fingerprinting peak area determination.(2) Combined with the compatibility component spectrum analysis and pharmacodynamic relationship, with the application of correlation analysis, regression analysis and other related analysis, each other support, the establishment of spectral efficiency related to find and identify some related to the treatment of depression. And looks into the11active ingredients, which identified six (camphene, atractylone ligustilide, palmitic acid, atractylenolide I Atractylodes lactone II), and5unknown compounds5.The antidepressant activity of some chemical components has been confirmed by the literature, to some extent proved the objectivity and accuracy of analytical methods used in this study. Conclusion:1. Successful evaluation effective parts As Xiaoyaosan antidepressant compatibility component content of the chemical composition differences caused by the pharmacodynamic differences. The study found that the effective parts compatibility group formed parts better than the separate parts of the XY-A, XY-B, and filter out the best antidepressant compatibility of components, that is, when the effective part in crude drug, XY-A XY-B were92.6g/kg when the antidepressant effect is the best. This study is based on the effective parts compatibility spectrum activity relationship studies laid the foundation, at the same time, the results of this study provide some reference value for the research and development of new antidepressant component of traditional Chinese medicine.2. Based on the spectrum activity relationship of, with the application of GC-MS chromatographic analysis and a variety of relational analysis, the establishment of the spectrum-effect relationship successfully find11antidepressant active ingredient (camphene, atractylone, Ligusticum lactone,palmitic acid, atractylenolide Ⅰ, Atractylodes lactone Ⅱ), and provide a valuable reference for quality control and efficacy of Xiaoyaosan substance basic research.3. Integrated our group analysis showed that atractylone ligustilide, palmitic acid, atractylenolide Ⅰ atractylenolide Ⅱ identified for the antidepressant Xiaoyaosan active ingredients.4. The spectrum activity relationship based on effective parts compatibility research reflects the overall concept of the Chinese herbal medicines, and other material basis for study of the efficacy of Chinese herbal compound provides new ideas and methods.