| RATIONALES:Radix Bupleuri (Chaihu in chinese), with the main effects of cooling fever, soothing the depressed liver and improving the internal organs, has been used to compose many classical traditional chinese medicinal prescriptions, such as Xiao Chai Hu Tang, Da Chai Hu Tang, Xiao Yao San, Chai Hu Su Gan San, Chai Ge Jie Ji Tang and Zheng Chai Hu Yin. These prescriptions were widely used in internal medicine, gynaecology pediatrics and ENT dept. Studies have shown that the antipyretic effect of B. scorzoneri folium Willd was better than B. chinense DC., while B. chinense DC. was better than the B. scorzoneri folium Willd in the treatment of liver disease. It was confirmed that the two Radix Bupleuris were significantly different from the pharmacological effects of single herbs to chemical composition, genetic diversity and other aspects. However,(1) Chinese medicine is characterized in the form of prescriptions, there are different efficacy between prescriptions composed of different Bupleurum?(2) B. chinense DC. was cheap, so clinical application of the two Radix Bupleuris were always not to be distinguished. Prescription-based source of Bupleurum compatibility in the overall effectiveness of whether there are differences, not very clear. To this end, the elucidation of the difference in effect mechanism between B. scorzoneri folium Willd and B. chinense DC, is necessary to improve the accuracy of the medication and its efficacy. Metabolomics, as another "omics" following the genomics, proteomics techniques, has systemic and comprehensive advantages same as the comprehensive, holistic view of Chinese medicine about syndrome. These advantages can provide a new idea for pathogenesis of difficult diseases and mechanism of compounds of complex components. Therefore, this study selected two classic compounds, Xiao Chai Hu Tang and Chai Ge Jie Ji Tang in which Radix Bupleuri were the main medicine, to compare the effects of two different Radix Bupleuri from the angle of clinical application with metabolomics technology. In addition, it could provide technology platform for evaluating the efficacy of Chinese medicine.OBJECTIVE:To expore difference of two different Radix Bupleuri in the Chai-ge-jie-ji-tang and Xiao-chai-hu-tang on antipyretic effect and hepatoprotective effect from traditional indicators and potential biomarkers of body fluids and tissues. To find the difference of the potential biomarkers result in two kinds of radix bupleuri on antipyretic and hepatoprotective effect. To initially explore the mechanisms of effects of drugs in metabolite levels.METHODS:Groping dry yeast fever model, explore the difference of two different Radix Bupleuri singlely, or composed to Chai-ge-jie-ji-tang and Xiao-chai-hu-tang on antipyretic effect, and use the GC-MS metabolomics to compare the difference of two different Radix Bupleuri on the antipyretic effect in blood metabolite levels; groping acute liver injury model induced by carbon tetrachloride (CCl4), evaluate the difference of Xiao-chai-hu-tang with two different Radix Bupleuri on the hepatoprotective effect from biochemical markers (ALT and AST levels in serum) to serum and liver metabolite levels.RESULTS:(1) From the view of reducing the body temperature, B. scorzoneri folium Willd whether single herb or compound antipyretic effect was better than B. chinense DC; from the view of blood metabolomics, obvious disorders happened in blood metabolites of fever rats, the two Radix Bupleuri both has regulated the blood metabolites and the the regulatory role of B. scorzoneri folium Willd is slightly better than the B. chinense DC;(2) B. chinense DC has not shown very well antipyretic effect from the temperature results, but from the regulation of metabolic profiling analysis and antipyretic markers point of view, B. chinense DC also have a good regulation in the blood metabolites, indicating metabolites indicators has mores sensitive than traditional efficacy evaluation indicators;(3) Xiao-chai-hu-tang composed of the two different Radix Bupleuri respectively has shown no significant cooling the fever rats induced by dry yeast effect maybe due to the antipyretic mechanism of Xiao-chai-hu-tang inconsistent with the fever model induced by dry yeast;(4) Xiao-chai-hu-tang composed of the two different Radix Bupleuri respectively can reduce the levels of serum aminotransferase in acute liver injury induced by CC14in rat and have markedly hepatoprotective effect from the traditional biochemical markers, but there was no significant difference between both; from the blood and liver metabolomics perspective, the CC14has made rats happen obvious disorder in the energy metabolism, sugar metabolism and lipid metabolism; and Xiao-chai-hu-tang and bifendate can significantly regulate the levels of HDL in serum of liver injury rats, indicating that Xiao-chai-hu-tang and bifendate can improve the body lipid metabolism; Xiao-chai-hu-tang composed of B. scorzoneri folium Willd and B. chinense DC both can markedly regulate the levels of pyruvate in liver of injury rats, indicating that Xiao-chai-hu-tang can improve the body energy metabolism; Xiao-chai-hu-tang and bifendate both can significantly regulate the levels of choline and phosphorylcholine in serum and liver of injury rats, indicating that Xiao-chai-hu-tang and bifendate can protect the liver cell membrane, so as to reduce the levels of ALT, AST in blood.CONCLUSION:(1) on the antipyretic effect, B. scorzoneri folium Willd is better than B. chinense DC;(2) on the hepatoprotective effect, there is no significant difference between both;(3) metabolomics technology are effective means to evaluate the effect of traditional Chinese medicine from different sources and can explain the mechanism of drug action from a new perspective. |
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