Study On The Material Basis Of Baihu Decoction In The Treatment Of Qifen Syndrome Based On Metabonomics

OBJECTIVE Based on the metabonomics method of ultra-high performance liquid chromatography-mass spectrometry,the biomarkers and Antipyretic Mechanism of Baihu Decoction in treating Qifen-fever syndrome were preliminarily studied.Based on the correlation between fingerprint and antipyretic effect of Baihu Decoction,the antipyretic active ingredients of Baihu Decoction were explored.METHOD Study on the antipyretic activity and potential biomarker of Baihu Decoction: lipopolysaccharide was used to establish an animal model of qifen fever syndrome,and Baihu Decoction was given one hour later,the temperature changes of experimental animals were recorded.The plasma metabolites were detected by UHPLC-MS.The qualitative and metabolic pathway analysis of differential metabolites were carried out by multidimensional statistical analysis,principal component analysis,partial least squares discriminant analysis(PLS-DA),orthogonal partial least squares discriminant analysis(OPLS-DA)and single-dimensional statistical analysis.Pharmacodynamics and plasma biomarkers of different batches of Baihu Decoction in treating Qi-fever syndrome: medicinal materials from different places were collected and decocted into different baihu decoction according to the orthogonal design method for antipyretic effect experiment,and the plasma samples were analyzed by UHPLC-MS,and the changes of potential biomarkers were studied.The antipyretic active ingredients of Baihu Decoction were determined by UHPLC-MS and grey correlation analysis method:UHPLC-MS method was used to study the fingerprint patterns of baihu decoction in 16 groups from different origins.The correlation between the fingerprints and the effects was studied by grey correlation analysis method,and the contribution of each component peak was determined.RESULTS The plasma metabolomics study of baihu decoction identified 18 kinds of potential biomarkers for its antipyretic effect.After LPS injection,endogenous metabolites changed,among which 7 species were up-regulated included Choline,Deoxycytidine,cytidine,cytosine,Oxindole,p-Cresol,Indoxyl sulfate,And 11 species were down-regulated included D-Proline,L-Citrulline,1-Palmitoyllysophosphatidycholine,1,2-dioleoyl-snglycero-3-phosphatidyl Choline,1-Oleoyl-sn-glycero-3-phosphocholine,Cholesteryl sulfate,Cyclohexyl sulfamate,embelin,L-Glutamine,which could be restored to normal in baihu decoction group.Through the plasma metabolomics study of 16 groups of baihu decoction,the biomarker related to the antipyretic effect of baihu decoction is cyclohexyl sulfamate.The grey correlation analysis determined that 26 components in baihu soup all had influence on the antipyretic effect,among which 12 components had significant influence(correlation degree γ0,i ≥ 0.9)and 14 components had relatively influence(0.8≤ γ0,i < 0.9).Through comparison with the control substance and literature records,it was determined that mangiferin had the greatest influence.CONCLUSIONS Baihu decoction can regulate the potential biomarkers with abnormal changes in the model of qifen fever syndrome to become normal and play an antipyretic role by regulating lipid metabolism,amino acid metabolism,pyrimidine metabolism and other pathways.Mangiferin has the greatest influence on its antipyretic effect.