Differences of antipyretic effect between Qingkailing soft capsule and hard capsule based on metabonomics

Abstract

The antipyretic effects of Qingkailing soft capsules and hard capsules were compared based on metabonomics technology,so as to provide basis for clinical rational use and quality control evaluation of its preparations. By using ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry( UPLC-LTQ/Orbitrap),and multivariate tatistical methods such as principal component analysis( PCA),partial least squares-discriminate analysis( PLS-DA) and orthogonal signal correction partial least square discriminant analysis( OPLS-DA),the changes of plasma endogenous metabolites in rat fever model induced by dry yeast were studied,so as to look for biomarkers related to fever. Based on these results,the antipyretic effects of two types of Qingkailing preparations were compared. The results indicated that metabolic profiles of the experimental groups could be distinguished distinctly,and 8 endogenous metabolites showed differences as compared with the normal control group( P<0. 05),including nicotinic acid,choline,hippuric acid,phosphocholine,Lyso PC( 14 ∶ 0),Lyso PC [16 ∶ 1( 9 Z) ],Lyso PC( 18 ∶ 0) and Lyso PC [20 ∶ 3( 5 Z,8 Z,11 Z) ]. They could be regarded as biomarkers related to fever. Qingkailing soft capsule and hard capsule had different effects on the regulation of plasma metabolites in yeast-induced fever model rats. Qingkailing soft capsule had different degrees of callbacks on eight biomarkers,including significant callbacks on nicotinic acid( P<0. 05),hippuric acid( P< 0. 01),phosphocholine( P< 0. 05),and Lyso PC [20 ∶3( 5 Z,8 Z,11 Z) ]( P<0. 05),while hard capsule only had significant callbacks on nicotinic acid( P<0. 05),hippuric acid( P<0. 01),and phosphocholine( P< 0. 05),with no callbacks on choline,Lyso PC( 14 ∶ 0),Lyso PC [16 ∶ 1( 9 Z) ],Lyso PC( 18 ∶0),and Lyso PC [20 ∶3( 5 Z,8 Z,11 Z) ]. This indicated that Qingkailing soft capsule had better callback effect than hard capsule. In this study,Qingkailing soft capsules and hard capsules were used to intervene the changes of related biomarkers in yeast-induced fever rat models,and then the antipyretic effect and mechanism between these two kinds of capsules were compared. The two dosage forms played an antipyretic role mainly by regulating lipid metabolism and controlling inflammation. The callback effect of soft capsule on the potential biomarkers of lysophosphatidylcholine was significantly higher than that of hard capsule. The differences in antipyretic effect of Qingkailing soft capsule and hard capsule were expounded from the point of metabonomics,providing experimental data and theoretical basis for the selection of clinical dosage forms.