Preliminary Identification Of The Chemical Components And The Pharmacokinetic Study Of Mongonlian Medicine San-Chen-Pill

Mongolian medicine San-Chen-pill?SCP?was a traditional for pediatric prescription,it was composed of Calculus bovis,Carthamus tinctorius L.and Concretio silicea bambusae in the same amount according to 1:1:1.Calculus bovis belongs to precious,rare medicinal herb,it contained in the main efficacy components for bile acids composition,it can stimulate bile secretion,promote the lipid emulsion and the absorption of pharmacological effects.CA and HDCA belong to tetracyclic triterpenoid containing one unit of carboxylic acid,CA has been listed in Chinese pharmacopoeia2015 version.Carthamus tinctorius L.has coronary heart disease,angina pectoris and blood stasis syndrome effects,HSYA as the main chemical ingredient of Honghua,has been listed in Chinese pharmacopoeia?2015 version?.Concretio silicea bambusae,as a characteristic Mongolian medicine,played a very important role in Mongolian medicine,it was used for the treatment of convulsions,seizures and fever for young children.So far,there is no systematic study on the chemical components and pharmacokinetics of SCP,so the specific chemical components and mechanism of action of it are not clear.SCP has the curative effect of treatment of pulmonary disease,therefore,we choose non-small cell lung cancer cells?A549 cells?efficacy components of the active detection.We used the HPLC-MS/MS to establish a quantitative analysis at the same time a variety of compounds in rat plasma,it is applied to rats in vivo medicine dynamics research.In order to provide a scientific basis for the development and utilization of SCP,this study clarified the medicinal substances of SCP from two aspects:serum pharmacokinetics and pharmacokinetics.The first part of the study was the separation of the chemical components in SCP by using a high resolution mass spectrometer with a quadrupole in series and a High-performance liquid chromatography electrostatic field orbital well,the first-order Molecular Ion peak and the second-order fragment ion information were obtained by the first-order full scan and multi-order fragment scan in the positive-negative ion mode of high-resolution Q-Exactive detector.By comparied the retention time,first-order Mass Spectrometry and second-order fragment ion of the reference material with those reported in the literature,the compounds were preliminarily identified.Forty-six active components in SCP were identified,including 38 in Honghua and 8 in Niuhuang,and to provide a basis for the study and quality evaluation of SCP.The second part of this study was based on the studyed of the serum pharmacology of SCP by serum pharmacokinetics-serum pharmacology,and we have studyed the blood components of SCP,the results showed that not all medicinal ingredients can be into the blood,but it may also be related to the conversion and metabolism of medicine in the body.In the previous serum-pharmacochemical experiment of SCP,the study pointed out that the components into the blood were CA,HDCA,HSYA,SRG,KFR and AHSYB active components^[1],and these active components were all reported to have clear pharmacological effects.By combination of serum pharmacochemistry-serum pharmacological studyed six kinds of components in the plasma,we would finded out components of plasma that has pharmacological effects on A549 cells.The six components in five different time point in the plasma were quantitative analysis,and the serum pharmacological experiments were carried out in vitro,the results showed that the serum has the inhibiting A549 cell proliferation and apoptosis in A549 cells of effects,and has the concentration-response relationship.Based on the spectral relationship,the order of the correlation coefficient with the survival activity of A549 cells was as follows:HSYA>HDCA>AHSYB>SRG>KFR>CA;then the order of correlation coefficient with ROS content in A549 cells was as follows:HSYA>HDCA>SRG>AHSYB>KFR>CA.The third part of this study was the pharmacokinetic study of 6 act ive ingredients in SCP.The results showed that the C_max of CA and HDCA were 3.33h and 3.53 h,t1/2 was 4.05±2.82 h and3.85±1.69 h,and T_max was 3.33±4.44 h and 3.53±4.33 h,respectively.The pharmacokinetic parameters of these two components had little difference.The C_max of HDSYA was 1,400.48±1,57.10?g/L and AUC_0-t was 4,925.16±1,078.07 kg/L*h,which were the components with the highest peak concentration and the highest bioavailability.For KFR,AHSYB and SRG,the rank orders of AUC_0-t and C_max were both KFR>AHSYB>SRG,identical to the order of their contents in SCP.We elucidated the pharmacokinetic characteristics of the six active components,and the bioavailability of these components increased to varying degrees in vivo.To sum up,based on the identification of the active components in SCP and the study of pharmacokinetics,the identification of the active components in SCP by HPLC-MS/MS was carried out,the possible pharmacodynamic substances of SCP were elucidated from two aspects of"serum pharmacology-pharmacokinetics",and the pharmacodynamic substances with inhibitory effect on A549 cells in SCP and their absorption and metabolism in vivo were obtained,in order to provide scientific basis for the development and utilization of SCP.