| Qi-Shen-Ke-Li(QSKL)is a traditional Chinese medicine that has long been used for the routine treatment of coronary heart disease and chronic heart failure(CHF)in China.It is composed of six herbs: Salvia miltiorrhiza Bunge.,root(SMB),Astragalus propinquus Schischkin.,root(APS),Lonicera japonica Thunb.,flower(LJT),Scrophularia ningpoensis Hemsl.,root(SNH),Glycyrrhiza glabra L.,root(GGL)and Aconitum carmichaelii Debeaux.,lateral root(ACD).Pharmacological research shows that QSKL has the effect of treating CHF,but its compatibility mechanism and material basis are not clear.In this study,liquid chromatography-mass spectrometry was used to study the differences in pharmacokinetic characteristic of bioactive compounds in QSKL before and after compatibility.In addition,the pharmacokinetics and tissue distribution of bioactive compounds of QSKL in healthy and heart failure rats were systematically studied.The main research contents include the following aspects:1.Comparative analysis of the bioactive compounds of QSKL and single-herbs in healthy rats based on pharmacokineticsUsing liquid chromatography-mass spectrometry(LC-MS)to establish a chemical composition analysis method for QSKL and their single herbs,54 related chemical compounds were identified through relevant literature data and mass spectrometry analysis results.By comparing the chromatograms of QSKL and single herbs,the source of the chemical components in the formula was attributed.Based on this,an ultra-high performance liquid chromatography-triple quadrupole mass spectrometry method was developed for the analysis of 18 bioactive compounds(four SMB compounds,two APS compounds,one LJT compounds,one SNH compounds,seven GGL compounds and three ACD compounds)in healthy rat plasma.A comparative analysis of the pharmacokinetic characteristic of 18 components before and after the compatibility of QSKL in healthy rats.The results show that the formula promoted the absorption of salvianolic acid A,dihydrotanshinone I,acteoside,glycyrrhetinic acid,benzoylhypacoitine and benzoylmesaconine,reduced the absorption of tanshinone I,cryptotanshinone,formononetin,calycosin,chlorogenic acid,glycyrrhizic acid,liquiritigenin,isoliquiritigenin,liquiritin,isoliquiritin and benzoylaconine,prolonged the effect of dihydrotanshinone I,cryptotanshinone,chlorogenic acid,glycyrrhizic acid,isoliquiritigenin,liquiritin,isoliquiritin and liquiritin apioside,and accelerating the treatment of tanshinone I,formononetin,calycosin,acteoside and isoliquiritigenin.2.Comparative analysis of pharmacokinetics of bioactive compounds of QSKL in healthy rats and chronic heart failure ratsA rat model of chronic heart failure induced by isoprenaline(ISO)was established.Pharmacokinetic research methods were used to compare and analyze pharmacokinetic characteristic of the bioactive compounds in QSKL in healthy rats and chronic heart failure rats.The results showed that there were no significant differences in the bioavailability of tanshinone I,cryptotanshinone,liquiritigenin,isoliquiritigenin,formononetin,and calycosin in rats before and after modeling.In the chronic heart failure rats body,the bioavailability of glycyrrhetinic acid was increased,the bioavailability of salvianolic acid A,chlorogenic acid,acteoside glycyrrhizic acid,liquiritin,isoliquiritin,liquiritin apioside,benzoylaconine,benzoylhypacoitine and benzoylmesaconine was reduced,the duration of dihydrotanshinone I was prolonged and the absorption rate of liquiritin,isoliquiritin,benzoylaconine and benzoylhypacoitine was accelerated.3.Tissue distribution of the main bioactive compounds of QSKL in healthy rats and chronic heart failure ratsA model of chronic heart failure in rats was established using ISO,and the distribution of bioactive compounds in the organs of healthy rats and CHF rats was quantitatively analyzed using LC-MS.The results showed that salvianolic acid A,7 GGL compounds and 3 ACD compounds were absorbed and utilized by various organs of rats.SMB and SNH compounds are mainly present in the blood,APS compounds are higher in the liver than other organs,and LJT compounds are mainly found in blood and liver.The bioavailability of salvianolic acid A,cryptotanshinone,formononetin,calycosin,cryptochlorogenic acid,glycyrrhetinic acid,liquiritigenin,isoliquiritigenin,liquiritin and isoliquiritin in the liver of heart failure rats was higher than health rat.It shows that these compounds are more likely to exert drug effects in the liver of heart failure rats.It is speculated that the liver is the main target organ for QSKL to exert drug effects. |
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