Effect of Rhei Radix et Rhizoma and Eupolyphaga Steleophaga on liver protection mechanism based on pharmacokinetics and metabonomics

Objective:Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)and hydrogen nuclear magnetic resonance spectroscopy(^(1)H NMR),the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma(RhRR,Dahuang in Chinese),Eupolyphaga Steleophaga(EuS,Tubiechong in Chinese)combined with RhRR acting on acute liver injury were explored.Methods:Models of acute liver injury were established,and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS.The liver tissues of different groups of mice were analyzed by ^(1)H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.Results:Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups,and the absorption of free anthraquinone in RhRR increased after compatibility with EuS.In addition,the pathological state of acute liver injury in rats can selectively promote the absorption of emodin,chrysophanol,physcion and aloe emodin.Through 15 differential metabolites in the liver tissue of acute liver injury mice,it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid,alanine,aspartic acid and glutamic acid,and phosphoinositide.However,the regulation of RhRR was weaker than that of RhRR-EuS.Conclusion:For the first time,we studied the pharmacokinetics and metabolomics differences of RhRREuS and RhRR in rats and mice with acute liver injury,in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.

Metabolic regulation mechanism of Aconiti Radix Cocta extract in rats based on ^(1)H-NMR metabonomics

Objective:To establish a metabonomics research technique based on the combination of^(1)H-NMR and multivariate statistical analysis,so as to explore the metabolic regulation mechanism of Aconiti Radix Cocta extract(ARCE)in rat tissues and serum.Methods:SD rats were randomly divided into blank group,female group and male group.The^(1)H-NMR technique was used to collect the information of rat tissues and serum samples in each group.The principal component analysis(PCA),partial least squares discriminant analysis(PLS-DA)and other methods were used for data pattern recognition,so as to screen out potential differential metabolites and metabolic pathways,and then network analysis and KEGG database were used to analyze the relationship between metabolites,metabolic pathways and diseases.Results:The external features and^(1)H-NMR analysis showed that the sex of rats had no obvious effect on the drug action.A total of 15 potential differential metabolites and six metabolic pathways were screened out through data pattern recognition.Through network analysis and KEGG pathway analysis,three target diseases closely related to differential metabolites were found,and the metabolic pathway related to lung cancer was the central carbon metabolism of cancer.Conclusion:This study shows that Aconiti Radix Cocta(ARC)may regulate the energy metabolism of the body by influencing arginine synthesis,so as to play the roles of anti-inflammation,analgesia,anti-tumor and immune regulation.