ABSTRACT
Objective: The quality markers of Poria cocos were identified based on the “in vitro-in vivo” multidimensional chemical group associated network and in vivo pharmacokinetics, and the mass spectrometry method for quantitative detection of quality markers was established to evaluate the quality of P. cocos. Methods: A quantitative analysis method of triterpenoids in P. cocos was established by ultra-high performance liquid chromatography-triple quadruple tandem mass spectrometry (UHPLC-MS/MS) while dioscin was chosen as internal reference substance. The pharmacokinetic curves of active ingredients in vivo were drawn. Seven quality markers of P. cocos including dehydrotumulosic acid, tumulosic acid, and poricoic acid B were identified based on the results of pharmacokinetics. The content of high content components and quality markers in 10 batches of P. cocos were detected and used as variables for cluster analysis of 10 batches of P. cocos. Results: There were differences in the results of clustering analysis with different indexes as variables in evaluating the quality of P. cocos. Conclusion: To a certain extent, the method of quality control of P. cocos with high content components is one-sided. In order to comprehensively and accurately control the quality of P. cocos, it is necessary to take into full account the in vivo and in vitro changes and the in vivo dynamic process of P. cocos composition, and select the effective quality markers related to its pharmacodynamics for its quality control.
ABSTRACT
Objective: To explore the mechanism of Leigongteng Pian(Tripterygium wilfordii tablets)for the treatment of rheumatoid arthritis(RA)based on chemomics and network pharmacology. Method: UPLC-Q-TOF/HRMS was used to analyze the chemical constituents of Tripterygium wilfordii tablets under the positive and negative ion modes. Thereafter,the ingredient targets of Tripterygium wilfordii tablets were predicted by Swiss Target Prediction and Pharm- Mapper databases,and the targets of RA diseases were obtained by Traditional Chinese Medicine Systems Pharmacology (TCMSP),Therapeutic Target Database(TTD)and Comparative Toxicogenomics Database(CTD). By taking the inter-section of ingredient targets and disease targets,the direct common targets of Tripterygium wilfordii tablets for the treat- ment of rheumatoid arthritis were obtained. Then the GeneMANIA database was used to obtain indirect targets,and the software of Cytoscape 3.7.1 was used to construct the protein-protein interaction(PPI)networks of potential targets,by which the key targets were screened. Enrichment of gene function and pathways of all potential targets were conducted by Gene Ontology(GO)database and Kyoto Encyclopedia of Genes and Genomes(KEGG)database to explore the mecha- nism of Tripterygium wilfordii tablets for the treatment of rheumatoid arthritis. Results: Thirtyone chemical constituents of Tripterygium wilfordii tablets were screened out and sixtysix potential targets were predicted. Twentyseven active com- ponents in the Tripterygium wilfordii tablets might be important components for the treatment of rheumatoid arthritis as in- dicated by the reverse screening. At the same time,five core targets were screened out,which might be involved in the key pathways that actively participate in the intervention and adjustion of rheumatoid arthritis. Conclusion: In this study,we found that the active components in Tripterygium wilfordii tablets could exert important biological effects via multiple targets and pathways,and these targets and pathways are all involved with the inflammation and immune regula- tion of RA.
ABSTRACT
Objective To investigate the anti-inflammatory mechanism of the alkaloids in Dengtaiye Tablets (DTYT) based on the network pharmacology and chemomics. Methods The main indole alkaloids in the DTYT from Folium Alstoniae Scholaris were identified by UPLC-Q/TOF. The network pharmacology coupled with virtual docking technology and bioinformatics analysis were carried out for screening the key protein targets and pathways. Western blotting was utilized for evaluating the phosphorylation level of the primary node proteins in BEAS-2B cells inflammatory model induced by LPS. Results Twelve indole alkaloids were found in DTYT extract, which act on different protein targets, such as PDPK1 (PDK1), MAPK1 (ERK2), and MAPK8 (JNK1) respectively, and reduce the level of ERK2, JNK1, and IKK phosphorylation induced by LPS. Conclusion As the Q-markers of anti-inflammatory, the indole alkaloids contained in DTYT inhibited the PDK1/AKT/NF-κB and MAPK pathways, which present potential molecular mechanisms for the treatment of chronic bronchitis of DTYT.