RESUMEN
AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.
RESUMEN
AIM: The main chemical components of Yufang Fangji II (Hubei Fang) of COVID-19 were studied systematically and combined with network pharmacology to provide a reference for the study of its effective substances. METHODS: Ultra high-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-Q-TOF/MS) was applied to identify the absorbed components of the prescription in rat plasma. TCMSP database and Swiss Target Prediction data platform were used to predict the target of the identified blood components, and network visualization software Cytoscape 3.7.2 was used draw the association network diagram, and GO enrichment analysis and KEGG pathway enrichment analysis were conducted for the key targets. With the help of CB-Dock online molecular docking platform, the molecular docking of key targets and blood entering compounds was carried out, and the docking combination with good affinity value was displayed by ligplot software to verify the preventive effect of Yufang Fangji II on COVID-19. RESULTS: A total of 52 chemical components identified in the prescription, in which 13 components were absorbed in the rat plasma as the prototype, and they were from Astragalus membranaceus, Atractylodes macrocephala, Saposhnikoviae Radix, Lonicerae Japonicae Flos, and Citri Reticulatae Pericarpium, respectively. These compounds were recognized to act on 17 core targets, including mapk3, TNF and other targets related to inflammation, MPO and other targets related to oxidative stress, VEGFR, KDR and other targets related to vascular endothelium. The results of molecular docking showed that the absorbed components had good binding activity with the key targets. CONCLUSION: Compounds in Yufang Fangji II are involved in regulating inflammation, oxidative stress, vascular and cellular physiological activities, which have preventive effects on COVID-19 through regulating IL-17, PI3K Akt, MAPK and other pathways.