Integrating drug-likeness and network target to analyze the potential molecular mechanism of Danggui Buxue Jiawei decoction in the prevention and treatment of diabetic retinopathy / 国际药学研究杂志

ABSTRACT

Objective: Integrating drug-likeness and network targets to preliminarily predict and explore the targets and pathways of Danggui Buxue Jiawei decoction(DBJD)in the prevention and treatment of diabetic retinopathy(DR). Methods: The chemical constituents of DBJD were identified by UPLC-Q-TOF/HRMS E analytical techniques. The related websites were used to esti mate the drug-likeness for all identified constituents. Then, for the selected drug-like constituents, targets-predicting was carried out on PharmMapper, and the targets for DR were searched by CTD, TTD and GeneCards. The component-target and disease-target net works were integrated to establish a large network, and core targets were searched on the basis of the DC, CC and BC values of the large network. Moreover, indirect targets were further searched on the basis of the core targets. Then, an all potential targets-related network was constructed and related key targets were searched by the constructed network. The key targets were verified by docking with the related components. Gene ontology(GO)biological analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Reactome pathway analysis were carried out on all potential targets. Eventually, a large Prescription-Medicinal material-Component-Direct target-Indirect target-Pathway integrated network was established for the DBJD studies. Results: A total of 55 chemical constituents were identified by UPLC-Q-TOF/HRMS E. Among them, 33 components were selected by the drug-likeness esti mation. The core targets consisted of 36 targets, and 20 indirect targets were obtained by relating with the core targets. By comparing de gree values, 6 key targets were established AKT1, MAPK3, VEGFA, INS, MAPK1 and CASP3. In molecular docking tests, these key targets showed good binding activities with tanshinone, salvianolic acid B, ginsenoside Rg 1, notoginsenoside R 1, tanshinone Ⅱ A and other quality control components. Pathway analysis suggested that DBJD could likely interfere with the diabetic retinopathy by regulating oxidative stress, inflammatory factors and sugar metabolism. Conclusion: Accurate prediction of the action mechanism of complex Chinese medicinal ingredients based on the drug-likeness and network targets may be helpful to improve the blindness in relat ed research and accelerate the research process in modernization of traditional Chinese medicine. In this study, the molecular mecha nism of DBJD for the prevention and treatment of DR is preliminarily investigated and discussed, which could provide a valuable refer ence for future in-depth study.