Anti-cerebral ischemia mechanisms of baicalein and genipin based on network pharmacology / 中草药

ABSTRACT

Objective: Using network pharmacology and molecular docking technology along with scutellarein (SE) as a reference, this study predicted the anti-cerebral ischemia targets of both baicalein (BE) and genipin (GE). It is hoped that these will provide a reference for clinical prevention and development of ischemic diseases. Methods: SE, BE and GE targets were predicted using TCMSP, Swiss Target Prediction, Stitch database search and literature mining methods. Targets related to cerebral ischemia diseases could be predicted by DisGeNET, CTD, NCBI Gene, OMIM, DrugBank and PharmGkb databases. Cytoscape 3.3.0 was used to construct the small molecule-target network. GO function enrichment and KEGG pathway analysis of SE, BE and GE specific anti-cerebral ischemia targets were analyzed with the DAVID database. Autodock Vina software was used for molecular docking, testing the binding energy of BE, GE and SE to targets of cerebral ischemia. The optimal target protein was selected according to the binding energy and inhibition concentration of receptor and ligand. Results: A total of 30 potential targets of SE, 59 potential targets of BE and 35 potential targets of GE were found. Common anti-cerebral ischemia targets of SE and BE were PIK3CG, CYP1A2, VEGFA, ALOX5 and PTGS2, while common anti-cerebral ischemia targets of SE and GE were PTGS2. Molecular docking results demonstrated that the binding energy and inhibitory concentration of receptor PTGS2 to the three drugs were relatively low. Enrichment of GO function showed that common targets of BE-SE were mainly distributed in cytoplasm, organelle membrane, endoplasmic reticulum and other elements. These elements had binding functions with metal ions and cations, catalytic and oxidoreductase activities, and they participated in cell lipid, carboxylic acid, oxygenic acid, organic acid metabolism and fatty acid synthesis. Results: of the KEGG analysis demonstrated that receptor PTGS2 mainly acted on the arachidonic acid metabolism pathway and the vascular endothelial growth factor signaling pathway. A combination of BE and GE functioned in the treatment of cerebral ischemia disease by inhibiting expression of PTGS2 (COX-2) and vascular endothelial growth factor protein, thus reducing brain injury caused by inflammatory factors and improving the permeability of the blood brain barrier (BBB). Conclusion: This study predicted potential targets of BE and GE compatibility in the treatment of cerebral ischemia diseases and preliminarily verified mechanisms of action in the treatment of cerebral ischemia diseases. It provides valuable data for further study into the mechanisms of BE and GE compatibility for the treatment of cerebral ischemia as well as developing a basis for the next synthesis of new derivatives.