Anti-ischemic Stroke Effect Of C1(Gentianine) Isolated From Gentiana Macrophylla Radix Through Network Pharmacology(Docking)

Objective:Clinical observation found that ischemic stroke is more common than hemorrhagic stroke,accounting for about 87%of all cases,and has become the focus of most research.Most ischemic strokes are due to blood clots or embolisms that block the main arteries of the brain.About one-third of patients with ischemic stroke in cities in eastern China have received TCM treatment.Chinese medicine has played a good protective role against ischemic stroke.In ischemic stroke,the transformation of ECM in the inflammatory process after tissue injury is mainly attributed to the expression of MMPs.Gentianine is an MMP inhibitory compound that can effectively resist inflammation and oxidative reactions.In this project,we use network pharmacology-related technologies to explore the effects of Gentianine on cerebral ischemic symptoms.Methods:First,the following three online tools(Protox,Swiss-ADME,Molinspiration)were used to find the bioactivity score,pharmacokinetic properties,toxicity and molecular properties of Gentianine.Network pharmacology approach was used by gathering drug targets and pharmacology information from STITCH database.GO term enrichment analysis was used to find out biological mechanism and signaling pathway and then Cytoscape was used to visualize the molecular level mapping of pathways.Finally,molecular docking was performed.The results showed that Gentianine was docked with MMP2 and MMP9 respectively.Results:The results of pharmacokinetic properties,toxicity and biological activity scores showed that Gentianine can enter the human body safely and non-toxically.The network pharmacology approach,PPI-network shows 5 protein targets(IL6,PTGS2,COX5A,PPARA,GLUTAMATE)of Gentianine associated with IS.While GO analysis of Gentianine gives two Go-term pathways in association with IS.The docking results of Gentianine and MMP2 produced 6 hydrogen bonding interactions at THR227,ALA220,ILE164,ALA165,GLU202 with the highest docking score of-6.54,Ref rmsd of 77.61A and Ki value of-16.1 uM.However,Gentianine with MMP9 produced 5 hydrogen bonding interactions at ALA417,ARG424,THR426,PHE107,PRO415 with a high docking score-6.43,Ref rmsd 75.28A and Ki value of 19.46uM,thus confirming the high Inhibitory activity.Conclusion:Gentianine might be an effective pharmaceutical and pharmacologically active compound for the treatment of ischemic stroke.