The Effect And Mechanism Of Oleanolic Acid Against HSV-1

Objective:To isolate and purify Oleanolic acid compounds from benzoin in vivo and in vitro anti-HSV-1 activity,and to explore the antiviral mechanism,so as to lay a theoretical foundation for the development of new anti-HSV-1 drugs.Methods:The oleanolic acid toxicity was detected on different cells by the CCK8experiment.The anti-HSV-1 activity of oleanolic acid was detected by plaque subtraction test,viral genomic DNA copy number,virus titer and other methods.Drugs were added at different time points.The role of Oleanolic acid was explored.A plasmid was constructed on the basis of determining that Oleanolic acid can affect the helicase-priming enzyme complex.The potential target of Oleanolic acid was determined through si RNA interference and overexpression.Finally,the anti-HSV-1 activity of Oleanolic acid in vivo was explored through the mouse skin shingles model.Results:Oleanolic acid was not very toxic to Vero cells and Ha Ca T cells,with IC₅₀values of 39.05μM and 37.06μM respectively.Plaque subtraction experiments and virus titers and WB results showed that Oleanolic acid was anti-HSV-1 on different cells and oleanolic acid also has good antiviral activity against ACV resistant strains.In addition,mechanism studies have found that oleanolic acid exhibits better anti-HSV-1 activity in the immediate early stage.Further research has found that oleanolic acid can significantly down-regulate the expression level of gyrase-priming enzyme complex m RNA,and found that UL8 is a potential target for oleanolic acid.Finally,in vivo anti-HSV-1 experiments showed that oleanolic acid can significantly improve the herpes zoster caused by HSV-1 in mice.Oleanolic acid has anti-HSV-1 activity both in vivo and in vitro.Conclusions:Oleanolic acid has antiviral activity against normal HSV-1 strains and ACV resistant strains.Oleanolic acid also has good anti-HSV-1 activity in vivo.Mechanism studies have shown that Oleanolic acid exerts antiviral activity through UL8.UL8 is potential targets for oleanolic acid.