The anti-HIV-1 activity and mechanisms of Euonymus fortunei extract
Objective To investigate the anti-human immunodeficiency virus-1(HIV-1)activity of Euonymus fortunei extract and its mechanism,providing a theoretical basis for the research and development of traditional Chinese herbal resources in the treatment of acquired immunodeficiency syndrome(AIDS).Methods The peripheral blood mononuclear cells(PBMCs)-HIV-1bal cell model system was used as the experimental model,and the effect of Euonymus fortunei extract on the cell activity and anti-HIV-1 activity of PBMCs was investigated by CellTiter-Glo assay and HIV-1 p24 antigen assay.Additionally,the mechanism of anti-HIV-1 action of Euonymus fortunei extract was determined through the time-of-addition assay and HIV-1 enzymatic assays.Results In the PBMCs-HIV-1bal cell model,Euonymus fortunei extract showed no significant effect on cellular activity at the highest concentration,with a median cytotoxic concentration(CC50)>40 μg/mL.Within the non-cytotoxic concentration range,the level of HIV-1baldecreased with the increase of the extract concentration,with the IC50=0.084 μg/mL,and the SI>476.19.Time-of-addition assay revealed that Euonymus fortunei extract had the highest inhibitory activity on HIV-1IIIB when it was added to cells at the same time as the virus,and the inhibitory rate of HIV-1 activity decreased at 2 h and gradually lost its inhibitory effect on the virus at 18-24 h,similar to the known HIV entry inhibitor Enfuvirtid(T-20).Key HIV-1 enzyme activity experiments found that the extract had no significant inhibitory effect on reverse transcriptase activity but exhibited dose-dependent inhibition of integrase activity,with integrase activity decreasing with increasing extract concentration(IC50=0.18 μg/mL);The extract could inhibit the activity of HIV-1 protease in a certain concentration range(IC50=39.18 μg/mL).Conclusions In this study,it was found that Euonymus fortunei extract has a strong inhibitory activity against HIV-1 activity,which may exert anti-HIV-1 effects by acting on viral entry into cells and inhibiting integrase activity,and has a good application prospect in the research and development of multi-target new drugs against HIV-1.
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