Antiviral activity of mangiferin from the rhizome of Anemarrhena asphodeloides against herpes simplex virus type 1

Abstract

Objective: To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1 (HSV-1) from the rhizome of Anemarrhena asphodeloides. Methods: Bioassay-guided isolation was conducted to separate the active compound and its chemical structure was elucidated by spectral analysis. In vitro antiviral efficacy of active compound was detected by Cell Counting Kit-8 assay, plaque reduction assay, and fluorescence observation. RT-PCR was used to determine the viral load and the cytokine-related gene expression after HSV-1 infection. In vivo study was also conducted to further determine antiviral efficacy of an active compound against HSV-1. Results: An active compound was isolated and elucidated as mangiferin. Mangiferin significantly inhibited the replication of HSV-1 in Vero cells with a half maximal inhibitory concentration (IC50) of 64.0 mg/L. Time-of-addition and time-of-removal assays demonstrated that mangiferin could effectively inhibit the replication of HSV-1 in the early stage (8 h). UL12, UL42, and UL54 gene expression levels of HSV-1 in the 64 mg/L mangiferin-treated group were markedly reduced as compared with the HSV-1 group (P<0.01). Fluorescence observation showed that mangiferin attenuated the mitochondrial damage maintaining ΔΨm induced by HSV-1 in Vero cells. The expression of inflammatory factors TNF-α, IL- 1β, and IL-6 was remarkably increased in the virus-infected group as compared with that in the normal group (P<0.05), the levels of these inflammatory factors dropped after treatment with mangiferin. Mangiferin significantly decreased the viral load and attenuated the HSV-1-induced up-regulation of TNF-α, IL1β, and IL-6. The relative protection rate of HSV-1-infected mice could reach up to 55.5% when the concentration of mangiferin was 4 g/kg. Conclusions: Mangiferin exhibits promising antiviral activity against HSV-1 in vitro and in vivo and could be a potential antiviral agent for HSV-1.