Anti-HSV-1 effect of dihydromyricetin from Ampelopsis grossedentata via the TLR9-dependent anti-inflammatory pathway

Objectives: Herpes simplex virus-1 (HSV-1) is one of the most prevalent viruses in human being worldwide and due to limited therapies mainly with acyclovir (ACV) and analogues and emergence of ACV resistant strains, the search for new drugs with different modes of action and low toxicity is required for public health. The aim of this study was to describe anti-HSV-1 effect and mechanism of flavonoid compound, dihydromyricetin (DHM).

Methods: HSV-1 inhibitory effect of DHM was evaluated by measurement of plague formation and generation of progeny virus, and expression of HSV-1-related genes on Vero cells. The molecular mechanism of DHM anti-viral activity on HSV-1 was explored by real-time quantitative PCR (RT-qPCR) and ELISA assay.

Results: DHM presented significant inhibitory effect on HSV-1 plague formation and generation of progeny virus, with EC50 value (50% effective concentration) of 12.56 μM on Vero cells. Furthermore, the expression of HSV-1 immediate-early genes (ICP4, ICP22 and ICP27), early genes (ICP8 and UL42) and late genes (gB, VP1/2) were decreased by DHM at concentrations of 16 and 32 μM. The present study found that DHM specifically suppressed the mRNA levels of toll like receptor 9 (TLR9), leading the inflammatory transcriptional factor NF-κB inhibition, and the TNF-α decrease.

Conclusion: These findings indicate that effective inhibitory activity of DHM performs were achieved by suppressing TNF-α production in a TLR9-dependent inflammatory response manner. Although further studies are needed to better characterize DHM activity in vivo, the results suggest this extract as a promising new anti-HSV-1 agent.

Keywords: Dihydromyricetin; HSV-1; ICP; NF-κB; TNF-α; Toll like receptor 9.