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Published in: Chinese Medicine 1/2024

Open Access 01-12-2024 | Herpes Virus | Research

Prunella vulgaris polysaccharide inhibits herpes simplex virus infection by blocking TLR-mediated NF-κB activation

Authors: Xuanlei Zhong, Yibo Zhang, Man Yuan, Lin Xu, Xiaomei Luo, Rong Wu, Zhichao Xi, Yang Li, Hongxi Xu

Published in: Chinese Medicine | Issue 1/2024

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Abstract

Background

Prunella vulgaris polysaccharide extracted by hot water and 30% ethanol precipitation (PVE30) was reported to possess potent antiviral effects against herpes simplex virus (HSV) infection. However, its anti-HSV mechanism has not yet been fully elucidated.

Purpose

This study aimed to investigate the potential mechanisms of PVE30 against HSV infection.

Methods

Antiviral activity was evaluated by a plaque reduction assay, and the EC50 value was calculated. Immunofluorescence staining and heparin bead pull-down assays confirmed the interactions between PVE30 and viral glycoproteins. Real-time PCR was conducted to determine the mRNA levels of viral genes, including UL54, UL29, UL27, UL44, and US6, and the proinflammatory cytokines IL-6 and TNF-α. The protein expression of viral proteins (ICP27, ICP8, gB, gC, and gD), the activity of the TLR-NF-κB signalling pathway, and necroptotic-associated proteins were evaluated by Western blotting. The proportion of necroptotic cells was determined by flow cytometric analysis.

Results

The P. vulgaris polysaccharide PVE30 was shown to compete with heparan sulfate for interaction with HSV surface glycoprotein B and gC, thus strongly inhibiting HSV attachment to cells. In addition, PVE30 downregulated the expression of IE genes, which subsequently downregulated the expression of E and L viral gene products, and thus effectively restricted the yield of progeny virus. Further investigation confirmed that PVE30 inhibited TLR2 and TLR3 signalling, leading to the effective suppression of NF-κB activation and IL-6 and TNF-α expression levels, and blocked HSV-1-induced necroptosis by reducing HSV-1-induced phosphorylation of MLKL.

Conclusion

Our results demonstrate that the P. vulgaris polysaccharide PVE30 is a potent anti-HSV agent that blocks TLR-mediated NF-κB activation.

Graphical Abstract

Appendix
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Metadata
Title
Prunella vulgaris polysaccharide inhibits herpes simplex virus infection by blocking TLR-mediated NF-κB activation
Authors
Xuanlei Zhong
Yibo Zhang
Man Yuan
Lin Xu
Xiaomei Luo
Rong Wu
Zhichao Xi
Yang Li
Hongxi Xu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Chinese Medicine / Issue 1/2024
Electronic ISSN: 1749-8546
DOI
https://doi.org/10.1186/s13020-023-00865-y

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