Anti-HSV-1 effect of dihydromyricetin from Ampelopsis grossedentata via the TLR9-dependent anti-inflammatory pathway
| Autor: | Chunyang Shi, Wei Xiong, Wenqing Wang, Shuang-qi Gao, Hai-yun Zhou, Shuai Tong, Tong Lin, Yu-sheng Gong, Jianguo Fang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Ampelopsis Flavonols medicine.drug_class viruses 030106 microbiology Immunology ved/biology.organism_classification_rank.species Anti-Inflammatory Agents Herpesvirus 1 Human Pharmacology medicine.disease_cause Microbiology NF-κB Anti-inflammatory Virus 03 medical and health sciences 0302 clinical medicine In vivo Chlorocebus aethiops TNFα medicine Immunology and Allergy Animals Humans 030212 general & internal medicine Vero Cells ved/biology Chemistry Dihydromyricetin ICP HSV-1 QR1-502 Real-time polymerase chain reaction Herpes simplex virus Mechanism of action Toll-Like Receptor 9 Vero cell medicine.symptom Ampelopsis grossedentata |
| Zdroj: | Journal of Global Antimicrobial Resistance, Vol 23, Iss, Pp 370-376 (2020) |
| ISSN: | 2213-7173 |
| Popis: | Objectives Herpes simplex virus 1 (HSV-1) is one of the most prevalent viruses in humans worldwide. Owing to limited therapeutic options mainly with acyclovir (ACV) and analogues and the emergence of ACV-resistant strains, new drugs with different modes of action and low toxicity are required. The aim of this study was to determine the anti-HSV-1 effect and mechanism of action of the flavonoid compound dihydromyricetin (DHM) from Ampelopsis grossedentata. Methods The HSV-1 inhibitory effect of DHM was evaluated by measuring plaque formation and generation of progeny virus as well as expression of HSV-1-related genes in Vero cells. The molecular mechanism of the antiviral activity of DHM against HSV-1 was explored by real-time quantitative PCR and ELISA. Results DHM presented a significant inhibitory effect on HSV-1 plaque formation and generation of progeny virus, with an EC50 (50% effective concentration) of 12.56 μM in Vero cells. Furthermore, expression of HSV-1 immediate-early genes (ICP4 and ICP22), early genes (ICP8 and UL42) and late genes (gB, VP1/2) was decreased by DHM at concentrations of 16 μM and 32 μM. DHM specifically suppressed mRNA levels of Toll-like receptor 9 (TLR9), leading to inhibition of the inflammatory transcriptional factor NFκB and a decrease in TNFα. Conclusion These findings indicate that the effective inhibitory activity of DHM was achieved by suppressing TNFα production in a TLR9-dependent manner. Although further studies are needed to better characterise the activity of DHM in vivo, the results suggest this extract as a promising new anti-HSV-1 agent. |
| Databáze: | OpenAIRE |
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