Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, China.
Department of Neurosurgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China.
J Glob Antimicrob Resist. 2020 Dec;23:370-376. doi: 10.1016/j.jgar.2020.10.003. Epub 2020 Nov 5.
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.
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.
DHM presented a significant inhibitory effect on HSV-1 plaque formation and generation of progeny virus, with an EC (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.
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.
单纯疱疹病毒 1（HSV-1）是全球范围内最常见的人类病毒之一。由于主要使用阿昔洛韦（ACV）及其类似物的治疗选择有限，以及出现 ACV 耐药株，因此需要具有不同作用模式和低毒性的新药。本研究旨在确定从葡萄科蛇葡萄属（Ampelopsis grossedentata）中提取的类黄酮化合物二氢杨梅素（DHM）抗 HSV-1 的效果和作用机制。
通过测量空斑形成和病毒子代生成以及 Vero 细胞中 HSV-1 相关基因的表达，评估 DHM 对 HSV-1 的抑制作用。通过实时定量 PCR 和 ELISA 探索 DHM 对 HSV-1 的抗病毒活性的分子机制。
DHM 对 HSV-1 空斑形成和病毒子代生成具有显著的抑制作用，在 Vero 细胞中的 EC（50%有效浓度）为 12.56 μM。此外，DHM 在 16 μM 和 32 μM 浓度下可降低 HSV-1 的即刻早期基因（ICP4 和 ICP22）、早期基因（ICP8 和 UL42）和晚期基因（gB、VP1/2）的表达。DHM 特异性抑制 Toll 样受体 9（TLR9）的 mRNA 水平，从而抑制炎症转录因子 NFκB 并降低 TNFα。
这些发现表明，DHM 的有效抑制活性是通过 TLR9 依赖性方式抑制 TNFα 产生来实现的。尽管需要进一步研究以更好地描述 DHM 在体内的活性，但研究结果表明，该提取物是一种有前途的新型抗 HSV-1 药物。
