二氢杨梅素通过 TLR9 依赖性抗炎途径对单纯疱疹病毒 1 的抑制作用。
Anti-HSV-1 effect of dihydromyricetin from Ampelopsis grossedentata via the TLR9-dependent anti-inflammatory pathway.
机构信息
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.
出版信息
J Glob Antimicrob Resist. 2020 Dec;23:370-376. doi: 10.1016/j.jgar.2020.10.003. Epub 2020 Nov 5.
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 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.
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.
目的
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。
方法
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。
结果
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。
结论
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。
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