Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.
Phytomedicine. 2014 May 15;21(6):857-65. doi: 10.1016/j.phymed.2014.01.013. Epub 2014 Mar 11.
Several essential oils exert in vitro activity against bacteria and viruses and, among these latter, herpes simplex virus type 1 (HSV-1) is known to develop resistance to commonly used antiviral agents. Thus, the effects of the essential oil derived from Mentha suaveolens (EOMS) and its active principle piperitenone oxide (PEO) were tested in in vitro experimental model of infection with HSV-1. The 50% inhibitory concentration (IC50) was determined at 5.1μg/ml and 1.4μg/ml for EOMS and PEO, respectively. Australian tea tree oil (TTO) was used as control, revealing an IC50 of 13.2μg/ml. Moreover, a synergistic action against HSV-1 was observed when each oil was added in combination with acyclovir. In order to find out the mechanism of action, EOMS, PEO and TTO were added to the cells at different times during the virus life-cycle. Results obtained by yield reduction assay indicated that the antiviral activity of both compounds was principally due to an effect after viral adsorption. Indeed, no reduction of virus yield was observed when cells were treated during viral adsorption or pre-treated before viral infection. In particular, PEO exerted a strong inhibitory effect by interfering with a late step of HSV-1 life-cycle. HSV-1 infection is known to induce a pro-oxidative state with depletion of the main intracellular antioxidant glutathione and this redox change in the cell is important for viral replication. Interestingly, the treatment with PEO corrected this deficit, thus suggesting that the compound could interfere with some redox-sensitive cellular pathways exploited for viral replication. Overall our data suggest that both EOMS and PEO could be considered good candidates for novel anti-HSV-1 strategies, and need further exploration to better characterize the targets underlying their inhibition.
几种精油对细菌和病毒具有体外活性，而在这些病毒中，单纯疱疹病毒 1 型（HSV-1）已知对常用抗病毒药物产生耐药性。因此，测试了源自薄荷（EOMS）及其活性成分胡椒酮氧化物（PEO）的精油在感染 HSV-1 的体外实验模型中的作用。EOMS 和 PEO 的 50％抑制浓度（IC50）分别为 5.1μg/ml 和 1.4μg/ml。茶树油（TTO）用作对照，其 IC50 为 13.2μg/ml。此外，当每种油与阿昔洛韦联合添加时，观察到对 HSV-1 的协同作用。为了找出作用机制，在病毒生命周期的不同时间将 EOMS、PEO 和 TTO 添加到细胞中。通过产量减少测定获得的结果表明，两种化合物的抗病毒活性主要归因于病毒吸附后的作用。事实上，当在病毒吸附期间或在病毒感染之前进行预处理时，用细胞处理时未观察到病毒产量降低。特别是，PEO 通过干扰 HSV-1 生命周期的后期步骤发挥了强烈的抑制作用。HSV-1 感染会导致氧化应激状态，导致主要细胞内抗氧化剂谷胱甘肽耗竭，这种细胞内的氧化还原变化对于病毒复制很重要。有趣的是，PEO 的治疗纠正了这种不足，因此表明该化合物可能会干扰一些用于病毒复制的氧化还原敏感的细胞途径。总的来说，我们的数据表明，EOMS 和 PEO 都可以被认为是新型抗 HSV-1 策略的良好候选者，需要进一步探索以更好地阐明其抑制作用的靶标。
