Carvacrol inhibits the excessive immune response induced by influenza virus A via suppressing viral replication and TLR/RLR pattern recognition
Carvacrol inhibits the excessive immune response induced by influenza virus A via suppressing viral replication and TLR/RLR pattern recognition
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香芹酚通过抑制病毒复制和 TLR/RLR 模式识别来抑制甲型流感病毒诱导的过度免疫反应。
DOI：
10.1016/j.jep.2020.113555
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发表时间：
2021-01-15
影响因子：
5.4
通讯作者：
Chen, Xiao-yin
中科院分区：
文献类型：
--
作者：
Zheng, Ke;Wu, Si-zhi;Chen, Xiao-yin
民族药理学相关性：香芹酚是一种来自Mosla chinensis Maxim的单萜酚，是一种常见的中草药。它最重要的药理是发汗祛邪。是辛甲香茹饮中药复方中的君子药，主要用于治疗夏季湿寒感冒，包括甲型流感病毒感染。 研究目的：我们的前期研究证实，辛甲香茹饮能够抑制甲型流感病毒感染小鼠的急性肺损伤。有一些报道表明香芹酚具有高抗菌活性，可用于多种产品保存，但很少有研究涉及其对病毒感染的影响。本研究的目的是揭示香芹酚的抗病毒作用。香芹酚是Mosla chinensis Maxim中的主要成分。 材料与方法：首先将C57BL/6小鼠分组，鼻内注射FM1病毒，构建病毒感染模型。用利巴韦林和香芹酚治疗5天后，对所有小鼠实施安乐死，并立即获取标本。采用组织学、流式细胞术和Meso Scale Discovery (MSD)分析分析肺组织病理变化、细胞因子表达水平以及CD4(+) T细胞亚群的分化和比例，Western blot和qRT-PCR检测相关蛋白和mRNA的表达。结果：香芹酚减轻肺组织损伤，CD4(+) T细胞中Th1、Th2、Th17和Treg比例以及Th1/Th2 和 Th17/Treg 细胞的相对比例。香芹酚抑制炎症相关细胞因子的表达，包括 IFN-γ、IL-2、IL-4、IL-5、IL-12 和 TNF-α、IL-1、IL-10、IL-6。与VC组小鼠相比，香芹酚治疗小鼠的TLR7、MyD88、IRAK4、TRAK6、NF-κB、RIG-I、IPS-I和IRF mRNA水平降低。此外，VC组中RIG-I、MyD88和NF-κB蛋白的总表达显着升高，而利巴韦林或香芹酚治疗组中RIG-I、MyD88和NF-κB蛋白的总表达明显降低。结论：这些结果表明香芹酚是治疗甲型流感病毒感染引起的过度免疫反应的潜在替代疗法，大蝽的抗寒作用可能依赖于香芹酚的抗病毒作用。
Ethnopharmacological relevance: Carvacrol, a monoterpene phenol from Mosla chinensis Maxim, which is a commonly Chinese herbal medicine. The most important pharmacology of it is dispelling exogenous evils by increasing perspiration. And it is the gentleman medicine in the Chinese herbal compound prescription of Xin-Jia-Xiang-Ru-Yin, mainly for the treatment of summer colds with dampness including influenza virus A infection.Aim of the study: Our preliminary study verified that the Xin-Jia-Xiang-Ru-Yin could inhibit acute lung injury of mice with influenza virus A infection. And there have been some reports implicating the high antimicrobial activity of carvacrol for a wide range of product preservation, but little research including the effects of it on viral infection. The aim of this study was to reveal the antiviral effects of carvacrol, the main constituent in Mosla chinensis Maxim.Materials and methods: Initially, C57BL/6 mice were grouped and intranasally administered FM1 virus to construct viral infection models. After treatment with ribavirin and carvacrol for 5 days, all mice were euthanized, and specimens were immediately obtained. Histology, flow cytometry and Meso Scale Discovery (MSD) analysis were used to analyze pathological changes in lung tissue, the expression levels of cytokines and the differentiation and proportion of CD4(+) T cells subsets, while Western blot and qRT-PCR were used to detect the expression of related proteins and mRNA.Results: Carvacrol attenuated lung tissue damage, the proportions of Th1, Th2, Th17 and Treg in CD4(+) T cells and the relative proportions of Th1/Th2 and Th17/Treg cells. Carvacrol inhibited the expression of inflammation-associated cytokines including IFN-gamma, IL-2, IL-4, IL-5, IL-12 and TNF-alpha, IL-1, IL-10, IL-6. Decreased levels of TLR7, MyD88, IRAK4, TRAK6, NF-kappa B, RIG-I, IPS-I and IRF mRNA in carvacrol-treated mice were observed comparing to the mice in VC group. Further, the total expression of RIG-I, MyD88 and NF-kappa B proteins had increased significantly in the VC group but reduced obviously in the group treated with ribavirin or carvacrol.Conclusions: These results indicate that carvacrol is a potential alternative treatment for the excessive immune response induced by influenza virus A infection, the cold-fighting effect of Mosla chinensis Maxim may depend on the anti-virus of carvacrol.