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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引起的过度免疫反应。

Carvacrol inhibits the excessive immune response induced by influenza virus A via suppressing viral replication and TLR/RLR pattern recognition.

机构信息

College of Traditional Chinese Medicine, Jinan University, Guangzhou, China; The Hospital of the People's Liberation Army's 83rd Group, Xinxiang, China.

College of Traditional Chinese Medicine, Jinan University, Guangzhou, China.

出版信息

J Ethnopharmacol. 2021 Mar 25;268:113555. doi: 10.1016/j.jep.2020.113555. Epub 2020 Nov 2.

DOI:10.1016/j.jep.2020.113555
PMID:33152425
Abstract

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-γ, IL-2, IL-4, IL-5, IL-12 and TNF-ɑ, IL-1, IL-10, IL-6. Decreased levels of TLR7, MyD88, IRAK4, TRAK6, NF-κB, 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-κB 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.

摘要

民族药理学相关性

香薷中的香芹酚是一种单萜酚类化合物,它是一种常见的中草药。其最重要的药理学作用是通过发汗来祛除外邪。它是中药复方新加香薷饮中的君子药,主要用于治疗夏季感冒挟湿,包括流感病毒 A 感染。

研究目的

我们的初步研究证实,新加香薷饮可抑制流感病毒 A 感染所致的小鼠急性肺损伤。已有一些报道表明香芹酚具有很高的抗菌活性,可广泛用于产品保鲜,但对其抗病毒作用的研究甚少。本研究旨在揭示香薷中主要成分香芹酚的抗病毒作用。

材料和方法

首先,将 C57BL/6 小鼠分组,经鼻腔给予 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,所有小鼠安乐死,立即获取标本。采用组织学、流式细胞术和 Meso Scale Discovery(MSD)分析方法分析肺组织的病理变化、细胞因子的表达水平以及 CD4 T 细胞亚群的分化和比例,同时采用 Western blot 和 qRT-PCR 检测相关蛋白和 mRNA 的表达。

结果

香芹酚减轻了肺组织损伤,CD4 T 细胞中 Th1、Th2、Th17 和 Treg 的比例以及 Th1/Th2 和 Th17/Treg 细胞的相对比例。香芹酚抑制了炎症相关细胞因子 IFN-γ、IL-2、IL-4、IL-5、IL-12 和 TNF-ɑ、IL-1、IL-10、IL-6 的表达。与 VC 组相比,香芹酚处理组小鼠 TLR7、MyD88、IRAK4、TRAK6、NF-κB、RIG-I、IPS-I 和 IRF mRNA 的表达水平降低。此外,与 VC 组相比,利巴韦林或香芹酚治疗组总 RIG-I、MyD88 和 NF-κB 蛋白表达明显增加。

结论

这些结果表明,香芹酚可能是治疗流感病毒 A 感染引起的过度免疫反应的一种潜在替代疗法,香薷的抗感冒作用可能依赖于香芹酚的抗病毒作用。

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