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柳参胶囊通过抑制 NF-κB 信号通路显示出对新型冠状病毒 SARS-CoV-2 的抗病毒和抗炎能力。

Liu Shen capsule shows antiviral and anti-inflammatory abilities against novel coronavirus SARS-CoV-2 via suppression of NF-κB signaling pathway.

机构信息

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, postcode, PR China.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, postcode, PR China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), PR China.

出版信息

Pharmacol Res. 2020 Aug;158:104850. doi: 10.1016/j.phrs.2020.104850. Epub 2020 Apr 30.

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread worldwide through person-to-person contact, causing a public health emergency of international concern. At present, there is no specific antiviral treatment recommended for SARS-CoV-2 infection. Liu Shen capsule (LS), a traditional Chinese medicine, has been proven to have a wide spectrum of pharmacological properties, such as anti-inflammatory, antiviral and immunomodulatory activities. However, little is known about the antiviral effect of LS against SARS-CoV-2. Herein, the study was designed to investigate the antiviral activity of SARS-CoV-2 and its potential effect in regulating the host's immune response. The inhibitory effect of LS against SARS-CoV-2 replication in Vero E6 cells was evaluated by using the cytopathic effect (CPE) and plaque reduction assay. The number of virions of SARS-CoV-2 was observed under transmission electron microscope after treatment with LS. Proinflammatory cytokine expression levels upon SARS-CoV-2 infection in Huh-7 cells were measured by real-time quantitative PCR assays. The results showed that LS could significantly inhibit SARS-CoV-2 replication in Vero E6 cells, and reduce the number of virus particles and it could markedly reduce pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-8, CCL-2/MCP-1 and CXCL-10/IP-10) production at the mRNA levels. Moreover, the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blot and it was found that LS could inhibit the expression of p-NF-κB p65, p-IκBα and p-p38 MAPK, while increasing the expression of IκBα. These findings indicate that LS could inhibit SARS-CoV-2 virus infection via downregulating the expression of inflammatory cytokines induced virus and regulating the activity of NF-κB/MAPK signaling pathway in vitro, making its promising candidate treatment for controlling COVID-19 disease.

摘要

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)通过人与人之间的接触在全球范围内传播,引发了国际关注的公共卫生紧急事件。目前,尚无针对 SARS-CoV-2 感染的特定抗病毒治疗方法。刘申胶囊(LS)是一种中药,已被证明具有广泛的药理作用,如抗炎、抗病毒和免疫调节作用。然而,对于 LS 对 SARS-CoV-2 的抗病毒作用知之甚少。在此,本研究旨在研究 LS 对 SARS-CoV-2 的抗病毒活性及其对调节宿主免疫反应的潜在作用。通过细胞病变效应(CPE)和蚀斑减少测定法评估 LS 对 Vero E6 细胞中 SARS-CoV-2 复制的抑制作用。用 LS 处理后,在透射电子显微镜下观察 SARS-CoV-2 病毒粒子的数量。通过实时定量 PCR 测定法测量 SARS-CoV-2 感染后 Huh-7 细胞中促炎细胞因子的表达水平。结果表明,LS 可显著抑制 Vero E6 细胞中 SARS-CoV-2 的复制,并减少病毒颗粒的数量,同时还能显著降低促炎细胞因子(TNF-α、IL-6、IL-1β、IL-8、CCL-2/MCP-1 和 CXCL-10/IP-10)的 mRNA 水平。此外,通过 Western blot 检测 NF-κB/MAPK 信号通路中的关键蛋白的表达,发现 LS 可抑制 p-NF-κB p65、p-IκBα 和 p-p38 MAPK 的表达,同时增加 IκBα 的表达。这些结果表明,LS 可通过下调诱导病毒的炎症细胞因子的表达和调节 NF-κB/MAPK 信号通路的活性来抑制 SARS-CoV-2 病毒感染,使其成为控制 COVID-19 疾病的有前途的候选治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a51a/7192119/4751782372d4/ga1_lrg.jpg

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