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大冤饮减轻人冠状病毒229E诱导的肺炎症状并调节Ras/Raf1/MEK/ERK信号通路。

Dayuan Yin alleviates symptoms of HCoV-229E-induced pneumonia and modulates the Ras/Raf1/MEK/ERK pathway.

作者信息

Li Rui, Zhang Wen, Huang Bei, Sun Guotong, Xie Yifei, Song Junke, Wang Shumei, Du Guanhua

机构信息

Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Guangdong Pharmaceutical University, Guangzhou, 510006, China.

出版信息

Nat Prod Bioprospect. 2024 Nov 4;14(1):58. doi: 10.1007/s13659-024-00474-8.

Abstract

Viral pneumonia is characterized by inflammation in the lungs triggered by respiratory viruses. Dayuan Yin (DYY), a traditional Chinese medicine formula known for treating infectious diseases, is hypothesized to offer therapeutic benefits in treating viral pneumonia, although its specific molecular impacts remain understudied. This study aimed to evaluate the therapeutic effects of DYY in mitigating HCoV-229E virus-induced pneumonia in mice. This study employed an HCoV-229E virus-infected mouse model to investigate the therapeutic potential and underlying molecular mechanisms of DYY on virus-induced pneumonia. The respiratory function and organ indices post-treatment were assessed. Lung tissue and tracheal lesions were evaluated via immunohistochemistry. Spleen immune cell composition was analyzed using flow cytometry. Inflammatory cytokines and viral loads were quantified using hypersensitive multiplex electrochemiluminescence method and PCR analysis, respectively. The expression levels of MAS1, Ras, Raf1, MEK1/2, and ERK1/2 in lung tissues were determined through western blot analysis. DYY significantly improved respiratory function, and reduced organ pathology in infected mice. It effectively decreased viral loads and inflammatory cytokines such as IL-6, IL-1β, and TNF-α in lung tissues. Enhancements in immune response were evidenced by increased CD4/CD8 ratios in the spleen. DYY also notably upregulated MAS1 protein levels and suppressed the activation of the Ras/Raf1/MEK/ERK signaling pathway. DYY enhanced respiratory function and exerted significant antiviral and immunomodulatory effects in mice infected with the HCoV-229E virus, primarily by modulating MAS1 expression and inhibiting the Ras/Raf1/MEK/ERK pathway.

摘要

病毒性肺炎的特征是由呼吸道病毒引发的肺部炎症。大元饮(DYY)是一种以治疗传染病而闻名的中药配方,据推测它在治疗病毒性肺炎方面可能具有治疗作用,尽管其具体的分子影响仍有待深入研究。本研究旨在评估大元饮在减轻小鼠感染人冠状病毒229E(HCoV - 229E)病毒所致肺炎方面的治疗效果。本研究采用HCoV - 229E病毒感染的小鼠模型,以研究大元饮对病毒诱导肺炎的治疗潜力及其潜在分子机制。评估治疗后的呼吸功能和器官指数。通过免疫组织化学评估肺组织和气管病变。使用流式细胞术分析脾脏免疫细胞组成。分别采用超敏多重电化学发光法和PCR分析对炎症细胞因子和病毒载量进行定量。通过蛋白质免疫印迹分析确定肺组织中MAS1、Ras、Raf1、MEK1/2和ERK1/2的表达水平。大元饮显著改善了感染小鼠的呼吸功能,并减轻了器官病变。它有效降低了肺组织中的病毒载量以及炎症细胞因子,如白细胞介素 - 6(IL - 6)、白细胞介素 - 1β(IL - 1β)和肿瘤坏死因子 - α(TNF - α)。脾脏中CD4/CD8比值升高证明免疫反应得到增强。大元饮还显著上调了MAS1蛋白水平,并抑制了Ras/Raf1/MEK/ERK信号通路的激活。大元饮增强了呼吸功能,并对感染HCoV - 229E病毒的小鼠发挥了显著的抗病毒和免疫调节作用,主要是通过调节MAS1表达和抑制Ras/Raf1/MEK/ERK途径实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c90b/11534925/f5f820aba304/13659_2024_474_Fig1_HTML.jpg

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