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

IF 4.8 3区 化学 Q1 CHEMISTRY, MEDICINAL Natural Products and Bioprospecting Pub Date : 2024-11-04 DOI:10.1007/s13659-024-00474-8
Rui Li, Wen Zhang, Bei Huang, Guotong Sun, Yifei Xie, Junke Song, Shumei Wang, Guanhua Du
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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.

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大活络银可缓解 HCoV-229E 诱导的肺炎症状并调节 Ras/Raf1/MEK/ERK 通路。
病毒性肺炎是由呼吸道病毒引发的肺部炎症。大活络银(DYY)是一种以治疗感染性疾病而闻名的传统中药配方,被认为对治疗病毒性肺炎有一定疗效,但其具体的分子影响仍未得到充分研究。本研究旨在评估 DYY 对减轻 HCoV-229E 病毒诱导的小鼠肺炎的治疗效果。本研究采用HCoV-229E病毒感染的小鼠模型,研究DYY对病毒诱导的肺炎的治疗潜力和潜在的分子机制。对治疗后的呼吸功能和器官指标进行了评估。通过免疫组化对肺组织和气管病变进行评估。使用流式细胞术分析了脾脏免疫细胞的组成。炎症细胞因子和病毒载量分别采用高敏多重电化学发光法和 PCR 分析法进行量化。通过 Western 印迹分析确定了肺组织中 MAS1、Ras、Raf1、MEK1/2 和 ERK1/2 的表达水平。DYY能明显改善感染小鼠的呼吸功能,减少器官病理变化。它能有效减少肺组织中的病毒载量和炎性细胞因子,如 IL-6、IL-1β 和 TNF-α。脾脏中 CD4/CD8 比率的增加证明了免疫反应的增强。DYY 还能显著上调 MAS1 蛋白水平,抑制 Ras/Raf1/MEK/ERK 信号通路的激活。DYY 主要通过调节 MAS1 的表达和抑制 Ras/Raf1/MEK/ERK 通路,增强了感染 HCoV-229E 病毒的小鼠的呼吸功能,并发挥了显著的抗病毒和免疫调节作用。
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来源期刊
Natural Products and Bioprospecting
Natural Products and Bioprospecting CHEMISTRY, MEDICINAL-
CiteScore
8.30
自引率
2.10%
发文量
39
审稿时长
13 weeks
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