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肺炎清化汤通过抑制 NF-κB 和 p38 MAPK 通路抑制巨噬细胞和中性粒细胞浸润发挥抗流感作用。

Fei-yan-qing-hua decoction exerts an anti-inflammatory role during influenza by inhibiting the infiltration of macrophages and neutrophils through NF-κB and p38 MAPK pathways.

机构信息

The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

出版信息

J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118846. doi: 10.1016/j.jep.2024.118846. Epub 2024 Sep 19.

DOI:10.1016/j.jep.2024.118846
PMID:39306208
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Fei-Yan-Qing-Hua decoction (FYQHD) is an empirical formula that has shown clinical success in treating community-acquired pneumonia (CAP) for two decades. Influenza viral infection is a significant trigger for severe pneumonia, yet the role of FYQHD in treating influenza remains unclear.

AIM OF THE STUDY

This study aimed to assess the potential efficacy of FYQHD in treating influenza viral infection and to elucidate its underlying mechanisms.

MATERIALS AND METHODS

The protective effects of FYQHD against influenza were evaluated through survival assessments and pathological analyses. Transcriptomic analysis was performed to identify the genes and pathways influenced by FYQHD in influenza. The anti-inflammatory effects and molecular mechanisms of FYQHD were studied in macrophages stimulated by Toll-like receptor (TLR) 7 ligation in vitro. The key constituents of FYQHD absorbed in mouse sera were identified using untargeted metabolomics, and the anti-inflammatory activity of some of these compounds in macrophages was evaluated using ELISA.

RESULTS

Our findings demonstrate that FYQHD enhances survival and reduces lung damage in PR8-infected mice, primarily through its anti-inflammatory properties. Lung indexes and organ damage were significantly lower in the PR8 + OSV + FYQHD group compared to the PR8 + OSV group, indicating a potential complementary therapeutic effect of FYQHD and OSV in treating influenza. FYQHD effectively reduced chemokine expression, thereby decreasing the chemotaxis and infiltration of inflammatory monocytes/macrophages and neutrophils in the lungs. The anti-inflammatory effects of FYQHD in macrophages were achieved through the inhibition of NF-κB activation and p38 phosphorylation. The key constituents of FYQHD absorbed in mouse sera were identified, with some, such as wogonin, luteolin, kaempferol, and isorhamnetin, showing anti-inflammatory effects in primary macrophages.

CONCLUSION

FYQHD demonstrates protective efficacy against influenza and shows promise as an adjuvant therapeutic agent, particularly when used in combination with antiviral drugs like OSV. The potent anti-inflammatory components within FYQHD provide a basis for further exploration in drug research and development aimed at combating influenza.

摘要

民族药理学相关性

肺炎清化汤(FYQHD)是一种经验方,在治疗社区获得性肺炎(CAP)方面已有 20 年的临床成功经验。流感病毒感染是导致严重肺炎的一个重要诱因,但 FYQHD 在治疗流感方面的作用尚不清楚。

研究目的

本研究旨在评估 FYQHD 治疗流感病毒感染的潜在疗效,并阐明其潜在机制。

材料和方法

通过生存评估和病理分析评价 FYQHD 对流感的保护作用。采用转录组学分析方法鉴定 FYQHD 对流感影响的基因和途径。在体外通过 Toll 样受体(TLR)7 交联刺激巨噬细胞,研究 FYQHD 的抗炎作用及其分子机制。采用非靶向代谢组学方法鉴定 FYQHD 在小鼠血清中吸收的关键成分,并采用 ELISA 方法评估其中一些化合物在巨噬细胞中的抗炎活性。

结果

本研究发现 FYQHD 可提高感染 PR8 病毒的小鼠的存活率并减轻肺部损伤,主要通过其抗炎作用。与 PR8+OSV 组相比,PR8+OSV+FYQHD 组的肺指数和器官损伤明显降低,提示 FYQHD 和 OSV 联合治疗流感可能具有互补的治疗效果。FYQHD 能有效降低趋化因子的表达,从而减少炎症性单核细胞/巨噬细胞和中性粒细胞在肺部的趋化和浸润。FYQHD 在巨噬细胞中的抗炎作用是通过抑制 NF-κB 激活和 p38 磷酸化实现的。鉴定出 FYQHD 在小鼠血清中吸收的关键成分,其中一些成分,如黄苓素、木犀草素、山奈酚和异鼠李素,在原代巨噬细胞中具有抗炎作用。

结论

FYQHD 对流感具有保护作用,有望成为一种辅助治疗药物,特别是与 OSV 等抗病毒药物联合使用时。FYQHD 中具有强大抗炎作用的成分可为进一步研究开发抗流感药物提供依据。

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