Li Yuting, Zou Haimei, Ma Lin, Hu Dingwen, Long Haishan, Lin Jingnan, Luo Ziqing, Zhou Ye, Liao Feng, Wang Xianyang, Meng Yu, Wang Wenbiao, Li Geng, Zhang Zhongde
Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
J Ethnopharmacol. 2025 Feb 11;341:119314. doi: 10.1016/j.jep.2024.119314. Epub 2024 Dec 31.
Severe influenza, marked by excessive cytokine production, is a major contributor to death in hospitalized individuals. Fuzheng Jiedu decoction (FZJDD), an effective traditional Chinese herbal recipe, has demonstrated promising results in combating the COVID-19 pandemic by reducing mortality and improving Symptoms, and has exhibited anti-inflammatory properties in both clinical trials and laboratory research. Given that pneumonia is a common outcome of SARS-CoV-2 and H1N1 virus infections, we hypothesized that FZJDD may also have therapeutic effects on influenza-related pneumonia and acute lung injury (ALI).
This research sought to explore the impact and underlying mechanisms of FZJDD on ALI caused by the H1N1 virus in mice.
FZJDD was characterized using UHPLC-MS/MS. A mouse model infected with H1N1 virus was used to examine the therapeutic and protective benefits of FZJDD in a living organism, by monitoring body weight fluctuations, lung index, histopathological changes, lung injury scores, and survival rates. Lung tissues underwent haematoxylin-eosin staining, western blotting, qRT-PCR and plaque reduction assay. Blood serum was gathered to assess levels of IL-1β, IL-6, TNF-α through ELISA testing. The impact of FZJDD on the NLRP3 inflammasome was further evaluated in macrophages.
FZJDD treatment significantly mitigated weight loss, reduced lung index, alleviated histopathological injury, and improved the survival rates in mice with H1N1 virus-induced ALI, demonstrating a protective effect against influenza virus infection. qRT-PCR and Western blot assays revealed that FZJDD treatment ameliorated the hyperinflammatory response caused by the H1N1 virus in lung tissue by suppressing NLRP3 inflammasome activation, without impacting viral replication. In vitro experiments additionally verified that FZJDD treatment can suppress the activation of the NLRP3 inflammasome triggered by the H1N1 virus.
Our findings demonstrate that FZJDD treatment can mitigate ALI caused by H1N1 virus and enhance the survival rate in mice, while it doesn't lower viral titers in the lungs. FZJDD achieves these outcomes by curbing excessive inflammation and blocking the activation of NLRP3 inflammasome.
严重流感以细胞因子过度产生为特征，是住院患者死亡的主要原因。扶正解毒汤（FZJDD）是一种有效的中药方剂，在抗击新冠疫情中通过降低死亡率和改善症状取得了有前景的成果，并且在临床试验和实验室研究中均表现出抗炎特性。鉴于肺炎是SARS-CoV-2和H1N1病毒感染的常见结果，我们推测FZJDD可能对流感相关肺炎和急性肺损伤（ALI）也有治疗作用。
本研究旨在探讨FZJDD对小鼠H1N1病毒所致ALI的影响及潜在机制。
采用超高效液相色谱-串联质谱法（UHPLC-MS/MS）对FZJDD进行表征。利用感染H1N1病毒的小鼠模型，通过监测体重波动、肺指数、组织病理学变化、肺损伤评分和存活率，来检验FZJDD在活体中的治疗和保护作用。对肺组织进行苏木精-伊红染色、蛋白质印迹法、定量逆转录聚合酶链反应（qRT-PCR）和蚀斑减少试验。采集血清，通过酶联免疫吸附测定（ELISA）检测白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平。在巨噬细胞中进一步评估FZJDD对NLRP3炎性小体的影响。
FZJDD治疗显著减轻了H1N1病毒诱导的ALI小鼠的体重减轻，降低了肺指数，减轻了组织病理学损伤，提高了存活率，显示出对流感病毒感染的保护作用。qRT-PCR和蛋白质印迹分析表明，FZJDD治疗通过抑制NLRP3炎性小体激活，改善了肺组织中H1N1病毒引起的过度炎症反应，而不影响病毒复制。体外实验进一步证实，FZJDD治疗可抑制H1N1病毒触发的NLRP3炎性小体激活。
我们的研究结果表明，FZJDD治疗可减轻H1N1病毒所致ALI并提高小鼠存活率，同时不降低肺内病毒滴度。FZJDD通过抑制过度炎症反应和阻断NLRP3炎性小体激活实现这些结果。
