Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou, 225009, China.
Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225009, China.
J Ethnopharmacol. 2021 Jul 15;275:114063. doi: 10.1016/j.jep.2021.114063. Epub 2021 Apr 1.
Fufang-Yinhua-Jiedu Granules (FFYH) optimized from a Yin-Qiao-San, as traditional Chinese medicine (TCM), was used to treat influenza and upper respiratory tract infection and was recommended for the prevention and treatment of SARS in 2003 and current COVID-19 in Anhui Province in 2020.
In the clinical studies, FFYH was very effective for the treatment of influenza, but the mechanism of action against influenza A virus remains unclear. In the present study, we investigated the antiviral effect of FFYH against influenza A virus in vitro and vivo. Moreover, the potential mechanism of FFYH against influenza A virus in vivo was investigated for the first time.
CPE inhibition assay and HA assay were used to evaluate the in vitro antiviral effects of FFYH against influenza A virus H1N1, H3N2, H5N1, H7N9 and H9N2. Mice were used to evaluate the antiviral effect of FFYH in vivo with ribavirin and lianhuaqingwen as positive controls. RT-PCR was used to quantify the mRNA transcription of TNF-α, IL-6, IFN-γ, IP10, and IL-1β mRNA. ELISA was used to examine the expression of inflammatory factors such as TNF-α, IL-6, IFN-γ, IP10, and IL-1β in sera. The blood parameters were analyzed with auto hematology analyzer. Moreover, the potential mechanism of FFYH against influenza A virus in vivo was also investigated.
FFYH showed a broad-spectrum of antiviral activity against H1N1, H3N2, H5N1, H7N9, and H9N2 influenza A viruses. Furthermore, FFYH dose-dependently increased the survival rate, significantly prolonged the median survival time of mice, and markedly reduced lung injury caused by influenza A virus. Also, FFYH significantly improve the sick signs, food taken, weight loss, blood parameters, lung index, and lung pathological changes. Moreover, FFYH could markedly inhibit the inflammatory cytokine expression of TNF-α, IL-6, IFN-γ, IP10, IL-10, and IL-1β mRNA or protein via inhibition of the TLR7/MyD88/NF-κB signaling pathway in vivo.
FFYH not only showed a broad-spectrum of anti-influenza virus activity in vitro, but also exhibited a significant protective effect against lethal influenza virus infection in vivo. Furthermore, our results indicated that the in vivo antiviral effect of FFYH against influenza virus may be attributed to suppressing the expression of inflammatory cytokines via regulating the TLR7/MyD88/NF-κB signaling pathway. These findings provide evidence for the clinical treatment of influenza A virus infection with FFYH.
复方金银花解毒颗粒（FFYH）是由银翘散优化而来的一种中药，用于治疗流感和上呼吸道感染，并在 2003 年推荐用于 SARS 的预防和治疗，以及 2020 年在安徽省用于 COVID-19 的预防和治疗。
在临床研究中，FFYH 对流感的治疗非常有效，但抗流感 A 病毒的作用机制仍不清楚。在本研究中，我们研究了 FFYH 对甲型流感病毒的体外和体内抗病毒作用。此外，首次研究了 FFYH 对体内甲型流感病毒的潜在作用机制。
采用 CPE 抑制试验和 HA 试验评价 FFYH 对甲型流感病毒 H1N1、H3N2、H5N1、H7N9 和 H9N2 的体外抗病毒作用。以利巴韦林和连花清瘟为阳性对照，用小鼠评价 FFYH 的体内抗病毒作用。采用 RT-PCR 定量检测 TNF-α、IL-6、IFN-γ、IP10 和 IL-1βmRNA 的转录。采用 ELISA 检测血清中 TNF-α、IL-6、IFN-γ、IP10 和 IL-1β 等炎症因子的表达。采用自动血液分析仪分析血液参数。此外，还研究了 FFYH 对体内甲型流感病毒的潜在作用机制。
FFYH 对 H1N1、H3N2、H5N1、H7N9 和 H9N2 甲型流感病毒均具有广谱抗病毒活性。此外，FFYH 呈剂量依赖性地提高了存活率，显著延长了感染小鼠的中位生存时间，并显著减轻了流感病毒引起的肺损伤。此外，FFYH 可显著改善感染流感病毒的小鼠的临床症状、摄食量、体重减轻、血液参数、肺指数和肺组织病理学变化。此外，FFYH 可通过抑制 TLR7/MyD88/NF-κB 信号通路，显著抑制 TNF-α、IL-6、IFN-γ、IP10、IL-1βmRNA 或蛋白的表达。
FFYH 不仅在体外表现出广谱抗流感病毒活性，而且在体内对致死性流感病毒感染具有显著的保护作用。此外，我们的结果表明，FFYH 对流感病毒的体内抗病毒作用可能归因于通过调节 TLR7/MyD88/NF-κB 信号通路抑制炎症细胞因子的表达。这些发现为 FFYH 临床治疗流感病毒感染提供了证据。
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