Inhibitory Activity of Honeysuckle Extracts against Influenza A VirusIn VitroandIn Vivo
Inhibitory Activity of Honeysuckle Extracts against Influenza A VirusIn VitroandIn Vivo
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金银花提取物对甲型流感病毒的体外和体内抑制活性
DOI：
10.1007/s12250-020-00302-6
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发表时间：
2020-10-12
影响因子：
5.5
通讯作者：
Guo, Min
中科院分区：
文献类型：
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作者：
Li, Mengwei;Wang, Yuxu;Guo, Min
在中国，蜂蜜用于治疗流感病毒感染已有数千年的历史。然而，其主要活性成分和作用机制仍有待阐明。本研究制备了金银花酸提物、黄酮类提取物、总提物和酸黄酮混合物4种提取物，以明确金银花抗病毒活性的主要成分。细胞病变抑制试验表明，四种提取物均能抑制流感病毒H1N1、H3 N2和奥司他韦耐药突变株H1N1-H275 Y的复制。体外实验表明，该化合物对H1N1、H3 N2和H1N1-H275 Y的EC 50分别为3.8、4.1和20 μg/mL，与奥司他韦和利巴韦林具有竞争性抗病毒活性。蜂蜜酸提取物也显示出最显著的体内抗病毒活性。以600 mg/kg/d的剂量口服给予酸提取物有效地减轻了病毒性肺炎，维持了体重，并将感染致死剂量H1N1的小鼠的存活率提高到30%。加药时间实验和神经氨酸酶（NA）抑制实验结果表明，金银花提取物对流感病毒NA具有广谱抑制作用。黄酮类提取物对H7N9流感病毒NA的抑制作用最强，IC 50为24.7 μg/mL。这些结果表明，这些提取物可能通过抑制流感病毒的释放来发挥其抗病毒活性。总之，我们的研究结果表明，金银花的酸类和黄酮类提取物是主要的抗病毒活性成分，酸类提取物具有开发成为抗流感病毒，特别是对奥司他韦耐药病毒的抗病毒剂的潜力。
Honeysuckle has been used in the treatment of influenza virus infection for thousands of years in China. However, its main active components and the functional mechanisms remain to be elucidated. Here, four honeysuckle extracts, including acids extract, flavonoids extract, total extract and acids-flavonoids mixture, were prepared to clarify the main active antiviral components. The cytopathic effect reduction assay showed that all the four extracts inhibited the replication of influenza viruses H1N1, H3N2 and the oseltamivir-resistant mutant strain H1N1-H275Y. The acids-flavonoids mixture had the strongest inhibitory effects in vitro with EC50 values of 3.8, 4.1, and > 20 μg/mL against H1N1, H3N2 and H1N1-H275Y, respectively, showing competitive antiviral activity with oseltamivir and ribavirin. Honeysuckle acids extract also showed the most significant antiviral activity in vivo. Oral administration of the acids extract at a dosage of 600 mg/kg/d effectively alleviated viral pneumonia, maintained body weight and improved the survival rate to 30% of the mice infected with a lethal dose of H1N1. The results of time-of-drug addition experiment and neuraminidase (NA) inhibition assay showed that honeysuckle extracts had a broad-spectrum inhibitory effect against influenza virus NAs. The flavonoid extract showed the strongest inhibitory effect on the NA of influenza virus H7N9 with an IC50 of 24.7 μg/mL. These results suggested that these extracts might exert their antiviral activity by suppressing the release of influenza viruses. Briefly, our findings demonstrate that acids and flavonoids extracts of honeysuckle are the major antiviral active components, and the acids extract has the potential to be developed into an antiviral agent against influenza virus, especially for oseltamivir-resistant viruses.