Anti-inflammatory effects of theaflavin-3?-gallate during influenza virus infection through regulating the TLR4/MAPK/p38 pathway
文献类型： 外文期刊
第一作者： Sima, Mingwei
作者： Sima, Mingwei;Deng, Xiuwen;Yue, Donghui;Gao, Yuwei;Sima, Mingwei;Lv, Chaoxiang;Qi, Jing;Guo, Jin;Luo, Rongbo;Deng, Xiuwen;Li, Yuanguo;Wang, Tiecheng;Gao, Yuwei;Qi, Jing;Guo, Jin;Yue, Donghui;Gao, Yuwei
作者机构：
关键词： Theaflavin derivatives; Influenza a virus; TLR4; MAPK; p38 signaling pathway; Anti-inflammatory
期刊名称：EUROPEAN JOURNAL OF PHARMACOLOGY （ 影响因子：5.195； 五年影响因子：4.721 ）
ISSN： 0014-2999
年卷期： 2023 年 938 卷
页码：
收录情况： SCI
摘要： Severe pathological damage caused by the influenza virus is one of the leading causes of death. However, the prevention and control strategies for influenza virus infection have certain limitations, and the exploration for new influenza antiviral drugs has become the major research direction. This study evaluated the antiviral ac-tivities of four theaflavin derivatives (TFs). Cytopathic effect (CPE) reduction assay revealed that theaflavin-3 '- gallate (TF2b) and theaflavin (TF1) could effectively inhibit the replication of influenza viruses H1N1-UI182, H1N1-PR8, H3N2, and H5N1, and TF2b exhibited the most significant antiviral activity in vivo. Intraperito-neal injection of TF2b at 40 mg/kg/d effectively alleviated viral pneumonia, maintained body weight, and improved the survival rate of mice infected with a lethal dose of H1N1-UI182 to 55.56%. Hematological analysis of peripheral blood further showed that TF2b increased the number of lymphocytes and decreased the number of neutrophils, monocytes, and platelets in the blood of infected mice. RT-qPCR results showed that TF2b reduced the mRNA expression levels of inflammatory cytokines (IL-6, TNF-alpha, and IL-113), chemokines (CXCL-2 and CCL-3), and interferons (IFN-alpha and IFN-gamma) after influenza virus infection. In addition, TF2b significantly down-regulated the expression levels of TLR4, p-p38, p-ERK, and cytokines IL-6, TNF-alpha, IL-113, and IL-10. These results suggest that TF2b not only significantly inhibits viral replication and proliferation in vitro, but also alleviates pneumonia injury in vivo. Its antiviral effect might be attributed to the down-regulation of influenza virus-induced inflam-matory cytokines by regulating the TLR4/MAPK/p38 signaling pathway.
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