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提取物在小鼠心肌炎模型中抑制柯萨奇病毒B3诱导的心肌炎。

Extract Inhibit Coxsackievirus-B3 Induced Myocarditis in Murine Myocarditis Model.

作者信息

Lee Yun-Gyeong, Park Jung-Ho, Jeon Eun-Seok, Kim Jin-Hee, Lim Byung-Kwan

机构信息

Department of Biomedical Science, Jungwon University, Goesan 28024, Republic of Korea.

Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheonju 28116, Republic of Korea.

出版信息

J Microbiol Biotechnol. 2016 Nov 28;26(11):2012-2018. doi: 10.4014/jmb.1605.05056.

Abstract

Coxsackievirus B3 (CVB3) is the main cause of acute myocarditis and dilated cardiomyopathy. Plant extracts are considered as useful materials to develop new antiviral drugs. We had previously selected candidate plant extracts, which showed anti-inflammatory effects. We examined the antiviral effects by using a HeLa cell survival assay. Among these extracts, we chose the () extract, which showed strong antiviral effect and preserved cell survival in CVB3 infection. We investigated the mechanisms underlying the ability of extract to inhibit CVB3 infection and replication. HeLa cells were infected by CVB3 with or without extract. Erk and Akt activities, and their correlation with virus replication were observed. Live virus titers in cell supernatants and viral positive- and negative-strand RNA amplification were measured. extract significantly increased HeLa cell survival in different concentrations (100-10 µg/ml). CVB3 capsid protein VP1 expression (76%) and viral protease 2A-induced eIF4G1 cleavage (70%) were significantly decreased in extract (100 µg/ml) treated cells. The levels of positive- (20%) and negative-strand (80%) RNA were dramatically decreased compared with the control, as revealed by reverse transcription-PCR. In addition, extract improved mice survival (51% vs 26%) and dramatically reduced heart inflammation in a CVB3-induced myocarditis mouse model. These results suggested that extract significantly inhibited replication and myocarditis damage. may be developed as a therapeutic drug for .

摘要

柯萨奇病毒B3(CVB3)是急性心肌炎和扩张型心肌病的主要病因。植物提取物被认为是开发新型抗病毒药物的有用材料。我们之前筛选出了具有抗炎作用的候选植物提取物。我们通过HeLa细胞存活试验检测了其抗病毒效果。在这些提取物中,我们选择了()提取物,其在CVB3感染中表现出强大的抗病毒作用并能维持细胞存活。我们研究了该提取物抑制CVB3感染和复制能力的潜在机制。HeLa细胞在有或没有该提取物的情况下感染CVB3。观察了Erk和Akt的活性及其与病毒复制的相关性。测量了细胞上清液中的活病毒滴度以及病毒正链和负链RNA的扩增情况。该提取物在不同浓度(100 - 10μg/ml)下均显著提高了HeLa细胞的存活率。在经该提取物(100μg/ml)处理的细胞中,CVB3衣壳蛋白VP1的表达(降低了76%)和病毒蛋白酶2A诱导的eIF4G1裂解(降低了70%)均显著下降。逆转录聚合酶链反应显示,与对照组相比,正链RNA(降低了20%)和负链RNA(降低了80%)的水平显著降低。此外,在CVB3诱导的心肌炎小鼠模型中,该提取物提高了小鼠的存活率(51%对26%)并显著减轻了心脏炎症。这些结果表明,该提取物显著抑制了CVB3的复制和心肌炎损伤。该提取物可能被开发为治疗CVB3的药物。

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