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从虎杖中分离得到的大黄素对柯萨奇病毒 B₄ 的体外和体内抑制作用研究。

In vitro and in vivo studies of the inhibitory effects of emodin isolated from Polygonum cuspidatum on Coxsakievirus B₄.

机构信息

State Key Laboratory of Virology, Institute of Medical Virology, School of Medicine, Wuhan 430071, China.

出版信息

Molecules. 2013 Sep 25;18(10):11842-58. doi: 10.3390/molecules181011842.

Abstract

The lack of effective therapeutics for Coxsackievirus B₄ (CVB₄) infection underscores the importance of finding novel antiviral compounds. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is one of the natural anthraquinone derivatives obtained from the root and rhizome of Polygonum cuspidatum. In the present study, the possibility of using emodin as a potential antiviral to treat CVB₄ infection was explored in vitro and in mice. Emodin reduced CVB₄ entry and replication on Hep-2 cells in a concentration- and time-dependent manner, with a 50% effective concentration (EC₅₀) of 12.06 μM and selectivity index (SI) of 5.08, respectively. The inhibitory effect of emodin for CVB₄ entry and replication was further confirmed by a quantitative real time PCR (qPCR) assay. The results further showed that the mice orally treated with different dosages of emodin displayed a dose dependent increase of survival rate, body weight and prolonged mean time of death (MTD), accompanied by significantly decreased myocardial virus titers and pathologic scores/lesions. Moreover, emodin could inhibit CVB₄-induced apoptosis in vitro and in vivo. Our results indicated that emodin could be used as potential antiviral in the post-exposure prophylaxis for CVB₄ infection.

摘要

柯萨奇病毒 B4(CVB4)感染缺乏有效的治疗方法,这凸显了寻找新型抗病毒化合物的重要性。大黄素(1,3,8-三羟基-6-甲基蒽醌)是从虎杖的根和根茎中提取的天然蒽醌衍生物之一。在本研究中,探讨了大黄素作为一种潜在的抗病毒药物治疗 CVB4 感染的可能性,包括在体外和体内实验中进行研究。大黄素以浓度和时间依赖的方式降低 Hep-2 细胞中 CVB4 的进入和复制,其 50%有效浓度(EC50)为 12.06 μM,选择性指数(SI)为 5.08。定量实时 PCR(qPCR)检测进一步证实了大黄素对 CVB4 进入和复制的抑制作用。结果还表明,经不同剂量大黄素口服处理的小鼠的存活率、体重呈剂量依赖性增加,且平均死亡时间(MTD)延长,同时心肌病毒滴度和病理评分/病变明显降低。此外,大黄素可抑制 CVB4 诱导的细胞凋亡,无论是在体外还是体内实验中。我们的研究结果表明,大黄素可作为 CVB4 感染后的暴露后预防的潜在抗病毒药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fe1/6269740/7a34ba009d2c/molecules-18-11842-g001.jpg

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