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.

中文翻译：

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从虎杖中分离的大黄素对柯萨奇病毒 B4 抑制作用的体外和体内研究

柯萨奇病毒 B4 (CVB4) 感染缺乏有效的治疗方法强调了寻找新型抗病毒化合物的重要性。大黄素（1,3,8-trihydroxy-6-methylanthraquinone）是从虎杖根和根茎中提取的天然蒽醌衍生物之一。在本研究中，在体外和小鼠中探索了使用大黄素作为潜在抗病毒药物治疗 CVB4 感染的可能性。大黄素以浓度和时间依赖性方式减少 Hep-2 细胞上的 CVB4 进入和复制，50% 有效浓度 (EC50) 为 12.06 μM，选择性指数 (SI) 分别为 5.08。实时定量 PCR (qPCR) 测定进一步证实了大黄素对 CVB4 进入和复制的抑制作用。结果进一步表明，口服不同剂量大黄素的小鼠，存活率、体重和平均死亡时间（MTD）均呈剂量依赖性增加，同时心肌病毒滴度和病理评分/病变显着降低。此外，大黄素可以在体外和体内抑制 CVB4 诱导的细胞凋亡。我们的结果表明，大黄素可作为潜在的抗病毒药物用于 CVB4 感染的暴露后预防。