Hand, foot, and mouth disease (HFMD) is caused by enterovirus 71 (EV71) in infants and children under six years of age. HFMD is characterized by fever, mouth ulcers, and vesicular rashes on the palms and feet. EV71 also causes severe neurological manifestations, such as brainstem encephalitis and aseptic meningitis. Recently, frequent outbreaks of EV71 have occurred in the Asia-Pacific region, but currently, no effective antiviral drugs have been developed to treat the disease. In this study, we investigated the antiviral effect of salvianolic acid B (SalB) on EV71. SalB is a major component of the Salvia miltiorrhiza root and has been shown to be an effective treatment for subarachnoid hemorrhages and myocardial infarctions. HeLa cells were cultured in 12-well plates and treated with SalB (100 or 10 µg/ml) and 10⁶ PFU/ml of EV71. SalB treatment (100 µg/ml) significantly decreased the cleavage of the eukaryotic eIF4G1 protein and reduced the expression of the EV71 capsid protein VP1. In addition, SalB treatment showed a dramatic decrease in viral infection, measured by immunofluorescence staining. The Akt signaling pathway, a key component of cell survival and proliferation, was significantly increased in EV71-infected HeLa cells treated with 100 µg/ml SalB. RT-PCR results showed that the mRNA for anti-apoptotic protein Bcl-2 and the cell cycle regulator Cyclin-D1 were significantly increased by SalB treatment. These results indicate that SalB activates Akt/PKB signaling and inhibits apoptosis in infected HeLa cells. Taken together, these results suggest that SalB could be used to develop a new therapeutic drug for EV71-induced HFMD.

中文翻译：

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丹酚酸 B 通过增强 AKT 信号通路抑制手足口病肠道病毒 71 的复制。

手足口病 (HFMD) 是由肠道病毒 71 (EV71) 在婴儿和 6 岁以下儿童中引起的。手足口病的特征是发烧、口腔溃疡和手掌和脚部出现水泡状皮疹。EV71 还会引起严重的神经系统表现，例如脑干脑炎和无菌性脑膜炎。近期，亚太地区EV71疫情频繁爆发，但目前尚未开发出有效的抗病毒药物来治疗该病。在这项研究中，我们研究了丹酚酸 B (SalB) 对 EV71 的抗病毒作用。SalB 是丹参的主要成分根，已被证明是治疗蛛网膜下腔出血和心肌梗塞的有效方法。HeLa 细胞在 12 孔板中培养并用 SalB（100 或 10 µg/ml）和 10 ⁶PFU/ml EV71。SalB 处理（100 µg/ml）显着降低了真核 eIF4G1 蛋白的裂解并降低了 EV71 衣壳蛋白 VP1 的表达。此外，通过免疫荧光染色测量，SalB 治疗显示病毒感染显着减少。Akt 信号通路是细胞存活和增殖的关键组成部分，在用 100 µg/ml SalB 处理的 EV71 感染的 HeLa 细胞中显着增加。RT-PCR 结果表明，抗凋亡蛋白 Bcl-2 和细胞周期调节因子 Cyclin-D1 的 mRNA 在 SalB 处理后显着增加。这些结果表明 SalB 激活 Akt/PKB 信号并抑制感染的 HeLa 细胞的细胞凋亡。总之，这些结果表明 SalB 可用于开发一种新的治疗 EV71 诱导的手足口病的药物。