Liu Tianrun, Li Yingyu, Wang Lumeng, Zhang Xiaomeng, Zhang Yuxuan, Gai Xuejie, Chen Li, Liu Lei, Yang Limin, Wang Baixin
School of Medicine, Jiamusi University, Jiamusi, China.
The Affiliated First Hospital, Jiamusi University, Jiamusi, China.
Front Pharmacol. 2023 Sep 19;14:1260288. doi: 10.3389/fphar.2023.1260288. eCollection 2023.
Mulberry leaf (ML) is known for its antibacterial and anti-inflammatory properties, historically documented in "Shen Nong's Materia Medica". This study aimed to investigate the effects of ML on enterovirus 71 (EV71) using network pharmacology, molecular docking, and experiments. We successfully pinpointed shared targets between mulberry leaves (ML) and the EV71 virus by leveraging online databases. Our investigation delved into the interaction among these identified targets, leading to the identification of pivotal components within ML that possess potent anti-EV71 properties. The ability of these components to bind to the targets was verified by molecular docking. Moreover, bioinformatics predictions were used to identify the signaling pathways involved. Finally, the mechanism behind its anti-EV71 action was confirmed through experiments. Our investigation uncovered 25 active components in ML that targeted 231 specific genes. Of these genes, 29 correlated with the targets of EV71. Quercetin, a major ingredient in ML, was associated with 25 of these genes. According to the molecular docking results, Quercetin has a high binding affinity to the targets of ML and EV71. According to the KEGG pathway analysis, the antiviral effect of Quercetin against EV71 was found to be closely related to the NF-κB signaling pathway. The results of immunofluorescence and Western blotting showed that Quercetin significantly reduced the expression levels of VP1, TNF-α, and IL-1β in EV71-infected human rhabdomyosarcoma cells. The phosphorylation level of NF-κB p65 was reduced, and the activation of NF-κB signaling pathway was suppressed by Quercetin. Furthermore, our results showed that Quercetin downregulated the expression of JNK, ERK, and p38 and their phosphorylation levels due to EV71 infection. With these findings in mind, we can conclude that inhibiting the NF-κB signaling pathway is a critical mechanism through which Quercetin exerts its anti-EV71 effectiveness.
桑叶（ML）以其抗菌和抗炎特性而闻名，历史记载于《神农本草经》。本研究旨在通过网络药理学、分子对接和实验研究桑叶对肠道病毒71型（EV71）的影响。我们通过利用在线数据库成功确定了桑叶（ML）和EV71病毒之间的共同靶点。我们的研究深入探讨了这些已确定靶点之间的相互作用，从而确定了桑叶中具有强大抗EV71特性的关键成分。通过分子对接验证了这些成分与靶点的结合能力。此外，利用生物信息学预测来确定涉及的信号通路。最后，通过实验证实了其抗EV71作用的机制。我们的研究发现桑叶中有25种活性成分靶向231个特定基因。在这些基因中，有29个与EV71的靶点相关。槲皮素是桑叶中的主要成分，与其中25个基因相关。根据分子对接结果，槲皮素对桑叶和EV71的靶点具有高结合亲和力。根据KEGG通路分析，发现槲皮素对EV71的抗病毒作用与NF-κB信号通路密切相关。免疫荧光和蛋白质免疫印迹结果表明，槲皮素显著降低了EV71感染的人横纹肌肉瘤细胞中VP1、TNF-α和IL-1β的表达水平。NF-κB p65的磷酸化水平降低，槲皮素抑制了NF-κB信号通路的激活。此外，我们的结果表明，槲皮素下调了由于EV71感染导致的JNK、ERK和p38的表达及其磷酸化水平。基于这些发现，我们可以得出结论，抑制NF-κB信号通路是槲皮素发挥其抗EV71效力的关键机制。
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