Wang Yun-Yu, Li Qian, Han Xiu-Wei, Wan Xin-Huan, Zhang Li, Niu Feng-Jv, Xin Yi-Zhou, Zhou Chang-Zheng
College of Pharmacy, Shandong University of Traditional Chinese Medicine, Ji'nan, China.
Shandong Qidu Pharmaceutical Co., Ji'nan, China.
Front Pharmacol. 2023 Aug 15;14:1164784. doi: 10.3389/fphar.2023.1164784. eCollection 2023.
Enterovirus 71 (EV71) commonly causes symptoms such as hand, foot, and mouth disease (HFMD) in infants and children and may lead to neurological disease and even death in severe cases. Appropriate vaccines for the prevention of HFMD are available in the clinic; however, they present different and serious adverse effects that cannot guarantee compliance and efficacy. The purpose of this study was to analyze the potential mechanism of Schwaegr. (BBS) against EV71 and analyze its potential active components. A previous antiviral assay was used to determine the best extraction method for the active site of BBS against EV71, and the results showed that the antiviral activity of BBS was more pronounced in the fraction that was extracted by aqueous extraction and alcoholic precipitation and then obtained by purification on a silica gel column (dichloromethane:methanol = 0:100). In addition, the therapeutic effects of BBS on EV71-infected mice were further investigated by pharmacological experiments. BBS reduced the lung index, viral titer, and degree of EV71-induced lung, brain, and skeletal muscle damage. The mechanism of anti-EV71 activity of BBS was also investigated by using ELISA and qRT-PCR, and it was found that BBS exerted its action mainly by regulating the expression of TLR3, TLR4, TNF-, IL-2, and IFN- by modulating the activation of NF-B and JAK2/STAT1 signaling pathways. Finally, the chemical structures of the active monomers in BBS were determined by using UPLC-MS and NMR techniques. The study revealed that one of the monomers on which BBS exerts its antiviral activity is saponarin. In conclusion, the results of this study suggest that BBS is considered a natural anti-EV71 product with enormous potential, and saponarin would be its non-negligible active monomer.
肠道病毒71型（EV71）通常在婴幼儿中引起手足口病（HFMD）等症状，严重时可能导致神经疾病甚至死亡。临床上有预防手足口病的合适疫苗；然而，它们存在不同且严重的不良反应，无法保证依从性和有效性。本研究的目的是分析Schwaegr.（BBS）抗EV71的潜在机制，并分析其潜在活性成分。采用先前的抗病毒试验来确定BBS抗EV71活性部位的最佳提取方法，结果表明，BBS的抗病毒活性在水提醇沉后经硅胶柱纯化（二氯甲烷：甲醇 = 0:100）得到的馏分中更为显著。此外，通过药理学实验进一步研究了BBS对EV71感染小鼠的治疗效果。BBS降低了肺指数、病毒滴度以及EV71诱导的肺、脑和骨骼肌损伤程度。还通过ELISA和qRT-PCR研究了BBS抗EV71活性的机制，发现BBS主要通过调节NF-κB和JAK2/STAT1信号通路的激活来调节TLR3、TLR4、TNF-α、IL-2和IFN-γ的表达发挥作用。最后，利用UPLC-MS和NMR技术确定了BBS中活性单体的化学结构。研究表明，BBS发挥抗病毒活性的单体之一是皂草苷。总之，本研究结果表明BBS被认为是一种具有巨大潜力的天然抗EV71产品，皂草苷将是其不可忽视的活性单体。
