AUTHOR=Wang Yun-Yu , Li Qian , Han Xiu-Wei , Wan Xin-Huan , Zhang Li , Niu Feng-Jv , Xin Yi-Zhou , Zhou Chang-Zheng 

TITLE=Bryum billardieri Schwaegr. against EV71 infection: in vitro and in vivo antiviral effects, identification of molecular mechanisms and active monomers

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1164784

DOI=10.3389/fphar.2023.1164784

ISSN=1663-9812

ABSTRACT=Enterovirus 71 (EV71) commonly causes symptoms such as hand, foot and mouth disease (HFMD) in infants and children, and in severe cases may lead to neurological disease and even death. There are appropriate vaccines for the prevention of HFMD already 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 Bryum billardieri Schwaegr. (BBS) against EV71 and to analyze its potential active components. The previous in vitro 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 which was extracted by aqueous extraction and alcoholic precipitation, and then obtained by purification on silica gel column (dichloromethane: methanol = 0:100). In addition, the therapeutic effects of BBS on EV71-infected mice were further investigated by in vivo pharmacological experiments. BBS reduced the lung index, viral titer, and the 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-α, IL-2 and IFN-γ by modulating the activation of NF-κB and JAK2/STAT1 signaling pathways. Finally, the chemical structures of the active monomers in BBS were finally determined using UPLC-MS and NMR techniques. The study revealed that one of the monomers in which BBS exerts antiviral activity is saponarin. In conclusion, the results of this study suggest that BBS is considered as a natural anti-EV71 product with enormous potential, and saponarin would be its non-negligible active monomer.