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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00961

Screening of antiviral components of Ma Huang Tang and investigation on the antiviral mechanisms of Ephedra alkaloids

Wen y. Wei1, Chong y. Shao1,  Zhou H. Fen1, Yi y. Lu1,  Li Yu1, Hai x. Du1, Hai t. Wan1 and  Yu He1*
  • 1Zhejiang Chinese Medical University, China

Although Ma Huang Tang (MHT) has long been considered as a classical formula for respiratory infections like influenza, bronchitis and asthma, its chemical ingredients really exert the antiviral efficacy are still obscure. In this study we aimed to screen its antiviral components and investigate the potential mechanisms. The MDCK cellular research results showed that, among nine predominant ingredients of MHT, L-methylephedrin (LMEP), L-ephedrine (LEP), D-pseudoephedrine (DPEP) significantly inhibited the proliferation of influenza A virus in vitro, and the inhibitory effect at 24 h after the treatment was more obvious than that at 48 h. They also significantly inhibited the mRNA expression levels of related genes in TLR3, TLR4 and TLR7 signaling pathways, which accompanied with the down-regulation of TNF-α level and the up-regulation of IFN-β level in the cell supernatant. Therefore, three Ephedra alkaloids exert antiviral effect in vitro which may be closely related to the inhibition of viral replication and the modulation of inflammatory response. Animal research further indicated, at the 3rd and 7th days after infection, LEP and DPEP significantly attenuated lung injury, decreased lung index, virus load in the lung and the level of IL-1β in serum, inhibited the mRNA expression levels of TNF-α, TLR3, TLR4, TLR7, MyD88, NF-κB p65 and RIG-1 as well as the protein expression levels of TLR4, TLR7, MyD88 and NF-κB p65, markedly increased thymus index, the level of IL-10 in serum and the mRNA expression level of IFN-γ. LEP and DPEP have certain protective effects on the influenza virus-infected mice, which may be associated with their abilities of effectively alleviating lung injury, improving the immunologic function of infected mice and adjusting the host's TLRs and RIG-1 pathway. The overall findings demonstrate that, as the effective and inexpensive natural substances, Ephedra alkaloids and MHT may have potential utility in the clinical management.

Keywords: ephedra alkaloids, Influenza A virus, virus load, Inflammation response, TLRs signal pathway

Received: 21 Feb 2019; Accepted: 29 Jul 2019.

Edited by:

Enzo Tramontano, University of Cagliari, Italy

Reviewed by:

Haolong Liu, Peking University Health Science Centre, China
Angela Corona, University of Cagliari, Italy
Suryaprakash Sambhara, Centers for Disease Control and Prevention (CDC), United States  

Copyright: © 2019 Wei, Shao, Fen, Lu, Yu, Du, Wan and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Yu He, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang Province, China, heyu0923@hotmail.com