Screening of Antiviral Components of Ma Huang Tang and Investigation on the Ephedra Alkaloids Efficacy on Influenza Virus Type A

Abstract

Although Ma Huang Tang (MHT) has long been considered as a classical formula for respiratory infections like influenza, bronchitis and asthma, its chemical ingredients that really exert the main 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) and D-pseudo- ephedrine (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 the TLR3, TLR4 and TLR7 signaling pathways, which were 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 an 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 and 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 pathways. The overall findings demonstrate that, as effective and inexpensive natural substances, Ephedra alkaloids and MHT may have potential utility in clinical management.

Exploring active ingredients and function mechanisms of Ephedra-bitter almond for prevention and treatment of Corona virus disease 2019 (COVID-19) based on network pharmacology

“…And luteolin was also resistant to dengue virus, influenza A virus, Japanese encephalitis virus, and so on [ 50 – 52 ]. In addition, ephedrine alkaloids, such as ephedrine, pseudoephedrine, and methylephedrine, had potential therapeutic effects on viral-induced respiratory infections [ 53 ]. This indicated that ephedra-bitter almond may resist COVID-19 through antiviral and sympathomimetic effects.…”

Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice

“…Toll-like receptor 4 (TLR4), the first identified member of TLR family, is a transmembrane protein characterized by an extracellular domain containing leucine-rich repeats (LRRs) with which the MD-2 molecule is associated [52]. After activated by virus, the TIR domain of TLR4 interacts with the TIR domain of MyD88 and binds to another TIR-containing adaptor protein, MyD88 adaptor-like (MAL), leading to an inflammatory cascade effector enzyme such as the expression of TNF-α, IL-1β, and IL-6 [53][54][55][56]. Thus, when B4 bound to TLR4, it will prevent the virus from activating TLR4, which may be an alternative strategy to treat FM1-induced viral pneumonia.…”

Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice

“…Toll-like receptor 4 (TLR4), the rst identi ed member of TLR family, is a transmembrane protein characterized by an extracellular domain containing leucine-rich repeats (LRRs) with which the MD-2 molecule is associated [53]. After activated by virus, the TIR domain of TLR4 interacts with the TIR domain of MyD88 and binds to another TIR-containing adaptor protein, MyD88 adaptor-like (MAL), leading to an in ammatory cascade effector enzyme such as the expression of TNF-α, IL-1β, and IL-6 [54][55][56][57]. Thus, when B4 bound to TLR4, it will prevent the virus from activating TLR4, which may be an alternative strategy to treat FM1-induced viral pneumonia.…”