Ephedra, an ancient herb, is applied to treat common cold and influenza for such a long time in China. Pseudoephedrine is a main active ingredient from Ephedra which is used for relieving nasal congestion clinically. We previously reported that pseudoephedrine showed a potent anti-inflammatory effect other than sympathomimetic effects. In the present study, we aimed to investigate whether pseudoephedrine could protect mice from the H1N1 virus infection. The mice were infected with a 20% LD50 influenza A virus (IAV) suspension via intranasal administration to establish a virus infection model. Further, the mice were orally administered pseudoephedrine or oseltamivir for 4 days from one day after infection. Our results showed that pseudoephedrine improved lung pathological damage during the IVA infection period, and it dramatically increased the survival rate and attenuated loss of body weight compared with the virus-infected control group. In addition, pseudoephedrine inhibited the cytokine storms and mRNAs expression of the TLR7 signaling pathway. Surprisingly, pseudoephedrine showed an inhibitory effect on the replication of IAV. These results give clear evidence that pseudoephedrine is a potential anti-influenza drug by blunting cytokine storms and inhibition of replication of IAV, and following these results, we speculate that it should be tested in the novel coronavirus pneumonia (COVID-19, a severe epidemic in China currently) in which the cytokine storms play a key role to damage bronchi and lung in the early stage.
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