Abstract
BackgroundInfluenza virus is a single-stranded RNA virus that causes influenza in humans and animals. About 600 million people around the world suffer from influenza every year. Upon recognizing viral RNA molecules, TLR7 (Toll-like receptor) initiates corresponding immune responses. Traditional Chinese Medicines (TCMs), including Yinqiao powder, Xinjiaxiangruyin and Guizhi-and-Mahuang decoction, have been extensively applied in clinical treatment of influenza. Although the therapeutic efficacy of TCMs against influenza virus in vivo was reported previously, its underlying mechanisms are not clearly understood. This study aimed to investigate the immunological mechanisms in the treatment of influenza virus infected mice with three Chinese herbal compounds as well as the effect on TLR7/NF-κB signaling pathway during recovery.MethodsWild type and TLR7 KO C57BL/6 mice were infected with influenza virus FM1 and then treated with three TCMs. The physical parameters of mice (body weight and lung index) and the expression levels of components in TLR7/NF-κB signaling pathway were evaluated.ResultsAfter viral infection, Guizhi-and-Mahuang decoction and Yinqiao powder showed better anti-viral effect under normal condition. Compared to the viral control group, expression levels of TLR7, MyD88, IRAK4 and NF-κB were significantly reduced in all treatment groups. Furthermore, the three TCM treatment groups showed poor therapeutic efficacy and no difference in viral load compared to the viral control group in TLR7 KO mice.ConclusionOur study indicated that Guizhi-and-Mahuang decoction and Yinqiao powder might play a crucial role of anti-influenza virus by regulating TLR7/NF-κB signal pathway.
Highlights
Influenza virus is a single-stranded RNA virus that causes influenza in humans and animals
The average body weight of mice on day 6 in virus control group, Xinjiaxiangruyin group and Yinqiao powder group were decreased to 72.08%, 75.16% (NS) and 79.94% (P < 0.05) of the original body weight, respectively, while mice in Oseltamivir group and Guizhi-and-Mahuang decoction group were better with 93.29% (P < 0.01) and 84.45% (P < 0.01) of the original body weight, respectively
We further demonstrated that virus infection increased protein expression levels of Toll-like receptor 7 (TLR7), myeloid differentiation primary response 88 (MyD88), interleukin-1 receptor-associated kinase 4 (IRAK4) and NF-κB with western blotting, while Oseltamivir, Guizhiand-Mahuang decoction, Yinqiao powder decreased their expression
Summary
Influenza virus is a single-stranded RNA virus that causes influenza in humans and animals. This study aimed to investigate the immunological mechanisms in the treatment of influenza virus infected mice with three Chinese herbal compounds as well as the effect on TLR7/NF-κB signaling pathway during recovery. Two NAIs, oseltamivir and zanamivir, are FDA approved for use against type A and type B influenza infections [6]. During the 2007–08 influenza season, emergence and transmission of oseltamivir-resistant type A (H1N1) viruses, with an H274Y mutation in the neuraminidase, were observed in several countries in the Northern Hemisphere and spread globally [7]. Researchers have identified oseltamivir resistant influenza type A (H5N1) and type B viruses [5], which makes it urgent for the research and development of new and effective antiinfluenza drugs
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