Abstract
Lasting activations of toll-like receptors (TLRs), MAPK and NF-κB pathways can support influenza A virus (IAV) infection and promote pneumonia. In this study, we have investigated the effect and mechanism of action of emodin on IAV infection using qRT-PCR, western blotting, ELISA, Nrf2 luciferase reporter, siRNA and plaque inhibition assays. The results showed that emodin could significantly inhibit IAV (ST169, H1N1) replication, reduce IAV-induced expressions of TLR2/3/4/7, MyD88 and TRAF6, decrease IAV-induced phosphorylations of p38/JNK MAPK and nuclear translocation of NF-κB p65. Emodin also activated the Nrf2 pathway, decreased ROS levels, increased GSH levelss and GSH/GSSG ratio, and upregulated the activities of SOD, GR, CAT and GSH-Px after IAV infection. Suppression of Nrf2 via siRNA markedly blocked the inhibitory effects of emodin on IAV-induced activations of TLR4, p38/JNK, and NF-κB pathways and on IAV-induced production of IL-1β, IL-6 and expression of IAV M2 protein. Emodin also dramatically increased the survival rate of mice, reduced lung edema, pulmonary viral titer and inflammatory cytokines, and improved lung histopathological changes. In conclusion, emodin can inhibit IAV replication and influenza viral pneumonia, at least in part, by activating Nrf2 signaling and inhibiting IAV-induced activations of the TLR4, p38/JNK MAPK and NF-κB pathways.
Highlights
Influenza A virus (IAV) is a major respiratory pathogen that can mutate or reassort to generate a new strain and is annually responsible for high morbidity, mortality and huge economic loss all over the world
We have examined the anti-influenza A virus (IAV) activity of emodin and explored and explored itsofmechanism of action
TCM materials are the result of countless clinical practices during the past several thousands of years
Summary
Influenza A virus (IAV) is a major respiratory pathogen that can mutate or reassort to generate a new strain and is annually responsible for high morbidity, mortality and huge economic loss all over the world. IAV infection can activate toll-like receptor (TLR) signaling pathways. Oxidative stress plays an important role in replication and IAV-mediated pneumonia. Oxidative stress plays an important role in IAV replication and IAV-mediated pneumonia[15]. ROS-mediated pathway can inhibit the activation of TLR pathways [17], and can reduce LPS-stimulated cell surface transport of TLR4 and sequentially downstream cascades, including. ROS-mediated cell surface transport of TLR4 and suppresses sequentiallythe suppresses the downstream cascades, MyD88/TRIF pIkB/IRF3, and provides protection against sepsis [18]. Et Zucc., has been reported to possess antioxidant, anti-inflammatory, immunosuppressive, antiviraland andanti-tumor anti-tumor activities [19,20]. Emodin can inhibit infections infections of coxsackievirus (CV), human respiratory syncytial (RSV), epstein-barr virus (EBV).
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