Ann Transl Med . Isorhamnetin inhibits amplification of influenza A H1N1 virus inflammation mediated by interferon via the RIG-I/JNK pathway

[tetano]

Ann Transl Med


. 2021 Aug;9(16):1327.
doi: 10.21037/atm-21-3532.
Isorhamnetin inhibits amplification of influenza A H1N1 virus inflammation mediated by interferon via the RIG-I/JNK pathway


Jing Li ^{1 2} , Yifan Xu ^{1 2} , Zhiwei Lin ¹ , Lili Guan ¹ , Shuqi Chen ^{2 3} , Luqian Zhou ¹



Affiliations

• PMID: 34532464
• PMCID: PMC8422108
• DOI: 10.21037/atm-21-3532

Free PMC article

Abstract

Background: Interferon (IFN) amplifies the influenza virus-mediated inflammatory response by forming a paracrine signal feedback loop, which is considered an important cause of excessive inflammatory damage. Isorhamnetin has a wide spectrum of beneficial pharmacological properties, including anti-inflammatory and antiviral effects. The regulatory effect and mechanism of isorhamnetin on influenza virus-mediated inflammation have not yet been reported.
Methods: We pre-treated A549 cells with IFN-β (50 ng/mL) for 4 h followed by IAV (H1N1) infection to simulate the inflammation amplification effect caused by the paracrine effect of IFN-β. The anti-inflammation activity of isorhamnetin against amplification inflammation of interferon mediated by IAV (H1N1) was assessed by performing quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay (ELISA) in A549 cells.
Results: Compared with the virus infection group, the IFN-β pretreatment virus infection group had an upregulated level of pro-inflammatory cytokine expression, which was inhibited by isorhamnetin significantly via the retinoic acid-induced gene I (RIG-I)/c-Jun N-terminal kinase (JNK) signaling pathway. Molecular docking studies further verified that isorhamnetin can interact with JNK.
Conclusions: Our work was the first to demonstrate the anti-inflammatory activity and mechanism of isorhamnetin during influenza virus infection. Isorhamnetin significantly improves the excessive inflammatory response mediated by IAV (H1N1) infection mainly via the RIG-I/JNK pathway. Additionally, isorhamnetin exhibited an apparent antiviral effect of H1N1 in vitro.

Keywords: Isorhamnetin; inflammation; influenza A virus (IAV); type I interferon.