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BMC Complementary Medicine and Therapies

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01-12-2020 | Influenza Virus | Research article

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

Authors: Jiashun Li, Xiang Jie, Xiaoli Liang, Ziyu Chen, Peifang Xie, Xiping Pan, Beixian Zhou, Jing Li

Published in: BMC Complementary Medicine and Therapies | Issue 1/2020

Abstract

Background

Human respiratory system infected with influenza A virus (IAV) elicited a robust pro-inflammatory response that resulted in severe illness and even death. Currently, limited immunomodulator is available to counteract IAV-associated pneumonia in the clinic. Sinensetin, a polymethoxylated flavone with five methoxy groups, has been found to possess anti-agiogenesis, anti-inflammatory and anti-diabetic activities. However, the effects of sinensetin on IAV-triggered pro-inflammatory response remain unclear. In the present study, the anti-inflammatory effects and corresponding possible mechanism of sinensetin in IAV-infected A549 cells were subjected to investigations.

Methods

The cytotoxic effects of sinensetin towards A549 cells was detected by MTT and LDH assays. The antiviral activity of sinensetin against influenza A virus was assayed in A549 cells with an engineered replication-competent influenza A virus carrying Gaussia luciferase reporter gene infection. The effect of sinensetin on influenza A virus-triggered inflammatory reaction was determined by qRT-PCR, Luminex assays, ELISA and Western blot.

Results

Our results showed that sinensetin did not exhibit antiviral activity against A/PR/8/34 (H1N1). Meanwhile, sinensetin treatment significantly decreased IAV-induced expression of pro-inflammatory mediators at mRNA and protein levels, including IL-6, TNF-α, IP-10, IL-8 and MCP-1. Additionally, levels of cyclooxygenase (COX)-2 and the downstream product prostaglandin E₂ (PGE₂) up-regulated by IAV infection were dramatically suppressed by sinensetin. The mechanistic investigation revealed that sinensetin treatment suppressed the NF-κB transcriptional activity using the NF-κB reporter stable HEK293 cell line stimulated with TNF-α (20 ng/mL) or influenza H1N1 virus. Furthermore, sinensetin abrogated influenza H1N1 virus-induced activation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings.

Conclusion

Collectively, our results indicated that sinensetin has potential capacity to attenuate IAV-triggered pro-inflammatory response via inactivation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings, which implied that sinensetin may be a promising candidate drug for influenza H1N1 virus infection therapeutics.

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Title: Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings
Authors: Jiashun Li
Xiang Jie
Xiaoli Liang
Ziyu Chen
Peifang Xie
Xiping Pan
Beixian Zhou
Jing Li
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Influenza Virus
Influenza
Published in: BMC Complementary Medicine and Therapies / Issue 1/2020
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-020-02918-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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