Kaempferol ameliorates H9N2 swine influenza virus-induced acute lung injury by inactivation of TLR4/MyD88-mediated NF-κB and MAPK signaling pathways

• Published in: Biomedicine & pharmacotherapy 2017-05, Vol.89, p.660-672
• Main Authors: Zhang, Ruihua, Ai, Xia, Duan, Yongjie, Xue, Man, He, Wenxiao, Wang, Cunlian, Xu, Tong, Xu, Mingju, Liu, Baojian, Li, Chunhong, Wang, Zhijun, Zhang, Ruihong, Wang, Guohua, Tian, Shufei, Liu, Huifeng
• Format: Article
• Language: English
• Subjects: Acute lung injury; Acute Lung Injury - drug therapy; Acute Lung Injury - etiology; Acute Lung Injury - pathology; Animals; Antiviral Agents - pharmacology; Capillary Permeability - drug effects; Cell Line; Cytokines - antagonists & inhibitors; Humans; Influenza A Virus, H9N2 Subtype - drug effects; Influenza, Human - drug therapy; Influenza, Human - pathology; Influenza, Human - virology; Internal Medicine; Kaempferol; Kaempferols - pharmacology; Lung - pathology; Male; MAPKs; Medical Education; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases - drug effects; Myeloid Differentiation Factor 88 - biosynthesis; Myeloid Differentiation Factor 88 - drug effects; Myeloid Differentiation Factor 88 - genetics; Nuclear factor-kappaB; Signal Transduction - drug effects; Toll-like receptor 4; Toll-Like Receptor 4 - biosynthesis; Toll-Like Receptor 4 - drug effects; Toll-Like Receptor 4 - genetics; Transcription Factor RelA - drug effects
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.02.081

Abstract Kaempferol, a very common type of dietary flavonoids, has been found to exert antioxidative and anti-inflammatory properties. The purpose of our investigation was designed to reveal the effect of kaempferol on H9N2 influenza virus-induced inflammation in vivo and in vitro. In vivo, BALB/C mice were infected intranasally with H9N2 influenza virus with or without kaempferol treatment to induce acute lung injury (ALI) model. In vitro, MH-S cells were infected with H9N2 influenza virus with or without kaempferol treatment. In vivo, kaempferol treatment attenuated pulmonary edema, the W/D mass ratio, pulmonary capillary permeability, myeloperoxidase (MPO) activity, and the numbers of inflammatory cells. Kaempferol reduced ROS and Malondialdehyde (MDA) production, and increased the superoxide dismutase (SOD) activity. Kaempferol also reduced overproduction of TNF-α, IL-1β and IL-6. In addition, kaempferol decreased the H9N2 viral titre. In vitro, ROS, MDA, TNF-α, IL-1β and IL-6 was also reduced by kaempferol. Moreover, our data showed that kaempferol significantly inhibited the upregulation of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phosphorylation level of IκBα and nuclear factor-κB (NF-κB) p65, NF-κB p65 DNA binding activity, and phosphorylation level of MAPKs, both in vivo and in vitro. These results suggest that kaempferol exhibits a protective effect on H9N2 virus-induced inflammation via suppression of TLR4/MyD88-mediated NF-κB and MAPKs pathways, and kaempferol may be considered as an effective drug for the potential treatment of influenza virus-induced ALI.