title: Kaempferol ameliorates H9N2 swine influenza virus-induced acute lung injury by inactivation of TLR4/MyD88-mediated NF-κB and MAPK signaling pathways.
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.
authors.affiliation: Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, Animal Science College, HeBei North University, Zhangjiakou 075131, China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ai
authors.affiliation: Army Artillery Training Base, Xuanhua 075100, China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Duan
authors.affiliation: The Eighth Hospital of Shijiazhuang, Shijiazhuang 050000, China.
authors.forename: Man
authors.initials: M
authors.lastname: Xue
authors.affiliation: Army Artillery Training Base, Xuanhua 075100, China.
authors.forename: Wenxiao
authors.initials: W
authors.lastname: He
authors.affiliation: Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, Animal Science College, HeBei North University, Zhangjiakou 075131, China.
authors.forename: Cunlian
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, Animal Science College, HeBei North University, Zhangjiakou 075131, China. Electronic address: xutong1969@sohu.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Xu
authors.affiliation: Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, Animal Science College, HeBei North University, Zhangjiakou 075131, China.
authors.forename: Mingju
authors.initials: M
authors.lastname: Xu
authors.affiliation: Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, Animal Science College, HeBei North University, Zhangjiakou 075131, China.
authors.forename: Baojian
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, Animal Science College, HeBei North University, Zhangjiakou 075131, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Li
authors.affiliation: Army Artillery Training Base, Xuanhua 075100, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Huang Yang Cheng Central School, ChaYouZhongQi, Wulanchabu City, Inner Mongolia 013550, China.
authors.forename: Ruihong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, Animal Science College, HeBei North University, Zhangjiakou 075131, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, Animal Science College, HeBei North University, Zhangjiakou 075131, China.
authors.forename: Shufei
authors.initials: S
authors.lastname: Tian
authors.affiliation: Qianjin Farm of Jiansanjiang Administration of Heilongjiang Province, Heilongjiang 156331, PR China.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Liu
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors; D006801:Humans; D053127:Influenza A Virus, H9N2 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D044949:Kaempferols / Q000494:pharmacology*; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D051996:Transcription Factor RelA / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D044949:Kaempferols; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; C006552:kaempferol; D020928:Mitogen-Activated Protein Kinases
keywords: Acute lung injury; Kaempferol; MAPKs; Nuclear factor-kappaB; Toll-like receptor 4