title: Kaempferol regulates MAPKs and NF-κB signaling pathways to attenuate LPS-induced acute lung injury in mice.
abstract: Recent studies show that mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways are two pivotal roles contributing to the development of lipopolysaccharide (LPS)-induced acute lung injury (ALI). The present study aimed to investigate the protective effect of kaempferol (Kae), a naturally occurring flavonoid compound, on ALI and explore its possible mechanisms. Male BALB/c mice with ALI, induced by intranasal instillation of LPS, were treated or not with Kae (100 mg/kg, intragastrically) 1h prior to LPS exposure. Kae treatment attenuated pulmonary edema of mice with ALI after LPS challenge, as it markedly decreased the lung W/D ratio of lung samples, protein concentration and the amounts of inflammatory cells in BALF. Similarly, LPS mediated overproduction of proinflammatory cytokines in BALF, including TNF-α, IL-1β and IL-6, was strongly reduced by Kae. Histological studies demonstrated that Kae substantially inhibited LPS-induced alveolar wall thickness, alveolar hemorrhage and leukocytes infiltration in lung tissue with evidence of reduced myeloperoxidase (MPO) activity. Kae also efficiently increased superoxide dismutase (SOD) activity of lung sample when compared with LPS group, which was obviously reduced by LPS administration. In addition, Western blot analysis indicated that the activation of MAPKs and NF-κB signaling pathways stimulated by LPS was significantly blocked by Kae. Taken together, our results suggest that Kae exhibits a protective effect on LPS-induced ALI via suppression of MAPKs and NF-κB signaling pathways, which may involve the inhibition of tissue oxidative injury and pulmonary inflammatory process.
authors: College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, People's Republic of China.
authors: Xiaojun
authors: X
authors: Chen
authors: Xiaofeng
authors: X
authors: Yang
authors: Tianjiao
authors: T
authors: Liu
authors: Mingfeng
authors: M
authors: Guan
authors: Xiangru
authors: X
authors: Feng
authors: Wei
authors: W
authors: Dong
authors: Xiao
authors: X
authors: Chu
authors: Jing
authors: J
authors: Liu
authors: Xiuli
authors: X
authors: Tian
authors: Xinxin
authors: X
authors: Ci
authors: Hongyu
authors: H
authors: Li
authors: Jingyuan
authors: J
authors: Wei
authors: Yanhong
authors: Y
authors: Deng
authors: Xuming
authors: X
authors: Deng
authors: Gefu
authors: G
authors: Chi
authors: Zhiliang
authors: Z
authors: Sun
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D044949:Kaempferols / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D044949:Kaempferols; D008070:Lipopolysaccharides; D016328:NF-kappa B; C006552:kaempferol; D009195:Peroxidase