title: Phloretin attenuates LPS-induced acute lung injury in mice via modulation of the NF-κB and MAPK pathways.
abstract: Phloretin, which can be isolated from apple trees, has demonstrable anti-inflammatory and anti-oxidant effects in macrophages. We previously reported that phloretin could inhibit the inflammatory response and reduce intercellular adhesion molecule 1 (ICAM-1) expression in interleukin (IL)-1β-activated human lung epithelial cells. In the present study we now evaluate whether phloretin exposure could ameliorate lipopolysaccharide (LPS)-induced acute lung injury in mice. Intra-peritoneal injections of phloretin were administered to mice for 7 consecutive days, prior to the induction of lung injury by intra-tracheal administration of LPS. Our subsequent analyses demonstrated that phloretin could significantly suppress LPS-induced neutrophil infiltration of lung tissue, and reduce the levels of IL-6 and tumor necrosis factor (TNF)-α in serum and bronchoalveolar lavage fluid. We also found that phloretin modulated myeloperoxidase activity and superoxide dismutase activity, with decreased gene expression levels for chemokines, proinflammatory cytokines, and ICAM-1 in inflamed lung tissue. Phloretin also significantly reduced the phosphorylation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), thus limiting the inflammatory response, while promoting expression of heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2, both of which are cytoprotective. Our findings suggest that, mechanistically, phloretin attenuates the inflammatory and oxidative stress pathways that accompany lung injury in mice via blockade of the NF-κB and MAPK pathways.
authors: Graduate Institute of Health Industry Technology and Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan; Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan City 33303, Taiwan.
authors: Wen-Chung
authors: WC
authors: Huang
authors: Department of Nursing, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan.
authors: Ching-Long
authors: CL
authors: Lai
authors: Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan.
authors: Yuan-Ting
authors: YT
authors: Liang
authors: Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan.
authors: Hui-Chih
authors: HC
authors: Hung
authors: Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan.
authors: Hui-Chia
authors: HC
authors: Liu
authors: Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan City 33303, Taiwan; Department of Nursing, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan. Electronic address: ccliu@mail.cgust.edu.tw.
authors: Chian-Jiun
authors: CJ
authors: Liou
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D010693:Phloretin / Q000494:pharmacology / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D008565:Membrane Proteins; D016328:NF-kappa B; D009195:Peroxidase; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D013482:Superoxide Dismutase; D020928:Mitogen-Activated Protein Kinases; D010693:Phloretin
keywords: Acute lung injury; Cytokine; Lipopolysaccharide; NF-κB; Phloretin