title: Protective Role of Liriodendrin in Sepsis-Induced Acute Lung Injury.
abstract: In current study, we investigated the role of liriodendrin, a constituent isolated from Sargentodoxa cuneata (Oliv.) Rehd. Et Wils (Sargentodoxaceae), in cecal ligation and puncture (CLP)-induced acute lung inflammatory response and injury (ALI). The inflammatory mediator levels in bronchoalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay (ELISA). Pathologic changes in lung tissues were evaluated via pathological section with hematoxylin and eosin (H&E) staining. To investigate the mechanism whereby liriodendrin regulates lung inflammation, the phosphorylation of the NF-kB (p65) and expression of vascular endothelial growth factor (VEGF) were determined by western blot assay. We show that liriodendrin treatment significantly improved the survival rate of mice with CLP-induced sepsis. Pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration were markedly decreased by liriodendrin. In addition, liriodendrin decreased the production of the proinflammatory mediators including (TNF-α, IL-1β, MCP-1, and IL-6) in lung tissues. Vascular permeability and lung myeloperoxidase (MPO) accumulation in the liriodendrin-treated mice were substantially reduced. Moreover, liriodendrin treatment significantly suppressed the expression of VEGF and activation of NF-kB in the lung. We further show that liriodendrin significantly reduced the production of proinflammatory mediators and downregulated NF-kB signaling in LPS-stimulated RAW 264.7 macrophage cells. Moreover, liriodendrin prevented the generation of reactive oxygen species (ROS) by upregulating the expression of SIRT1 in RAW 264.7 cells. These findings provide a novel theoretical basis for the possible application of liriodendrin in clinic.
authors: Tianjin Nankai Hospital, Tianjin, 300100, China.
authors: Lei
authors: L
authors: Yang
authors: Tianjin Nankai Hospital, Tianjin, 300100, China.
authors: Dihua
authors: D
authors: Li
authors: Tianjin Nankai Hospital, Tianjin, 300100, China.
authors: Yuzhen
authors: Y
authors: Zhuo
authors: Tianjin Nankai Hospital, Tianjin, 300100, China.
authors: Shukun
authors: S
authors: Zhang
authors: Tianjin Nankai Hospital, Tianjin, 300100, China.|Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors: Ximo
authors: X
authors: Wang
authors: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. hgao@zeus.bwh.harvard.edu.
authors: Hongwei
authors: H
authors: Gao
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D005663:Furans / Q000494:pharmacology* / Q000627:therapeutic use; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration; D011014:Pneumonia; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000473:pathology*; D056564:Sirtuin 1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D005663:Furans; D005960:Glucosides; D018836:Inflammation Mediators; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C068512:liriodendrin; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: ALI; NF-kB; VEGF; liriodendrin; sepsis