Protective Role of Liriodendrin in Sepsis-Induced Acute Lung Injury
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ORIGINAL ARTICLE
Protective Role of Liriodendrin in Sepsis-Induced Acute Lung Injury Lei Yang,1 Dihua Li,1 Yuzhen Zhuo,1 Shukun Zhang,1 Ximo Wang,1,2 and Hongwei Gao2,3
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. KEY WORDS: liriodendrin; sepsis; ALI; VEGF; NF-kB.
INTRODUCTION Sepsis is a disseminated inflammatory response elicited by microbial infection [1] and is the major cause of mortality in critically ill patients [2]. Approximately 30 % of sepsis patients progress to multi-organ dysfunction syn1
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 3 To whom correspondence should be addressed at 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. E-mail: [email protected] 2
drome (MODS) with 18 % developing acute lung injury (ALI). Despite significant advances in intense care research and diverse therapeutic trials made in the past few decades, ALI remains a severe clinical problem and still presents a high mortality rate of approximately 40 % [3, 4]. The pathophys
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