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Protective Role of Liriodendrin in Sepsis-Induced Acute Lung Injury

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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.

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Acknowledgments

The authors thank the National Natural Science Foundation of China (No. 81470263) for their great support in financing these researches.

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Authors and Affiliations

  1. Tianjin Nankai Hospital, Tianjin, 300100, China

    Lei Yang, Dihua Li, Yuzhen Zhuo, Shukun Zhang & Ximo Wang

  2. 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

    Ximo Wang & Hongwei Gao

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  1. Lei Yang
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Correspondence to Hongwei Gao.

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Yang, L., Li, D., Zhuo, Y. et al. Protective Role of Liriodendrin in Sepsis-Induced Acute Lung Injury. Inflammation 39, 1805–1813 (2016). https://doi.org/10.1007/s10753-016-0416-1

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