Abstract
This study aimed to investigate the effects of paeoniflorin, the main active ingredient of the medicinal plant Paeonia lactiflora Pall., on the permeability of endothelial cells induced by lipopolysaccharide (LPS) and the underlying mechanisms. Human umbilical vein endothelial cells (HUVECs) were stimulated by LPS. Extravasated FITC-dextran reflecting permeability was assessed by multimode microplate reader, and the migration of bis-carboxyethyl-carboxyfluorescein acetoxy-methyl-labeled human acute monocytic leukemia cell line and leukemia cell line cells through HUVECs were analyzed by fluorescence microscopy. The phosphorylations of phosphatidylinositol 3-kinase (PI3K)/Akt, protein kinase C (PKC), and cofilin in HUVECs were assessed by western blotting, and the F-actin level was detected by laser scanning confocal microscopy. After LPS stimulation, inflammatory endothelial cells exhibited significantly increased permeability. Paeoniflorin (10, 30, and 100 μM) inhibited dextran extravasation and leukocyte migration through HUVECs induced by LPS in a concentration-dependent manner. Moreover, paeoniflorin was able to suppress the phosphorylations of PI3K/Akt, PKC, and cofilin, as well as F-actin reorganization in HUVECs induced by LPS. These findings revealed that paeoniflorin partly blocked LPS-induced endothelium permeability, supporting a new explanation for its anti-inflammatory effects.
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This work was funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions and Program for Changjiang Scholars and Innovative Research Team in University (IRT1193).
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Huan Xu and Jie Song equally contributed to this paper.
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Xu, H., Song, J., Gao, X. et al. Paeoniflorin Attenuates Lipopolysaccharide-Induced Permeability of Endothelial Cells: Involvements of F-Actin Expression and Phosphorylations of PI3K/Akt and PKC. Inflammation 36, 216–225 (2013). https://doi.org/10.1007/s10753-012-9537-3
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DOI: https://doi.org/10.1007/s10753-012-9537-3