Paeoniflorin Attenuates Lipopolysaccharide-Induced Permeability of Endothelial Cells: Involvements of F-Actin Expression
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Paeoniflorin Attenuates Lipopolysaccharide-Induced Permeability of Endothelial Cells: Involvements of F-Actin Expression and Phosphorylations of PI3K/Akt and PKC Huan Xu,1 Jie Song,2 Xinghua Gao,1 Zhao Xu,1 Xianxiang Xu,1 Yufeng Xia,3,4 and Yue Dai1,4
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. KEY WORDS: paeoniflorin; endothelium; permeability; PKC; cofilin.
Paeoniflorin, a monoterpene glycoside isolated from the roots, has been identified as the main active ingredient responsible for the biological activities [1]. Our previous work showed that the anti-inflammatory action of paeoniflorin was related to the prevention of adhesion between inflammatory endothelial cells and leukocytes by downregulating the expression of adhesion molecules [2]. The candidacy of paeoniflorin as an anti-inflammatory agent prompts better understanding of the downstream pathways responsible for paeoniflorin-associated anti-inflammatory activity. Under physiological conditions, endothelial cells interconnect to form a selective semipermeable membrane that serves as a barrier between blood and tissue and is responsible for the exchange of fluid and macromolecules on both sides of the vessel wall. Inflammatory stimulation results in damage and dysfunction of the endothelial cell junction, leading to increased vascular permeability, plasma macromolecules, leukocyte infiltration, and even edema or inflammatory injury. Endothe-
INTRODUCTION The dry roots of Paeonia lactiflora Pall. have long been used in oriental medicine for analgesia and nourishment of the blood and liver. Accumulative data show that P. lactiflora roots possess multiple physiological benefits, including immunoregulation, improvement of learning and memor
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