Abstract
In the present study, we aimed to investigate the effects of puerarin on the hyperpermeability of vascular endothelial cells induced by lipopolysaccharide (LPS) and its underlying mechanisms. Human umbilical vein endothelial cells (HUVECs) were pre-incubated with puerarin (25, 50, and 100 μM) for 1 h, and then exposed to LPS (1 μg/mL). The monolayer permeability of endothelial cells was assessed by measuring the paracellular flux of FITC-dextran 40,000 (FD40). The expression of vascular endothelial cadherin (VE-cadherin) in HUVECs was examined by Western blotting analysis. A total of 18 mice were randomly assigned into three groups as follows: control group, LPS group, and puerarin group. The pulmonary W/D ratio (wet-to-dry weight ratios) was calculated, and the lung morphology was examined. The levels of TNF-α and IL-1β in cell supernatant and mouse serum were determined by ELISA. Compared with the control group, LPS obviously increased the flux of FD40 and the monolayer permeability, raised the levels of TNF-α and IL-1β in cell supernatant, and reduced the VE-cadherin expression in HUVECs. However, puerarin (25, 50, and 100 μM) was able to relieve such LPS-induced increase in flux of FD40 and then reduce the hyperpermeability. Puerarin decreased the levels of TNF-α and IL-1β in cell supernatant and increased the VE-cadherin expression in HUVECs (P < 0.05). Moreover, LPS obviously increased the levels of TNF-α and IL-1β in mouse serum and elevated the pulmonary W/D ratios, resulting in lung injury. However, all of above-mentioned LPS-induced changes were improved by puerarin pre-treatment. Puerarin could alleviate LPS-induced hyperpermeability in endothelial cells via preventing downregulation of endothelial cadherin.
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Funding
The study was supported by Health Commission Foundation of Hunan Province (grant no. B2017043), Hunan College Students Research Learning and Innovative Experiment Program (grant no. [2017]205-722), and the Scientific Research Fund of Hunan Provincial Education Department (grant no. 18C1014).
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Deng, Hf., Wang, S., Wang, Xl. et al. Puerarin Protects Against LPS-Induced Vascular Endothelial Cell Hyperpermeability via Preventing Downregulation of Endothelial Cadherin. Inflammation 42, 1504–1510 (2019). https://doi.org/10.1007/s10753-019-01014-0
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DOI: https://doi.org/10.1007/s10753-019-01014-0