1. Picroside II attenuates hyperhomocysteinemia-induced endothelial injury by reducing inflammation, oxidative stress and cell apoptosis.
- Author
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Wang Y, Hong Y, Zhang C, Shen Y, Pan YS, Chen RZ, Zhang Q, and Chen YH
- Subjects
- Animals, Antioxidants metabolism, Cell Line, Endothelium metabolism, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells metabolism, Humans, Hyperhomocysteinemia metabolism, Inflammation metabolism, Mice, Mice, Inbred C57BL, NF-kappa B metabolism, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Sirtuin 1 metabolism, Up-Regulation drug effects, Apoptosis drug effects, Cinnamates pharmacology, Endothelium drug effects, Hyperhomocysteinemia drug therapy, Inflammation drug therapy, Iridoid Glucosides pharmacology, Oxidative Stress drug effects
- Abstract
Picroside II (P-II), one of the main active components of scrophularia extract, which have anti-oxidative, anti-inflammatory effects, but its effect on hyperhomocysteinemia (HHcy) induced endothelial injury remains to be determined. Here, we test whether P-II protects HHcy-induced endothelial dysfunction against oxidative stress, inflammation and cell apoptosis. In vitro study using HUVECs, and in hyperhomocysteinemia mouse models, we found that HHcy decreased endothelial SIRT1 expression and increased LOX-1 expression, subsequently causing reactive oxygen species generation, up-regulation of NADPH oxidase activity and NF-κB activation, thereby promoting pro-inflammatory response and cell apoptosis. Blockade of Sirt1 with Ex527 or siRNASIRT1 increased LOX-1 expression, whereas overexpression of SIRT1 decreased LOX-1 expression markedly. P-II treatment significantly increased SIRT1 expression and reduced LOX-1 expression, and protected against endothelial cells from Hcy-induced oxidative injury, inflammation and apoptosis. However, blockade of SIRT1 or overexpression of LOX-1 attenuated the therapeutic effects of P-II. In conclusion, our results suggest that P-II prevents the Hcy induced endothelial damage probably through regulating the SIRT1/LOX-1 signaling pathway., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Published
- 2019
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