2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐d‐glucoside protects human umbilical vein endothelial cells against lysophosphatidylcholine‐induced apoptosis by upregulating superoxide dismutase and glutathione peroxidase

Abstract

2,3,5,4 0 -Tetrahydroxystilbene-2-O-b-D-glucoside (TSG) has been shown to protect human umbilical vein endothelial cells (HUVECs) from lysophosphatidylcholine (LPC)-induced injury; however, the underlying molecular mechanism remains to be determined. The aim of this study was to investigate the protective mechanism of TSG against LPC-induced injury in HUVECs. We established a stable LPC-induced cell model by treating HUVECs with various concentrations of LPC and found 10.0 mg/mL of LPC to be optimal for inducing HUVECs injury. The effects of TSG on LPC-induced cell injury were assessed by cell counting kit-8, apoptosis assay, transmission electron microscope, and measurement of malondialdehyde (MDA), the antioxidant enzymes superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase, and mitochondrial membrane potential. The mRNA and protein levels of caspase-3, Bax, Bcl-2, PARP-1, and cytochrome C were assayed by real-time reverse transcriptasepolymerase chain reaction and immunoblotting, respectively. TSG pretreatment was able to prevent LPC-induced HUVECs injury and restore cell viability in a concentration-dependent manner. LPC treated cells showed typical apoptotic morphological changes including cytoplasmic vacuolation, swollen mitochondria, and characteristic biochemical hallmarks of apoptosis including loss of mitochondrial membrane potential, activation of caspase-3, decrease of Bcl-2, increase of PARP-1, upregulation of Bax, and release of cytochrome C, all of which were apparently inhibited by TSG pretreatment. Treatment of HUVECs with LPC led to decrease of SOD and glutathione peroxidase in addition to rapid increase of MDA and ROS levels. Pretreatment with TSG restored SOD and glutathione peroxidase levels to that of normal levels, and significantly decreased ROS and MDA levels. Our data indicate that TSG inhibits apoptosis of HUVECs mediated by LPC through blocking the mitochondrial apoptotic pathway and suggest that the mechanisms underlying the protective effects of TSG are related to the activation of SOD and glutathione peroxidase, the clearance of intracellular ROS, and reduction of lipid peroxidation.

Tetrahydroxystilbene Glycoside Improves Microvascular Endothelial Dysfunction and Ameliorates Obesity-Associated Hypertension in Obese ZDF Rats Via Inhibition of Endothelial Autophagy

“…TSG is a free radical-scavenger [22], and exerts anti-aging effects in mammals via a neural insulin/IGF-1 signaling pathway [19]. TSG exhibits strong anti-oxidative and anti-inflammatory effects, as well as protecting mammals from cerebral ischemia and/or reperfusion injury [23, 43]. The ability for TSG to induce proliferation of cardiac stem cells as well as the transcription and differentiation of cardiomyocyte genes has been validated.…”

“…TSG has been reported to help people live longer [18], protect impaired neural networks [19], improve blood flow [20], attenuate inflammatory responses [21], prevent the production of oxygen radicals and protect against oxidized LDL-induced endothelial dysfunction [22]. Previously, we demonstrated that TSG inhibits lysophosphatidylcholine (LPC)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) by activating glutathione peroxidase and superoxide dismutase, clearing intracellular reactive oxygen species (ROS), and reducing lipid peroxidation [21, 23]. Nonetheless, little is known about the effects of TSG on endothelial dysfunction in obesity.…”

AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia

“…200 μl supernatants were added into a 96 well plate to determine spectrophotometry at a 532 nm wavelength. MDA levels in HTR8/SVneo cells were determined as previously reported [20]. After treatment, HTR8/SVneo cells were harvested, washed with cold PBS and dissociated using trypsin.…”

Identification of antioxidant peptides derived from egg‐white protein and its protective effects on H2O2‐induced cell damage

“…The level of lipid oxidation can be reflected by the content of MDA, thus the MDA is widely used as an indicator of lipid oxidation (Jiang et al ., ). Superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) protect the body from oxidative damage and exist vital role in maintaining cell redox homeostasis (Zhao et al ., ). To investigate the mechanism of VYLPR, we determined the status of LDH, MDA, SOD and GSH‐Px treated with H 2 O 2 alone or in combination with different concentrations of VYLPR.…”