scholarly journals Antioxidant and Cytoprotective Properties of Polyphenol-Rich Extracts from Antirhea borbonica and Doratoxylon apetalum against Atherogenic Lipids in Human Endothelial Cells

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 34
Author(s):  
Jonathan Bonneville ◽  
Philippe Rondeau ◽  
Bryan Veeren ◽  
Julien Faccini ◽  
Marie-Paule Gonthier ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Ldl Oxidation ◽  
Total Phenol Content ◽  
Low Density ◽  
Dependent Manner ◽  
Reunion Island ◽  
Atheromatous Plaques ◽  
Réunion Island ◽  
Intracellular Oxidative Stress

The endothelial integrity is the cornerstone of the atherogenic process. Low-density lipoprotein (LDL) oxidation occurring within atheromatous plaques lead to deleterious vascular effects including endothelial cell cytotoxicity. The aim of this study was to evaluate the vascular antioxidant and cytoprotective effects of polyphenol-rich extracts from two medicinal plants from the Reunion Island: Antirhea borbonica (A. borbonica), Doratoxylon apetalum (D. apetalum). The polyphenol-rich extracts were obtained after dissolving each dry plant powder in an aqueous acetonic solution. Quantification of polyphenol content was achieved by the Folin–Ciocalteu assay and total phenol content was expressed as g gallic acid equivalent/100 g plant powder (GAE). Human vascular endothelial cells were incubated with increasing concentrations of polyphenols (1–50 µM GAE) before stimulation with oxidized low-density lipoproteins (oxLDLs). LDL oxidation was assessed by quantification of hydroperoxides and thiobarbituric acid reactive substances (TBARS). Intracellular oxidative stress and antioxidant activity (catalase and superoxide dismutase) were measured after stimulation with oxLDLs. Cell viability and apoptosis were quantified using different assays (MTT, Annexin V staining, cytochrome C release, caspase 3 activation and TUNEL test). A. borbonica and D. apetalum displayed high levels of polyphenols and limited LDL oxidation as well as oxLDL-induced intracellular oxidative stress in endothelial cells. Polyphenol extracts of A. borbonica and D. apetalum exerted a protective effect against oxLDL-induced cell apoptosis in a dose-dependent manner (10, 25, and 50 µM GAE) similar to that observed for curcumin, used as positive control. All together, these results showed significant antioxidant and antiapoptotic properties for two plants of the Reunion Island pharmacopeia, A. borbonica and D. apetalum, suggesting their therapeutic potential to prevent cardiovascular diseases by limiting LDL oxidation and protecting the endothelium.

scholarly journals CYP1B1 expression promotes the proangiogenic phenotype of endothelium through decreased intracellular oxidative stress and thrombospondin-2 expression

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 744-754 ◽  
Author(s):  
Yixin Tang ◽  
Elizabeth A. Scheef ◽  
Shoujian Wang ◽  
Christine M. Sorenson ◽  
Craig B. Marcus ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Endothelial Cells ◽  
Retinopathy Of Prematurity ◽  
Cellular Responses ◽  
Retinal Endothelial Cells ◽  
Capillary Morphogenesis ◽  
Ischemic Retinopathy ◽  
Intracellular Oxidative Stress

Abstract Reactive species derived from cell oxygenation processes play an important role in vascular homeostasis and the pathogenesis of many diseases including retinopathy of prematurity. We show that CYP1B1-deficient (CYP1B1−/−) mice fail to elicit a neovascular response during oxygen-induced ischemic retinopathy. In addition, the retinal endothelial cells (ECs) prepared from CYP1B1−/− mice are less adherent, less migratory, and fail to undergo capillary morphogenesis. These aberrant cellular responses were completely reversed when oxygen levels were lowered or an antioxidant added. CYP1B1−/− ECs exhibited increased oxidative stress and expressed increased amounts of the antiangiogenic factor thrombospondin-2 (TSP2). Increased lipid peroxidation and TSP2 were both observed in retinas from CYP1B1−/− mice and were reversed by administration of an antioxidant. Reexpression of CYP1B1 in CYP1B1−/− ECs resulted in down-regulation of TSP2 expression and restoration of capillary morphogenesis. A TSP2 knockdown in CYP1B1−/− ECs also restored capillary morphogenesis. Thus, CYP1B1 metabolizes cell products that modulate intracellular oxidative stress, which enhances production of TSP2, an inhibitor of EC migration and capillary morphogenesis. Evidence is presented that similar changes occur in retinal endothelium in vivo to limit neovascularization.

Protective Effects of Berberine against Low-Density Lipoprotein (LDL) Oxidation and Oxidized LDL-Induced Cytotoxicity on Endothelial Cells

2007 ◽  
Vol 55 (25) ◽  
pp. 10437-10445 ◽  
Author(s):  
Yih-Shou Hsieh ◽  
Wu-Hsien Kuo ◽  
Ta-Wei Lin ◽  
Horng-Rong Chang ◽  
Teseng-His Lin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Low Density ◽  
Protective Effects

Autophagy and Apoptosis in the Response of Human Vascular Endothelial Cells to Oxidized Low-Density Lipoprotein

Cardiology ◽  
2015 ◽  
Vol 132 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Yanlin Zhang ◽  
Ying Xie ◽  
Shoujiang You ◽  
Qiao Han ◽  
Yongjun Cao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
P53 Protein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Positive Staining ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Concentration Dependent Manner

Objectives: Oxidized low-density lipoprotein (ox-LDL) may induce autophagy, apoptosis, necrosis or proliferation of cultured endothelial cells depending on the concentration and exposure time. Our previous studies found that ox-LDL exposure for 6 h increases the autophagic level of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. The present study investigates the relationship between autophagy and apoptosis in HUVECs exposed to ox-LDL. Methods: Flow cytometry and Western blot were used to study the apoptotic and autophagic phenomena. The contribution of autophagic and apoptotic mechanisms to ox-LDL-induced upregulation of MAP1-LC3, beclin1 and p53 protein levels were assessed by pretreatment with the autophagic inhibitors 3-MA and Atg5 small interfering (si)RNA, as well as z-vad-fmk, an apoptosis inhibitor. Results: ox-LDL induced the apoptosis of HUVECs in a concentration-dependent way. The increased expression of the autophagic proteins, LC3-II and beclin1, can be reversed by 3-MA and z-vad-fmk pretreatment. 3-MA and Atg5 siRNA increased the ox-LDL-induced increases of the p53 protein level and the annexin V-positive staining, which was decreased by z-vad-fmk. Conclusion: These results suggest that overstimulation of ox-LDL can induce autophagy and apoptosis in HUVECs. Inhibition of apoptosis leads to an inhibition of autophagy induced by ox-LDL. However, inhibition of autophagy leads to an increase in the ox-LDL-induced apoptosis.

Increased reactive oxygen species production with antisense oligonucleotides directed against uncoupling protein 2 in murine endothelial cells

2002 ◽  
Vol 80 (6) ◽  
pp. 757-764 ◽  
Author(s):  
Carine Duval ◽  
Anne Nègre-Salvayre ◽  
Alain Doglio ◽  
Robert Salvayre ◽  
Luc Pénicaud ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Antisense Oligonucleotides ◽  
Uncoupling Protein ◽  
Reactive Oxygen ◽  
Ldl Oxidation ◽  
Uncoupling Protein 2 ◽  
Thiobarbituric Acid Reactive Substance ◽  
Oxygen Species

Uncoupling protein 2 (UCP-2) belongs to the mitochondrial anion carrier family. It is ubiquitously expressed but is most abdundant in the reticuloendothelial system. In addition to uncoupling function, UCP-2 modulates the production of reactive oxygen species (ROS) by isolated mitochondria. Using an antisense oligonucleotide strategy, we investigated whether a defect in UCP-2 expression modulates ROS in intact endothelial cells. Murine endothelial cells (CRL 2181) pretreated by antisense oligonucleotides directed against UCP-2 mRNA exhibited a significant and specific increase in membrane potential and intracellular ROS level compared with control scrambled or anti-UCP-1 and -UCP-3 antisense oligonucleotides. These specific changes induced by UCP-2 antisense oligonucleotides were correlated with a rise in extracellular superoxide anion production and oxidative stress assessed by thiobarbituric acid reactive substance values. Taken together, these data suggest a role for UCP-2 in control of ROS production and subsequent oxidation of surrounding compounds mediating oxidative stress of endothelial cells. These data also support the notion that manipulations of UCP-2 at the genetic level could control ROS metabolism at the cellular level.Key words: UCP-2, reactive oxygen species, LDL oxidation, oxidative stress, mitochondria, endothelial cells.

scholarly journals The protection of LingqiHuangban Granule on human retinal endothelial cells against oxidative stress-induced injury by network pharmacology

2020 ◽  
Author(s):  
Zhenzhen Zhang ◽  
Chuandi Zhou ◽  
Deji Draga ◽  
lhamo Thashi ◽  
Zhi Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Caspase 3 ◽  
Network Pharmacology ◽  
High Dose ◽  
Dependent Manner ◽  
Retinal Endothelial Cells ◽  
Holistic Treatment ◽  
Protein Protein Interaction

Abstract Background: LingqiHuangban Granule(LQHBG) is a famous traditional Chinese medicine formula used to manage retinal diseases, as an effective holistic treatment through warming Yang to exert tonifying effects on kidney and invigorating spleen to remove dampness to nourish essence of effect. The study examined protection of LQHBG on oxidative stress-induced injury in human retinal endothelial cells(HRECs) in vitro, determined the potential molecular targets of LQHBG using network pharmacology.Methods: The potential targets of active ingredients in LQHBG were predicted using pharmmapper. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out using Molecule Annotation System. The protein-protein interaction networks were constructed using Cytoscape. LQHBG was administered to rabbits to prepare medicated serum. The apoptosis of HRECs was evaluated by TUNEL and Flow Cytometry(FCM). MDA, SOD, LDH, GSH-Px, and T-AOC were detected. The mRNA expressions of Nrf2, NF-κB and HO-1 were detected, protein expression levels of Nrf2, Bcl-2, NF-κB, HO-1 and caspase-3 were analyzed.Results: TUNEL demonstrated the numbers of apoptotic cells in low-and high-dose LQHBG groups was obviously less than model group(P<0.05). FCM analysis revealed apoptotic rates of HRECs in low-and high-dose LQHBG groups were obviously reduced in a dose-dependent manner(P<0.05). The potential mechanism of LQHBG was the NF-κB pathway identified using PharmMapper. LQHBG significantly decreased MDA, LDH levels and enhanced SOD, GSH-Px and T-AOC generation. LQHBG inhibited upregulation of NF-κB, caspase-3 and enhanced Bcl-2, Nrf2, and HO-1 expression.Conclusion: LQHBG protected HRECs against oxidative-stress via suppression of apoptosis and elevation of antioxidant ability, which may involve activation of Nrf2/ARE/HO-1 pathway and inhibition of NF-κB pathway.

Abstract 15015: Eicosapentaenoic Acid, but Not Docosahexaenoic Acid or a Mixed Omega-3 Fatty Acid Supplement, Inhibits Low-density Lipoprotein Oxidation in a Time-dependent Manner

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Samuel Sherratt ◽  
Peter Libby ◽  
Deepak L Bhatt ◽  
Preston Mason
Keyword(s):  
Antioxidant Activity ◽  
Fatty Acid ◽  
Eicosapentaenoic Acid ◽  
Time Dependent ◽  
Ldl Oxidation ◽  
Gas Chromatography Mass Spectrometry ◽  
Low Density ◽  
Dependent Manner ◽  
Omega 3 ◽  
Omega 3 Fatty Acid

Background: Eicosapentaenoic acid (EPA), an omega-3 fatty acid (O3FA), reduces oxidation of low-density lipoproteins (LDL) in patients with hypertriglyceridemia, an effect that may contribute to lower cardiovascular (CV) events as reported in the REDUCE-IT trial. By contrast, DHA-containing products have failed to show a reduction in CV events, which may be due, in part, to differences in antioxidant activity. We compared the effects of EPA versus DHA and a mixed O3FA (EPA/DHA) supplement on oxidation of human LDL in vitro . Methods: LDL was isolated from human plasma by isopycnic centrifugation, separated into test samples of 100 μg/mL, and incubated at 37°C for 30 min in the absence (vehicle) or presence of EPA, DHA, or mixed O3FA supplement at equimolar levels (2.5 μM). All samples were then subjected to copper-induced oxidation (20 μM) as measured by formation of malondialdehyde (MDA). The FA content of the O3FA supplement was measured using gas chromatography/mass spectrometry. Results: EPA significantly inhibited LDL oxidation in a time-dependent manner compared with vehicle; after 4 hours, EPA inhibited MDA levels by 96% compared with the vehicle oxidation level (0.51 ± 0.01 vs 11.4 ± 0.4 μM; p <0.001). While DHA exhibited antioxidant activity at 2 hours at a level below EPA (2.5 ± 0.1 vs 11.4 ± 0.4; p <0.001), even this level of activity was lost by 4 hours. The mixed O3FA supplement failed to show any antioxidant activity through 4 hours (11.4 ± 0.5 μM). Fatty acid analysis showed that the O3FA supplement, in addition to EPA and DHA, contained more than 30 other fatty acids, including saturated fats, that may have nullified any potential benefits. Conclusions: These data support potent LDL antioxidant effects of EPA that were sustained over time compared with DHA, which had a weaker, transient effect, or a mixed O3FA supplement, which had no beneficial effect at all. This potent antioxidant mechanism of EPA may contribute to reduced CV risks seen in REDUCE-IT compared with negative findings from trials using DHA-containing formulations.

The protective effect of daidzein on high glucose-induced oxidative stress in human umbilical vein endothelial cells

2016 ◽  
Vol 71 (1-2) ◽  
pp. 21-28 ◽  
Author(s):  
Mi Hwa Park ◽  
Jae-Won Ju ◽  
Mihyang Kim ◽  
Ji-Sook Han
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Protective Effect ◽  
High Glucose ◽  
Umbilical Vein ◽  
Vascular Complications ◽  
Dependent Manner ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

AbstractEndothelial cell dysfunction is considered a major cause of vascular complications in diabetes. In the present study, we investigated the protective effect of daidzein, a natural isoflavonoid, against high-glucose–induced oxidative damage in human umbilical vein endothelial cells (HUVECs). Treatment with a high concentration of glucose (30 mM) induced oxidative stress in the endothelial cells, against which daidzein protected the cells as demonstrated by significantly increased cell viability. In addition, lipid peroxidation, intracellular reactive oxygen species (ROS) generation, and indirect nitric oxide levels induced by the high glucose treatment were significantly reduced in the presence of daidzein (0.02–0.1 mM) in a dose-dependent manner. High glucose levels induced the overexpression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and NF-κB proteins in HUVECs, which was suppressed by treatment with 0.04 mM daidzein. These findings indicate the potential of daidzein to reduce high glucose-induced oxidative stress.

Coordinate regulation of endothelin and adrenomedullin secretion by oxidative stress in endothelial cells

2001 ◽  
Vol 281 (3) ◽  
pp. H1364-H1371 ◽  
Author(s):  
Takatoshi Saito ◽  
Hiroshi Itoh ◽  
Tae-Hwa Chun ◽  
Yasutomo Fukunaga ◽  
Jun Yamashita ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Mrna Expression ◽  
Vascular Diseases ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Camp Pathway ◽  
Intracellular Ca ◽  
Dose Dependent Fashion ◽  
Dose Dependent

To elucidate the significance of oxidative stress in the modulation of endothelial functions, we examined the effects of H2O2 on the expression of two endothelium-derived vasoactive peptides, endothelin (ET) and adrenomedullin (Am), and their interaction. H2O2 dose dependently suppressed ET secretion and ET-1 mRNA expression in bovine carotid endothelial cells (ECs). Menadion sodium bisulfate, a redox cycling drug, also decreased ET secretion in a dose-dependent manner. Catalase, a H2O2 reductase, and dl-α-tocopherol (vitamin E) significantly inhibited H2O2-induced suppression of ET secretion. Downregulation of ET-1 mRNA under oxidative stress was regulated at the transcriptional level. In contrast, H2O2increased Am secretion (and its mRNA expression) accompanied by the augmentation of cAMP production. Am, as well as 8-bromo-cAMP and forskolin decreased ET secretion in a dose-dependent fashion. Furthermore, an anti-Am monoclonal antibody that we developed abolished H2O2-induced suppression of ET secretion at 6–24 h after the addition of H2O2. H2O2 increased the intracellular Ca2+ concentration ([Ca2+]i). Moreover, treatment with ionomycin, a Ca2+ ionophore, and thapsigargin, an inhibitor of endoplasmic reticulum ATPase, decreased ET secretion dose dependently for 3 h. These results suggest that the production of ET was decreased via activation of the Am-cAMP pathway and by the elevation of [Ca2+]i under oxidative stress. These findings elucidate the coordinate expression of two local vascular hormones, ET and Am, under oxidative stress, which may protect against vascular diseases.

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