scholarly journals Effects of Raspberry on Angiotensin II-Induced Oxidative Stress, Inflammation and Fibrosis in the Heart of Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 370-370
Author(s):  
Jasmynne Blacks ◽  
Rami Najjar ◽  
Christy Simecka ◽  
Shengyu Mu ◽  
Rafaela Feresin
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Saline Control ◽  
Related Factor ◽  
Nuclear Factor ◽  
Ang Ii ◽  
Funding Sources ◽  
Freeze Dried ◽  
Post Hoc ◽  
And Oxidative Stress

Abstract Objectives To investigate whether diet supplementation with raspberry attenuate angiotensin (Ang) II- induced increase in oxidative stress, inflammation, and fibrosis in the heart of mice. Methods Twelve-week male C57BL/6J mice were fed AIN-93M diets alone (control and Ang II groups) or supplemented with 10% w/w freeze-dried raspberry (n = 5 per group). At week 4, mice were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (Control) or Ang II (1 µg/kg body weight/day) for another four weeks. Heart was collected at sacrifice and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase (SOD)2, and interleukin (IL)-6 were measured. Fibrosis was assessed using Masson's trichrome staining. Results were analyzed using ANOVA followed by Tukey-Kramer post-hoc test. Effect size (d) was also calculated to compare standardized changes among groups. Results Protein expression of Nrf2, a transcription factor that regulates the expression of antioxidant enzymes, was up-regulated by raspberry (1.57 ± 0.34 vs. 0.76 ± 0.15-fold, P = 0.09, d = 1.4) compared to Ang II, albeit not significantly. Ang II did not change the protein expression of the antioxidant enzyme SOD2 in the heart; however, supplementation with raspberry increased SOD2 (1.81 ± 0.33 vs. 1.09 ± 0.09-fold, P = 0.09; d = 1.1) expression compared to Ang II, though not significantly. Supplementation with raspberry significantly attenuated protein expression of the inflammatory cytokine IL-6 compared to Ang II (0.87 ± 0.19 vs. 1.4 ± 0.10-fold, P = 0.04, d = 1.8). Lastly, Ang II increased fibrosis in the heart of mice, which was attenuated by supplementation with raspberry. Conclusions Our findings indicate that raspberry may decrease Ang II-induced fibrosis by decreasing inflammation and oxidative stress in the heart. Funding Sources Arkansas Biosciences Institute & Lewis Foundation Grant Award.

scholarly journals Blackberry and Raspberry Attenuate the Increase in Blood Pressure Elicited by Angiotensin II in Mice (P06-054-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Rafaela Feresin ◽  
Rami Najjar ◽  
Christy Simecka ◽  
Shengyu Mu
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Saline Control ◽  
Ang Ii ◽  
Nadph Oxidases ◽  
Funding Sources ◽  
Grant Program ◽  
Freeze Dried ◽  
Post Hoc ◽  
Tail Cuff

Abstract Objectives To examine whether diet supplementation with blackberry or raspberry attenuate angiotensin (Ang) II-induced increase in blood pressure (BP) and decrease oxidative stress in the kidneys of mice. Methods Twelve-week male C57BL/6 J mice were fed AIN-93 M diets alone (control and Ang II groups) or supplemented with 10% w/w freeze-dried blackberry (BL + Ang II) or raspberry (RB + Ang II) powder for eight weeks. At week 4, mice were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (Control) or Ang II (1 µg/kg body weight/day) for another four weeks. BP was measured weekly by tail-cuff plethysmography and validated by direct measurement at endpoint using a BP catheter. Kidney expression of pro-oxidant enzymes such as NADPH oxidases (Nox) and antioxidant enzymes such as superoxide dismutates (SOD) were also measured. Results were analyzed using ANOVA followed by Tukey-Kramer post-hoc test. Results As expected, Ang II significantly increased systolic BP (SBP; 185 ± 4, n = 6, vs 132 ± 2 mmHg, n = 5, P < 0.001) and diastolic BP (124 ± 4, n = 6, vs 96 ± 2 mmHg, n = 4, P < 0.001) compared to control. Supplementation with BL and RB significantly attenuated this increase in SBP (143 ± 7 mmHg, n = 5, P < 0.0001 and 137 ± 4 mmHg, n = 5, P < 0.0001, respectively) and DBP (100 ± 6 mmHg, n = 5, P < 0.003 and 90 ± 3 mmHg, n = 5, P < 0.0001, respectively). Regarding the expression of NADPH oxidases in the kidney, Nox2 was significantly decreased by supplementation with BL (0.68 ± 0.07-fold, n = 5, P = 0.0005) and RB (0.70 ± 0.03-fold, n = 5, P = 0.0008) compared to Ang II (1.15 ± 0.12-fold, n = 5). Nox1 expression was up-regulated by Ang II compared to control (2.03 ± 0.16 vs 1.00 ± 0.00-fold, n = 5, P = 0.0001), but this was not prevented by supplementation with either berry. Nox4 expression was not affected by any of the treatments. Lastly, Ang II did not change the expression of SOD1 and SOD2 in the kidney, however, supplementation with RB significantly increased SOD1 (P = 0.02) and SOD2 (P = 0.005) expression compared to the other groups. Conclusions Our findings indicate that supplementation with BL and RB decrease BP in mice which may be related to a decrease in oxidative stress in the kidney. Studies are underway to further elucidate the mechanism by which BL and RB exert their antihypertensive effects. Funding Sources Arkansas Biosciences Institute and Lewis Foundation Grant Program.

scholarly journals Raspberry Consumption Attenuates Angiotensin II-Induced Oxidative Stress in the Subfornical Organ in Male Sprague-Dawley Rats

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 298-298
Author(s):  
Jasmynne Blacks ◽  
Ferdinand Althammer ◽  
Rami Najjar ◽  
Maureen Meister ◽  
Jessica Dahn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subfornical Organ ◽  
Saline Control ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Funding Sources ◽  
Food Research ◽  
Food And Agriculture ◽  
Sprague Dawley Rats ◽  
Freeze Dried

Abstract Objectives To examine whether raspberry (RB) attenuates oxidative stress induced by angiotensin (Ang) II in the subfornical organ (SFO) of the brain in rats. Methods Male Sprague-Dawley rats were fed an AIN-93M diet with or without 10% w/w freeze-dried RB powder for seven weeks. At week 4, rats were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (Control) or Ang II (270 ng/kg body weight/day) for another three weeks. Brain region-specific tissue punches were collected from flash-frozen sections containing the SFO. NADPH oxidase (NOX) 2 and 4 and superoxide dismutase (SOD) 1 and 2 were measured in SFO using western blot. Results were analyzed using one-way ANOVA followed by Tukey post hoc test. Data were normalized to control and are expressed as means ± standard deviation. Results Ang II significantly increased NOX2 expression compared to control (1.24 ± 0.1, n = 5, vs 1.00 ± 0.07-fold, n = 3, P = 0.009) while RB supplementation significantly attenuated Ang II-induced increases in NOX2 (0.91 ± 0.05-fold, n = 4; P = 0.0006). Ang II also increased NOX4 expression compared to control (2.11 ± 1.2, n = 9, vs 0.98 ± 0.4-fold, n = 6, P = 0.04), but RB supplementation did not significantly attenuate this effect (1.30 ± 0.36-fold, n = 10, P = 0.11). RB increased expression of SOD1 (1.52 ± 0.20-fold, n = 4) compared to control (1.00 ± 0.15-fold, n = 3, P = 0.009) and Ang II alone (1.08 ± 0.16-fold, n = 5, P = 0.01). On the other hand, Ang II treatment decreased SOD2 expression compared to control (0.62 ± 0.05, n = 5, vs 1.00 ± 0.09-fold, n = 3, P = 0.0001), but the RB supplementation did not prevent this effect (0.72 ± 0.07-fold, n = 4, P = 0.16). Conclusions Our findings suggest that RB supplementation decreases Ang II-induced oxidative stress in the SFO by decreasing NOX2 and increasing SOD1 expression. Future investigations are warranted to elucidate the effects of RB on oxidative stress pathways in the SFO. Funding Sources This work was supported by the Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.

scholarly journals Raspberry Increases Expression of Antioxidant Enzymes in the Kidney of Angiotensin II-Treated Rats

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 341-341
Author(s):  
Lena MT Lear ◽  
Rami Najjar ◽  
Maureen Meister ◽  
Jessica Danh ◽  
Desiree Wanders ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Antioxidant Enzyme ◽  
Saline Control ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Funding Sources ◽  
Food Research ◽  
Food And Agriculture ◽  
Freeze Dried

Abstract Objectives To examine whether dietary supplementation with raspberries attenuates angiotensin (Ang) II-induced oxidative stress in the kidneys of rats. Methods Eight-week-old male Sprague-Dawley rats were fed an AIN-93M diet (control and Ang II groups) or AIN-93M diet supplemented with 10% w/w freeze-dried raspberry (RB + Ang II) for seven weeks. At week 4, rats were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (control) or Ang II (270 ng/kg body weight/day) for an additional three weeks. Protein expression of antioxidant enzymes, such as glutathione peroxidase 1 (GP × 1) and NADPH quinone dehydrogenase 1 (NQO1), as well as ERK1/2 phosphorylation were assessed by western blot in the kidneys. Results were analyzed using one-way ANOVA followed by Tukey-Kramer post hoc test. Data were normalized to control and are expressed as mean ± standard deviation. Results The expression of the antioxidant enzyme GP × 1 was significantly increased with raspberry supplementation (1.33 ± 0.24-fold, n = 9) in comparison to control (1.00 ± 0.18-fold, n = 9, P = 0.009) and Ang II alone (0.93 ± 0.24-fold, n = 9, P = 0.002). The expression of the antioxidant enzyme NQO1 was significantly increased with raspberry supplementation (2.10 ± 0.74-fold, n = 9) in comparison to control (1.00 ± 0.44-fold, n = 9, P = 0.0002) and Ang II alone (0.74 ± 0.16-fold, n = 9, P &lt; 0.0001). Although not significantly, Ang II induced an increase in ERK1/2 phosphorylation in comparison to control (1.66 ± 0.45 vs 1.00 ± 0.88-fold, n = 5, P = 0.22). Nonetheless, raspberry supplementation (0.62 ± 0.22-fold, n = 5, P = 0.02) was able to attenuate ERK1/2 phosphorylation in comparison to Ang II alone. Conclusions Our findings indicate that supplementation with raspberry has the potential to significantly increase the expression of antioxidant enzymes in a model of Ang II-induced oxidative stress. Future work will focus on elucidating the mechanism through which raspberries elicit their action in the kidneys. Funding Sources This work was supported by the Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.

scholarly journals Raspberry Consumption Increases Cardiac NRF2 Transcriptional Products in Angiotensin II-Infused Rats

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 351-351
Author(s):  
Rami Najjar ◽  
Maureen Meister ◽  
Jessica Danh ◽  
Lena MT Lear ◽  
Justina Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Corn Oil ◽  
Saline Control ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Funding Sources ◽  
Food Research ◽  
Food And Agriculture ◽  
Freeze Dried ◽  
Endogenous Antioxidant

Abstract Objectives To determine whether raspberry consumption mitigates cardiac oxidative stress induced by angiotensin (Ang) II in rats. Methods Eight-week-old male Sprague-Dawley rats were fed AIN-93M (4% corn oil) diets with or without a 10% w/w raspberry freeze-dried powder for seven weeks. At week 4, rats were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (control) or Ang II (270 ng/kg body weight/day). At week 7, hearts were excised for protein analysis via western blot. Protein expression of NRF2 and its transcriptional products, HO-1 and NQO1, were quantified in the left ventricle. Data are normalized to control and presented as mean ± standard deviation. Results were analyzed with one-way ANOVA followed by Tukey post hoc test if data were normally distributed. Otherwise, non-parametric Kruskal-Wallis test was conducted. Results The expression of the antioxidant transcription factor NRF2 was significantly increased by raspberry consumption compared with Ang II alone (2.41 ± 0.62, n = 5 vs 1.31 ± 0.20-fold, n = 5, P = 0.002) and compared to control (1.00 ± 0.19-fold, n = 5, P = 0.0003). Additionally, the expression of NRF2 transcriptional product NQO1 was significantly increased by raspberry consumption compared to control (1.70 ± 0.52, n = 5 vs 1.00 ± 0.41-fold, n = 5, P = 0.05) but not compared to Ang II (1.30 ± 0.25-fold, n = 5, P = 0.3). Lastly, HO-1 was significantly increased in rats consuming raspberries compared to control (3.04 ± 1.80, n = 5 vs 1.00 ± 0.23-fold, n = 5, P = 0.02), but not compared to Ang II alone (1.92 ± 1.06-fold, n = 5, P = 0.8). Conclusions Raspberries directly increase NRF2 and its transcriptional products in the hearts of rats infused with Ang II. These findings may translate to cardio-protection from neurohumoral insult due to reduced oxidative stress and increased endogenous antioxidant enzyme activity. Funding Sources This work was supported by the Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.

Neuroprotection of chromobox 7 knockout in the mouse after cerebral ischemia-reperfusion injury via nuclear factor E2-related factor 2/hemeoxygenase-1 signaling pathway

2021 ◽  
pp. 096032712110361
Author(s):  
Hai-Tao Zhang ◽  
Xi-Zeng Wang ◽  
Qing-Mei Zhang ◽  
Han Zhao
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Water Content ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cerebral Ischemia Reperfusion ◽  
And Oxidative Stress

Objective To explore the mechanism of chromobox 7 (CBX7)-mediated nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway in the cerebral ischemia/reperfusion (I/R) injury. Methods The experimental wild-type (WT) and CBX7-/- mice were used to establish cerebral I/R models using the middle cerebral artery occlusion (MCAO) surgery to determine CBX7 levels at different time points after MCAO injury. For all mice, neurological behavior, infarct size, water content, and oxidative stress–related indicators were determined, and transferase (TdT)-mediated dUTP-biotin nick-end labeling (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)) staining method was employed to observe cell apoptosis, while Western blot to measure the expression of CBX7 and Nrf/HO-1 pathway-related proteins. Results At 6 h, 12 h, 24 h, 3 days, and 7 days after mice with MCAO, CBX7 expression was gradually up-regulated and the peak level was reached at 24 h. Mice in the WT + MCAO group had increased infarct size, with significant increases in the modified neurological severity scores and water content in the brain, as well as the quantity of TUNEL-positive cells. For the oxidative stress-indicators, an increase was seen in the content of MDA (malondial dehyde), but the activity of SOD (superoxide dismutase) and content of GSH-PX (glutathione peroxidase) and CAT (catalase) were decreased; meanwhile, the protein expression of CBX7, HO-1, and nuclear Nrf2 was up-regulated, while the cytoplasmic Nrf2 was down-regulated. Moreover, CBX7 knockout attenuated I/R injury in mice. Conclusion Knockout of CBX7 may protect mice from cerebral I/R injury by reducing cell apoptosis and oxidative stress, possibly via activating the Nrf2/HO-1 pathway.

scholarly journals Isoliquiritigenin Confers Neuroprotection and Alleviates Amyloid-β42-Induced Neuroinflammation in Microglia by Regulating the Nrf2/NF-κB Signaling

2021 ◽  
Vol 15 ◽  
Author(s):  
Yue Fu ◽  
Jianping Jia
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
No Production ◽  
Related Factor ◽  
Nuclear Factor ◽  
Qrt Pcr ◽  
Bv2 Cells ◽  
And Oxidative Stress

BackgroundNeuroinflammation and oxidative stress are two major pathological characteristics of Alzheimer’s disease (AD). Amyloid-β oligomers (AβO), a toxic form of Aβ, promote the neuroinflammation and oxidative stress in the development of AD. Isoliquiritigenin (ISL), a natural flavonoid isolated from the root of liquorice, has been shown to exert inhibitory effects on inflammatory response and oxidative stress.ObjectivesThe main purpose of this study is to assess the influence of ISL on inflammatory response and oxidative stress in BV2 cells stimulated with AβO, and to explore the underlying molecular mechanisms.Methods3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H- tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) cytotoxicity assays were used to assess the toxic or protective effects of ISL. The expression levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays. Morphological changes in BV2 cells were assessed by immunofluorescence method. Nitric oxide (NO) assay kit was used to determinate the NO production. Western blot, qRT-PCR and immunofluorescence were used to explore the underlying molecular mechanisms.ResultsISL treatment reduced the production of inflammatory cytokines and NO, and alleviated the morphological changes in BV2 cells induced by AβO. ISL treatment further protected N2a cells from the toxic medium of AβO-stimulated BV2 cells. ISL activated nuclear factor erythroid-2 related factor 2 (Nrf2) signaling and suppressed nuclear factor-κB (NF-κB) signaling in BV2 cells.ConclusionISL suppresses AβO-induced inflammation and oxidative stress in BV2 cells via the regulation of Nrf2/NF-κB signaling. Therefore, ISL indirectly protects neurons from the damage of toxic conditioned media.

scholarly journals Raspberry Consumption Decreases NOX4 Expression and Increases Antioxidant Enzymes in Lungs of Angiotensin II-Infused Rats

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 347-347
Author(s):  
Maureen Meister ◽  
Rami Najjar ◽  
Jessica Danh ◽  
Lena MT Lear ◽  
Justina Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Complementary Therapy ◽  
Saline Control ◽  
Heme Oxygenase 1 ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Food Research ◽  
Sd Rats ◽  
Freeze Dried

Abstract Objectives To determine whether a diet supplemented with red raspberry (RB) is effective at reducing angiotensin (Ang) II-induced oxidative stress in the lungs of Sprague Dawley (SD) rats. Methods Eight-week-old male SD rats were fed an AIN-93M diet alone (control and Ang II) or supplemented with 10% w/w freeze-dried RB powder for a total of seven weeks. At week 4, SD rats were implanted with subcutaneous osmotic minipumps for delivery of 0.9% saline (control) or Ang II (270 ng/kg body weight/day). Following 3 weeks of infusion, rats were sacrificed, and lungs were collected for analysis. Protein expression of the pro-oxidant enzyme, NADPH oxidase (NOX) 4, and antioxidant enzymes superoxide dismutase 1 (SOD1), catalase, heme oxygenase-1 (HO-1), and NADPH quinone dehydrogenase 1 (NQO1) were assessed by western blot. Results were analyzed by one-way ANOVA followed by Tukey post-hoc test. Results were normalized to control and presented as means ± standard deviation. Results RB supplementation significantly increased the expression of antioxidant enzymes, including, SOD1 (1.34 ± 0.16, n = 5, vs 1.11 ± 0.13-fold, n = 5, P = 0.04) and catalase (1.50 ± 0.28, n = 5, vs 0.79 ± 0.20-fold, n = 5, P = 0.008), when compared to Ang II alone. Compared to control, however, RB significantly increased SOD1 (1.00 ± 0.05-fold, n = 4, P = 0.004) while catalase did not (1.00 ± 0.40, n = 4, P = 0.07). Similarly, HO-1 (1.66 ± 0.82, n = 5, vs 0.75 ± 0.13-fold, n = 4, P = 0.046) and NQO1 (2.13 ± 0.19, n = 4, vs 1.26 ± 0.14-fold, n = 5, P &lt; 0.0001) were greater in the RB supplemented rats in comparison to Ang II alone. Additionally, RB significantly increased NQO1 (1.00 ± 0.16, n = 4, P &lt; 0.0001) but not HO-1 (1.00 ± 0.43-fold, n = 4, P = 0.22) when compared to control. RB supplementation also decreased the expression of NOX4 (0.77 ± 0.38, n = 5, vs 1.41 ± 0.30-fold, n = 5, P = 0.02) in comparison to Ang II alone. Conclusions Our results suggest the potential for red raspberries to decrease oxidative stress within the lung tissue. As investigations into whole food dietary treatments in lung conditions are essentially non-existent, future work will aim to determine the potential for raspberries to serve as a complementary therapy in these conditions. Funding Sources This work was funded by the Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.

scholarly journals Oridonin Attenuates Low Shear Stress-Induced Endothelial Cell Dysfunction and Oxidative Stress by Activating The Nuclear Factor Erythroid 2-Related Factor 2 Pathway

2021 ◽  
Author(s):  
ZHIPENG CHEN ◽  
HEQIAN LIU ◽  
SUBINUR MAMATELI ◽  
CHENG LIU ◽  
YUTONG LIU ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Related Factor ◽  
Nuclear Factor ◽  
Expression Levels ◽  
Low Shear Stress ◽  
Ea.Hy926 Cells ◽  
And Oxidative Stress ◽  
Mrna Expression Levels ◽  
Low Shear

Abstract Background Atherosclerosis (AS) is the primary cause of cardiovascular disease and the incidence is extremely common; however, there are currently few drugs that can effectively treat AS. Although oridonin has been widely used to treat inflammation and cancer for numerous years, to the best of our knowledge, its protective effect against AS has not been reported. Therefore, the present study aimed to investigate whether oridonin attenuated AS. Methods By using text mining, chemometric and chemogenomic methods, oridonin was predicted to be a beneficial agent for the treatment of AS. A parallel flow chamber was used to establish a low shear stress (LSS)-induced endothelial cell (EC) dysfunction model. Briefly, ECs were exposed to 3 dyn/cm2 LSS for 30 min and subsequently treated with oridonin or transfected with a small interfering RNA (siRNA) targeting nuclear factor erythroid 2-related factor 2 (NRF2). Reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) and glutathione disulfide (GSSG) in EA.hy926 cells were analyzed to determine the level of oxidative stress. The nitric oxide (NO) levels and mRNA expression levels of endothelial NO synthase (eNOS), endothelin-1 (ET-1) and prostaglandin synthase (PGIS) in EA.hy926 cells were analyzed to determine EC dysfunction. Furthermore, the mRNA expression levels of NRF2 were analyzed using reverse transcription-quantitative PCR. In addition, zebrafish were fed with a high-cholesterol diet to establish a zebrafish AS model, which was used to observe lipid accumulation and inflammation under a fluorescence microscope. Results We found LSS led to oxidative stress and EC dysfunction; this was primarily indicated through the significantly decreased SOD and GSH content, the significantly increased MDA, GSSG and ROS content, the upregulated mRNA expression levels of ET-1, and the downregulated NO levels and mRNA expression levels of eNOS and PGIS in ECs. Notably, oridonin could improve LSS-induced oxidative stress and EC dysfunction,and the effects of oridonin were reversed by the transfection with NRF2 siRNA. Oridonin also attenuated lipid accumulation and neutrophil recruitment at the LSS regions in the zebrafish AS model. Conclusions In conclusion, the results of the present study suggested that oridonin may ameliorate LSS-induced EC dysfunction and oxidative stress by activating NRF2, thereby attenuating AS.

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