scholarly journals The Role of Nrf2 Signaling in PPARβ/δ-Mediated Vascular Protection against Hyperglycemia-Induced Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Rosario Jimenez ◽  
Marta Toral ◽  
Manuel Gómez-Guzmán ◽  
Miguel Romero ◽  
Manuel Sanchez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Dependent Manner ◽  
Vascular Protection ◽  
Concentration Dependent Manner

Hyperglycemia induces oxidative stress and plays a substantial role in the progression of vascular diseases. Here, we demonstrated the potentiality of peroxisome proliferator-activated receptor (PPAR)β/δ activation in attenuating high glucose-induced oxidative stress in endothelial cells and diabetic rats, pointing to the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2). HUVECs exposed to high glucose showed increased levels of reactive oxygen species (ROS) and upregulated NOX-2, NOX-4, Nrf2, and NQO-1 effects that were significantly reversed by the PPARβ/δ agonists GW0742 and L165041. Both PPARβ/δ agonists, in a concentration-dependent manner, induced transcriptional and protein upregulation of heme oxygenase-1 (HO-1) under low- and high-glucose conditions. All effects of PPARβ/δ agonists were reversed by either pharmacological inhibition or siRNA-based downregulation of PPARβ/δ. These in vitro findings were confirmed in diabetic rats treated with GW0742. In conclusion, PPARβ/δ activation confers vascular protection against hyperglycemia-induced oxidative stress by suppressing NOX-2 and NOX-4 expression plus a direct induction of HO-1; with the subsequent downregulation of the Nrf2 pathway. Thus, PPARβ/δ activation could be of interest to prevent the progression of diabetic vascular complications.

scholarly journals Ginsenoside Rg1 Protects Cardiomyocytes Against Hypoxia/Reoxygenation Injury via Activation of Nrf2/HO-1 Signaling and Inhibition of JNK

2017 ◽  
Vol 44 (1) ◽  
pp. 21-37 ◽  
Author(s):  
Qianhui Li ◽  
Yin Xiang ◽  
Yu Chen ◽  
Yong Tang ◽  
Yachen Zhang
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Ginsenoside Rg1 ◽  
H9c2 Cells ◽  
Stress Injury ◽  
Mitochondrial Membrane Depolarization ◽  
Hypoxia Reoxygenation

Background/Aims: Excessive reactive oxygen species (ROS) disturb the physiology of H9c2 cells, which is regarded as a major cause of H9c2 cardiomyocyte apoptosis. Ginsenoside Rg1 is the main active extract of ginseng, which has important antioxidant properties in various cell models. This project investigated the role of ginsenoside Rg1 in hypoxia/reoxygenation (H/R)-induced oxidative stress injury in cultured H9c2 cells to reveal the underlying signaling pathways. Methods: H9c2 cells were pretreated with ginsenoside Rg1 for 12 h before exposure to H/R. In the absence or presence of Nrf2siRNA, HO-1 inhibitor (ZnPP-IX), and inhibitors of the MAPK pathway (SB203580, PD98059, SP600125), H9c2 cells were subjected to H/R with Rg1 treatment. The effects and mechanisms of H/R-induced cardiomyocyte injury were measured. Results: Ginsenoside Rg1 treatment suppressed H/R-induced apoptosis and caspase-3 activation. Ginsenoside Rg1 treatment decreased ROS production and mitochondrial membrane depolarization by elevating the intracellular antioxidant capacity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH). Furthermore, ginsenoside Rg1 stimulation appeared to result in nuclear translocation of NF-E2-related factor 2 (Nrf2), along with enhanced expression of the downstream target gene heme oxygenase-1 (HO-1) in a dose-dependent manner. However, ginsenoside Rg1-mediated cardioprotection was abolished by Nrf2-siRNA and HO-1 inhibitor. H/R treatment increased the levels of phosphorylated c-Jun N-terminal kinases (p-JNK), which was dramatically attenuated by ginsenoside Rg1 and SP600125 (a specific JNK inhibitor). Conclusion: These observations indicate that ginsenoside Rg1 activates the Nrf2/HO-1 axis and inhibits the JNK pathway in H9c2 cells to protect against oxidative stress.

scholarly journals Protective Effect of Decursin Extracted fromAngelica gigasin Male Infertility via Nrf2/HO-1 Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Woong Jin Bae ◽  
U. Syn Ha ◽  
Jin Bong Choi ◽  
Kang Sup Kim ◽  
Su Jin Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Semen Quality ◽  
Antioxidant Activities ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Testicular Weight ◽  
Unilateral Cryptorchidism

Higher testicular temperature results in altered spermatogenesis due to heat-related oxidative stress. We examined the effects of decursin extracted fromAngelica gigasNakai on antioxidant activityin vitroand in a cryptorchidism-induced infertility rat model. TM3 Leydig cell viability was measured based on oxidative stress according to treatment. Either distilled water or AG 400 mg/kg ofA. gigasextract was administered orally for 4 weeks after unilateral cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control group and six rats from treatment group were sacrificed. Testicular weight, semen quality, antioxidant activities, nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and mRNA expression of Nrf2-regulated genes were analyzed. Treatment withA. gigasextract (1) protected TM3 cells against oxidative stress in a dose-dependent manner, (2) improved the mean weight of the cryptorchid testis, (3) maintained sperm counts, motility, and spermatogenic cell density, (4) decreased levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and increased levels of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme oxygenase-1 (HO-1), and (6) significantly decreased apoptosis. This study suggests that decursin extracted fromA. gigasis a supplemental agent that can reduce oxidative stress by Nrf2-mediated upregulation of HO-1 in rat experimentally induced unilateral cryptorchidism and may improve cryptorchidism-induced infertility.

HIGH GLUCOSE INDUCED BONE LOSS VIA ATTENUATING THE PROLIFERATION AND OSTEOBLASTOGENESIS AND ENHANCING ADIPOGENESIS OF BONE MARROW MESENCHYMAL STEM CELLS

2013 ◽  
Vol 25 (05) ◽  
pp. 1340010 ◽  
Author(s):  
Wen-Tyng Li ◽  
Wen-Kai Hu ◽  
Feng-Ming Ho
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Loss ◽  
High Glucose ◽  
Chromatin Condensation ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Bone Marrow Mscs

Diabetes mellitus (DM) is associated with bone loss and leads to osteopenia and osteoporosis. This study was undertaken to investigate whether the impaired functions of mesenchymal stem cells (MSCs) derived from bone marrow play a role in pathogenesis of DM-associated bone loss. Bone marrow MSCs were taken from the alloxan-induced diabetic rats and normal rats. Bone mineral densities of tibias and femurs in diabetic rats decreased compared to those of normal rats as shown by dual energy X-ray absorptiometry. MSCs from diabetic rats exhibited reduced colony formation activity. The in vitro effects of high glucose (HG) (20 or 33 mM) on the growth, oxidative stress, apoptosis, and differentiation MSCs were next assessed. The viability and proliferation of MSCs derived from diabetic rats decreased significantly compared with that from normal rats. HG further suppressed the proliferation and viability of MSCs from both diabetic and normal rats. HG was associated with 38–40% increase in reactive oxygen species level and had significantly downregulated the activities of superoxide dismutase (SOD) and catalase (CAT) which could be recovered by the addition of L-ascorbic acid. The phenomena of apoptosis such as chromatin condensation and DNA fragmentation were found in cells cultured under HG conditions. As compared with 5.5 mM glucose, exposure of MSCs to HG enhanced adipogenic induction of triacylglycerol accumulation and inhibited osteogenic induction of alkaline phosphatase activity. HG increased peroxisome proliferator-activated receptor gamma expression during adipogenesis and reduced RUNX2 expression during osteoblastogenesis. These results indicate that MSCs derived from diabetic rats exhibited the inhibitory effects on cell growth and osteogenic ability. The oxidative stress, apoptosis, and adipogenic capability of MSCs were increased by HG. Furthermore, it is suggested that HG induces bone loss via attenuating the proliferation and osteoblastogenesis and enhancing adipogenesis mediated by the oxidative stress in rat bone marrow MSCs.

scholarly journals The Protective Effect of Hispidin against Hydrogen Peroxide-Induced Oxidative Stress in ARPE-19 Cells via Nrf2 Signaling Pathway

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 380 ◽  
Author(s):  
Huang ◽  
Chang ◽  
Chau ◽  
Chiu
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Protective Effect ◽  
Retinal Pigment ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Glutamate Cysteine Ligase ◽  
Jnk Pathway ◽  
Nrf2 Signaling Pathway

Hispidin, a polyphenol compound isolated from Phellinus linteus, has been reported to possess antioxidant activities. In this study, we aimed to investigate the mechanisms underlying the protective effect of hispidin against hydrogen peroxide (H2O2)-induced oxidative stress on Adult Retinal Pigment Epithelial cell line-19 (ARPE-19) cells. Hispidin was not cytotoxic to ARPE-19 cells at concentrations of less than 50 μM. The levels of intracellular reactive oxygen species (ROS) were analyzed by dichlorofluorescin diacetate (DCFDA) staining. Hispidin significantly restored H2O2-induced cell death and reduced the levels of intracellular ROS. The expression levels of antioxidant enzymes, such as NAD(P)H:Quinine oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) were examined using real-time PCR and Western blotting. Our results showed that hispidin markedly enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1, NQO-1, GCLM, and GCLC in a dose-dependent manner. Furthermore, knockdown experiments revealed that transfection with Nrf2 siRNA successfully suppresses the hispidin activated Nrf2 signaling in ARPE-19 cells. Moreover, activation of the c-Jun N-terminal kinase (JNK) pathway is involved in mediating the protective effects of hispidin on the ARPE-19 cells. Thus, the present study demonstrated that hispidin provides protection against H2O2-induced damage in ARPE-19 cells via activation of Nrf2 signaling and up-regulation of its downstream targets, including Phase II enzymes, which might be associated with the activation of the JNK pathway.

scholarly journals S-Allyl Cysteine Alleviates Hydrogen Peroxide Induced Oxidative Injury and Apoptosis through Upregulation of Akt/Nrf-2/HO-1 Signaling Pathway in HepG2 Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Chitra Basu ◽  
Runa Sur
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Cell Viability Assay

Hydrogen peroxide (H2O2) mediated oxidative stress leading to hepatocyte apoptosis plays a pivotal role in the pathophysiology of several chronic liver diseases. This study demonstrates that S-allyl cysteine (SAC) renders cytoprotective effects on H2O2 induced oxidative damage and apoptosis in HepG2 cells. Cell viability assay showed that SAC protected HepG2 cells from H2O2 induced cytotoxicity. Further, SAC treatment dose dependently inhibited H2O2 induced apoptosis via decreasing the Bax/Bcl-2 ratio, restoring mitochondrial membrane potential (∆Ψm), inhibiting mitochondrial cytochrome c release, and inhibiting proteolytic cleavage of caspase-3. SAC protected cells from H2O2 induced oxidative damage by inhibiting reactive oxygen species accumulation and lipid peroxidation. The mechanism underlying the antiapoptotic and antioxidative role of SAC is the induction of the heme oxygenase-1 (HO-1) gene in an NF-E2-related factor-2 (Nrf-2) and Akt dependent manner. Specifically SAC was found to induce the phosphorylation of Akt and enhance the nuclear localization of Nrf-2 in cells. Our results were further confirmed by specific HO-1 gene knockdown studies which clearly demonstrated that HO-1 induction indeed played a key role in SAC mediated inhibition of apoptosis and ROS production in HepG2 cells, thus suggesting a hepatoprotective role of SAC in combating oxidative stress mediated liver diseases.

scholarly journals Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaojun Pang ◽  
Emmanuel Ayobami Makinde ◽  
Fredrick Nwude Eze ◽  
Opeyemi Joshua Olatunji
Keyword(s):  
Oxidative Stress ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Diabetic Encephalopathy ◽  
Y Maze ◽  
Securidaca Inappendiculata

Diabetic encephalopathy is one of the serious emerging complication of diabetes. Securidaca inappendiculata is an important medicinal plant with excellent antioxidant and anti-inflammatory properties. This study investigated the neuroprotective effects of S. inappendiculata polyphenol rich extract (SiPE) against diabetic encephalopathy in rats and elucidated the potential mechanisms of action. Type 2 diabetes mellitus (T2DM) was induced using high fructose solution/intraperitoneal injection of streptozotocin and the diabetic rats were treated with SiPE (50, 100 and 200 mg/kg) for 8 weeks. Learning and memory functions were assessed using the Morris water and Y maze tests, depressive behaviour was evaluated using forced swimming and open field tests, while neuropathic pain assessment was assessed using hot plate, tail immersion and formalin tests. After the experiments, acetylcholinesterase (AChE), oxidative stress biomarkers and proinflammatory cytokines, caspase-3 and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) were determined by ELISA kits. In addition, the expression levels of p38, phospho-p38 (p-p38), nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by western blot analyses. The results indicated that SiPE administration significantly lowered blood glucose level, attenuated body weight loss, thermal/chemical hyperalgesia, improved behavioural deficit in the Morris water maze, Y maze test and reduced depressive-like behaviours. Furthermore, SiPE reduced AChE, caspase-3, NF-κB, malonaldehyde malondialdehyde levels and simultaneously increased antioxidant enzymes activity in the brain tissues of diabetic rats. SiPE administration also significantly suppressed p38 MAPK pathway and upregulated the Nrf2 pathway. The findings suggested that SiPE exerted antidiabetic encephalopathy effects via modulation of oxidative stress and inflammation.

scholarly journals Cafestol Inhibits High-Glucose-Induced Cardiac Fibrosis in Cardiac Fibroblasts and Type 1-Like Diabetic Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ju-Chi Liu ◽  
Po-Yuan Chen ◽  
Wen-Rui Hao ◽  
Yi-Chung Liu ◽  
Ping-Chiang Lyu ◽  
...  
Keyword(s):  
High Glucose ◽  
Collagen Synthesis ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Biological Effects ◽  
Diabetic Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Tgf Β1

Diabetes is associated with the development of myocardial fibrosis, which is related to various cardiac diseases. Cafestol, one of the active ingredients in coffee, has been reported to exert biological effects. However, whether cafestol can ameliorate diabetes-induced cardiac fibrosis remains unknown. The aim of this study was to evaluate the effects of cafestol on cardiac fibrosis in high-glucose-treated cardiac fibroblasts and streptozocin- (STZ-) induced diabetic rats. Rat cardiac fibroblasts were cultured in high-glucose (25 mM) media in the absence or presence of cafestol, and the changes in collagen synthesis, transforming growth factor-β1 (TGF-β1) production, and related signaling molecules were assessed on the basis of 3H-proline incorporation, enzyme-linked immunosorbent assay, and western blotting. Cardiac fibroblasts exposed to high-glucose conditions exhibited increased collagen synthesis, TGF-β1 production, and Smad2/3 phosphorylation, and these effects were mitigated by cafestol treatment. Furthermore, cafestol increased the translocation of nuclear factor erythroid 2-related factor 2 and increased the expression of heme oxygenase-1. The results of molecular docking analysis suggested a selective interaction of cafestol with Kelch-like ECH-associated protein 1. The rats with untreated STZ-induced diabetes exhibited considerable collagen accumulation, which was ameliorated by cafestol. Moreover, activities of catalase, superoxide dismutase, general matrix metalloproteinase, and reduced glutathione concentration were upregulated, whereas malondialdehyde level was downregulated by treatment with cafestol in rats with cardiac fibrosis. These findings highlight the effects of cafestol, which may be useful in treating diabetes-related cardiac fibrosis.

Rutaecarpine Protects from Neuropathic Pain in a Rat Model of Chronic Compression Injury

2021 ◽  
Vol 19 (4) ◽  
pp. 409-414
Author(s):  
Guizhen Yan ◽  
Hongkun Zhai ◽  
Chunhua Hou ◽  
Chunli Xing
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Nerve Tissue ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Compression Injury ◽  
Stress Studies ◽  
Markers Of Oxidative Stress ◽  
Factor Α

Chronic compression injury elevates oxidative stress and inflammation leading to neuropathic pain that is alleviated by rutaecarpine in a dose-dependent manner. To understand the mechanism(s) underlying rutaecarpine effects on this process, changes in the expressions of the proteins and messenger ribonucleic acids for tumor necrosis factor-α, interlukin-6, and interleukin-1β were assessed. Also, the pathology of the sciatic nerve tissue was examined histologically. Furthermore, the expression of the levels of malondialdehyde, superoxide dismutase, and glutathione proteins were evaluated as markers of oxidative stress. Studies aimed at the understanding the mechanisms underlying actions of rutaecarpine suggested it to exert a protective effect on neuropathic pain in a chronic compression injury rat via activating nuclear-factor erythroid 2-related factor 2/Heme oxygenase-1 and inhibiting 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 gene pathways.

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.

Salvia miltiorrhiza Lipophilic Fraction Attenuates Oxidative Stress in Diabetic Nephropathy through Activation of Nuclear Factor Erythroid 2-Related Factor 2

2017 ◽  
Vol 45 (07) ◽  
pp. 1441-1457 ◽  
Author(s):  
Lin An ◽  
Mei Zhou ◽  
Faiz M. M. T. Marikar ◽  
Xue-Wen Hu ◽  
Qiu-Yun Miao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
High Glucose ◽  
Mesangial Cells ◽  
Salvia Miltiorrhiza ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor

Diabetic nephropathy (DN) is a common cause of chronic kidney disease and end-stage renal disease, which can be triggered by oxidative stress. In this study, we investigated the renoprotective effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on DN and examined the underlying molecular mechanism. We observed that EASM treatment attenuated metabolic abnormalities associated with hyperglycemic conditions in the experimental DN model. In streptozotocin (STZ)-induced mice, EASM treatment reduced albuminuria, improved renal function and alleviated the pathological alterations within the glomerulus. To mimic the hyperglycemic conditions in DN patients, we used high glucose (25[Formula: see text]mmol/L) media to stimulate mouse mesangial cells (MMCs), and EASM inhibited high glucose-induced reactive oxygen species. We also observed that EASM enhanced the expression of nuclear factor erythroid-2-related factor 2 (Nrf2), which mediated the anti-oxidant response, and its downstream gene heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) with concomitant decrease of expression of kelch-like ECH-associated protein 1 (keap1) both in vitro and in vivo. Taken together, these results suggest that EASM alleviates the progression of DN and this might be associated with activation of Nrf2.

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