scholarly journals Cudratricusxanthone O Inhibits H2O2-Induced Cell Damage by Activating Nrf2/HO-1 Pathway in Human Chondrocytes

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 788 ◽  
Author(s):  
Eun-Nam Kim ◽  
Hyun-Su Lee ◽  
Gil-Saeng Jeong
Keyword(s):  
Cell Damage ◽  
Protoporphyrin Ix ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Ros Accumulation ◽  
Tin Protoporphyrin ◽  
Induced Apoptosis ◽  
Radical Damage

Osteoarthritis (OA) is a common joint degenerative disease induced by oxidative stress in chondrocytes. Although induced-heme oxygenase-1 (HO-1) has been found to protect cells against oxygen radical damage, little information is available regarding the use of bioactive compounds from natural sources for regulating the HO-1 pathway to treat OA. In this study, we explored the inhibitory effects of cudratricusxanthone O (CTO) isolated from the Maclura tricuspidata Bureau (Moraceae) on H2O2-induced damage of SW1353 chondrocytes via regulation of the HO-1 pathway. CTO promoted HO-1 expression by enhancing the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus without inducing toxicity. Pretreatment with CTO-regulated reactive oxygen species (ROS) production by inducing expression of antioxidant enzymes in H2O2-treated cells and maintained the functions of H2O2-damaged chondrocytes. Furthermore, CTO prevented H2O2-induced apoptosis by regulating the expression of anti-apoptotic proteins. Treatment with the HO-1 inhibitor tin-protoporphyrin IX revealed that these protective effects were exerted due to an increase in HO-1 expression induced by CTO. In conclusion, CTO protects chondrocytes from H2O2-induced damages—including ROS accumulation, dysfunction, and apoptosis through activation of the Nrf2/HO-1 signaling pathway in chondrocytes and, therefore, is a potential therapeutic agent for OA treatment.

scholarly journals Effects of Four Compounds from Gentianella acuta (Michx.) Hulten on Hydrogen Peroxide-Induced Injury in H9c2 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Kai Ren ◽  
He Su ◽  
Li-juan Lv ◽  
Le-tai Yi ◽  
Xue Gong ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Protein Expression ◽  
Treated Group ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Mtt Method ◽  
Bioassay Guided Fractionation ◽  
Induced Apoptosis

In previous studies, Gentianella acuta (Michx.) Hulten was reported to contain xanthones, iridoids, terpenoids, and sterols and is mainly used to cure hepatitis, jaundice, fever, headache, and angina pectoris. In this study, we used bioassay guided fractionation to identify compounds from G. acuta and investigated their activity against hydrogen peroxide (H2O2)-induced apoptosis of H9c2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic (GCLC) expression were assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated using western blot. The results showed that all four compounds had protective effects on H9c2 cells. The transcription levels of HO-1 and GCLC significantly increased in H9c2 cells pretreated with norswertianolin (1), swetrianolin (2), demethylbellidifolin (3), and bellidifolin (4). However, compared to the model group, the transcription levels of Nrf2 were not enhanced by pretreatment with compounds 1, 2, and 4. The protein expression levels of HO-1 and GCLC in H9c2 cells were greater than that in the H2O2-treated group, and the expression of Nrf2 was not significantly changed except by swetrianolin treatment; inhibitors can reverse the protective effect by ZnPP (15 μM), BSO (10 μM), and brusatol (10 μM). The results indicated that the four compounds isolated from G. acuta inhibited the oxidative injury induced by H2O2 by activating the Nrf2/ARE pathway in H9c2 cells and provide evidence that G. acuta may be a potential therapeutic agent for the treatment of cardiovascular diseases.

scholarly journals Synergistic Protection by Isoquercitrin and Quercetin against Glutamate-Induced Oxidative Cell Death in HT22 Cells via Activating Nrf2 and HO-1 Signaling Pathway: Neuroprotective Principles and Mechanisms of Dendropanax morbifera Leaves

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 554
Author(s):  
Hye-Jin Park ◽  
Ha-Neul Kim ◽  
Chul Young Kim ◽  
Min-Duk Seo ◽  
Seung-Hoon Baek
Keyword(s):  
Cell Death ◽  
Nuclear Translocation ◽  
Interaction Analysis ◽  
Cell Model ◽  
Antioxidant Compounds ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Ht22 Cells ◽  
Dendropanax Morbifera

Dendropanax morbifera leaves (DML) have long been used as traditional medicine to treat diverse symptoms in Korea. Ethyl acetate-soluble extracts of DML (DMLE) rescued HT22 mouse hippocampal neuronal cells from glutamate (Glu)-induced oxidative cell death; however, the protective compounds and mechanisms remain unknown. Here, we aimed to identify the neuroprotective ingredients and mechanisms of DMLE in the Glu-HT22 cell model. Five antioxidant compounds were isolated from DMLE and characterized as chlorogenic acid, hyperoside, isoquercitrin, quercetin, and rutin by spectroscopic methods. Isoquercitrin and quercetin significantly inhibited Glu-induced oxidative cell death by restoring intracellular reactive oxygen species (ROS) levels and mitochondrial superoxide generation, Ca2+ dysregulation, mitochondrial dysfunction, and nuclear translocation of apoptosis-inducing factor. These two compounds significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the presence or absence of Glu treatment. Combinatorial treatment of the five compounds based on the equivalent concentrations in DMLE showed that significant protection was found only in the cells cotreated with isoquercitrin and quercetin, both of whom showed prominent synergism, as assessed by drug–drug interaction analysis. These findings suggest that isoquercitrin and quercetin are the active principles representing the protective effects of DMLE, and these effects were mediated by the Nrf2/HO-1 pathway.

scholarly journals Vascular Protective Role of Samul-Tang in HUVECs: Involvement of Nrf2/HO-1 and NO

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Eun Sik Choi ◽  
Yun Jung Lee ◽  
Chang Seob Seo ◽  
Jung Joo Yoon ◽  
Byung Hyuk Han ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Molecular Mechanisms ◽  
Water Extract ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Ros Production ◽  
Herbal Formula ◽  
Protective Effects ◽  
Monocyte Adhesion

Samul-Tang (Si-Wu-Tang, SMT), composed of four medicinal herbs, is a well-known herbal formula treating hematological disorder or gynecologic disease. However, vascular protective effects of SMT and its molecular mechanisms on the vascular endothelium, known as the central spot of vascular inflammatory process, are not reported. The aim of this study was to investigate vascular protective effects of SMT water extract in human umbilical vein endothelial cells (HUVECs). Water extract of SMT was prepared and identified by HPLC-PDA analysis. Expression of cell adhesion molecules (CAMs) and heme oxygenase-1 (HO-1) and translocation of nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined by western blot. Nuclear localization of NF-κB and Nrf2 was visualized by immunofluorescence and DNA binding activity of NF-κB was measured. ROS production, HL-60 monocyte adhesion, and intracellular nitric oxide (NO) were also measured using a fluorescent indicator. SMT suppressed NF-κB translocation and activation as well as expression of CAMs, monocyte adhesion, and ROS production induced by TNF-αin HUVECs. SMT treated HUVECs showed upregulation of HO-1 and NO which are responsible for vascular protective action. Our study suggests that SMT, a traditionally used herbal formula, protects the vascular endothelium from inflammation and might be used as a promising vascular protective drug.

l-carnitine protects human hepatocytes from oxidative stress-induced toxicity through Akt-mediated activation of Nrf2 signaling pathway

2016 ◽  
Vol 94 (5) ◽  
pp. 517-525 ◽  
Author(s):  
Jinlian Li ◽  
Yanli Zhang ◽  
Haiyun Luan ◽  
Xuehong Chen ◽  
Yantao Han ◽  
...  
Keyword(s):  
Protective Effect ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Cell Damage ◽  
Binding Activity ◽  
Akt Pathway ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Akt Inhibitor ◽  
Nrf2 Signaling Pathway

In our previous study, l-carnitine was shown to have cytoprotective effect against hydrogen peroxide (H2O2)-induced injury in human normal HL7702 hepatocytes. The aim of this study was to investigate whether the protective effect of l-carnitine was associated with the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) pathway. Our results showed that pretreatment with l-carnitine augmented Nrf2 nuclear translocation, DNA binding activity and heme oxygenase-1 (HO-1) expression in H2O2-treated HL7702 cells, although l-carnitine treatment alone had no effect on them. Analysis using Nrf2 siRNA demonstrated that Nrf2 activation was involved in l-carnitine-induced HO-1 expression. In addition, l-carnitine-mediated protection against H2O2 toxicity was abrogated by Nrf2 siRNA, indicating the important role of Nrf2 in l-carnitine-induced cytoprotection. Further experiments revealed that l-carnitine pretreatment enhanced the phosphorylation of Akt in H2O2-treated cells. Blocking Akt pathway with inhibitor partly abrogated the protective effect of l-carnitine. Moreover, our finding demonstrated that the induction of Nrf2 translocation and HO-1 expression by l-carnitine directly correlated with the Akt pathway because Akt inhibitor showed inhibitory effects on the Nrf2 translocation and HO-1 expression. Altogether, these results demonstrate that l-carnitine protects HL7702 cells against H2O2-induced cell damage through Akt-mediated activation of Nrf2 signaling pathway.

scholarly journals Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1805
Author(s):  
Chan-Min Liu ◽  
Zhi-Kai Tian ◽  
Yu-Jia Zhang ◽  
Qing-Lei Ming ◽  
Jie-Qiong Ma ◽  
...  
Keyword(s):  
Phenolic Glycoside ◽  
Related Factor ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Nrf2 Pathway ◽  
Wnt Inhibitor ◽  
Research Findings ◽  
Anti Oxidant ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibited potential neuroprotective properties. Here we examined the protective effects of GAS against lead(Pb)-induced nerve injury in mice, and explores its underlying mechanisms. Our research findings revealed that GAS improved behavioral deficits in Pb-exposed mice. GAS reduced the accumulation of p-tau and amyloid-beta (Aβ). GAS inhibited Pb-induced inflammation in the brain, as indicated by the decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-α), cyclooxygenase-2 (COX-2). GAS increased the expression levels of NR2A and neurotrophin brain-derived neurotrophic factor (BDNF). GAS inhibited Pb-induced apoptosis of neurons in hippocampus tissue, as indicated by the decreased levels of pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the neuroprotective effects of GAS were associated with inhibiting oxidative stress by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling. GAS supplement activated the Wnt/β-catenin signaling pathway and reduced the expression of Wnt inhibitor Dickkopf-1 (Dkk-1). Collectively, this study clarified that GAS exhibited neuroprotective property by anti-oxidant, anti-inflammatory and anti-apoptosis effects and its ability to regulate the Wnt/Nrf2 pathway.

scholarly journals Tripterine up-regulates miR-223 to alleviate lipopolysaccharide-induced damage in murine chondrogenic ATDC5 cells

2019 ◽  
Vol 33 ◽  
pp. 205873841882452 ◽  
Author(s):  
Xuefu Li ◽  
Wei Wei ◽  
Zhongquan Zhao ◽  
Shuzhen Lv
Keyword(s):  
Western Blot ◽  
Therapeutic Potential ◽  
Cell Damage ◽  
Quantitative Polymerase Chain Reaction ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inhibitory Effects ◽  
Tnf Α ◽  
Associated Proteins ◽  
Regulatory Effects ◽  
Induced Apoptosis

Tripterine, also known as celastrol, is a main natural ingredient in Tripterygium wilfordii. Tripterine has a variety of pharmacological functions, and the therapeutic potential of tripterine in many kinds of inflammation-linked diseases has been revealed. However, the function of tripterine on osteoarthritis still remains unclear. The objective of this study was to study the function of tripterine (TPR) on lipopolysaccharide (LPS)-injured chondrocyte. ATDC5 cells were treated with tripterine after LPS stimulation and then cell survival, the release of pro-inflammatory cytokines, and the expression of chondrogenic differentiation-associated proteins were assessed by performing CCK-8, flow cytometry, reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and Western blot. Moreover, the expression of miR-223 and core factors in PI3K/AKT and nuclear factor kappa B (NF-κB) signaling was tested by RT-qPCR/Western blot. LPS stimulation significantly reduced ATDC5 cells viability, induced apoptosis, and increased the release of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Tripterine protected ATDC5 cells against LPS-induced chondrocyte loss and the release of IL-6 and TNF-α. miR-223 was down-regulated by LPS, while was up-regulated by tripterine. The protective actions of tripterine were eliminated when miR-223 was silenced. Besides, tripterine inhibited hypertrophic differentiation induced by LPS, and the inhibitory effects of tripterine on hypertrophic differentiation could be abolished when miR-223 was silenced. Furthermore, tripterine activated PI3K/AKT pathway and deactivated NF-κB pathway. And the regulatory effects of tripterine on these two pathways were abolished by miR-223 silence. This study revealed that tripterine protected ATDC5 cells against LPS-induced cell damage possibly via up-regulation of miR-223 and modulation of NF-κB and PI3K/AKT pathways.

scholarly journals CSIG-20. EFFECT OF TUMOR-TREATING FIELDS (TTFIELDS) ON EGFR PHOSPHORYLATION IN GBM CELL LINES

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi48-vi48
Author(s):  
Maria Luisa D’Angelo ◽  
Deborah Piffaretti ◽  
Floriana Burgio ◽  
Alessio Chiappini ◽  
Francesco Marchi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Protoporphyrin Ix ◽  
Growth Factor Receptor ◽  
Iron Chelator ◽  
Heme Oxygenase 1 ◽  
Tumor Treating Fields ◽  
Epidermal Growth ◽  
Tin Protoporphyrin ◽  
Novel Strategy ◽  
Rate Limiting

Abstract Glioblastoma (GBM) is the most common high grade and most devastating brain tumor among adults. About 50% of GBM express EGFR (epidermal growth factor receptor) and from these another 50% the mutated form EGFRvIII which is associated with a more aggressive disease and poorer prognosis. We have previously shown that expression of different status of EGFR in GBM cell lines drives the 5-ALA induced fluorescence downstream by influencing the rate-limiting enzyme heme oxygenase-1 (HO-1) probably via PI3K/Akt signalling. We demonstrated that 5-ALA-induced protoporphyrin IX (PpIX) fluorescence is pharmacologically influenced by adding different drugs such as deferoxamine (DFO) and tin-protoporphyrin (SnPP), which are an iron chelator of Fe2+ and an inhibitor of HO-1 respectively, or genistein that promotes PpIX accumulation via functional repression of ABCG2 (ABC transporter G2). Our aim is to increase these pharmacological effects on PpIX fluorescence using tumor-treating fields (TTFields). TTFields, a new therapeutic technology for treating newly diagnosed or recurrent GBM, is able to suppress the growth of cancer cells destabilising microtubule elongation and increasing membrane permeability. Interestingly, TTFields, like as other destabilising drugs and compounds, is able to inhibit the phosphorylation of EGFR and subsequent downregulation of EGFR-induced signalling acting for example on the mechanism that regulate the HO-1 activity. Here, we investigate the effects of TTFields on glioma cells, with different EGFR status and consequently different PpIX fluorescence. Exposure to TTFields during or after pharmacological treatments may represent a novel strategy to block or diminish the phosphorylation of EGFR to ameliorate the visualization of PpIX fluorescence in patients where it is not enough to ensure a safe and precise removal of the tumor bulk. In fact, if a combination of TTFields and drug treatment should give the desired results, this strategy could be applied on patients before being subjected to surgical resection.

scholarly journals Oregano Essential Oil Induces SOD1 and GSH Expression through Nrf2 Activation and Alleviates Hydrogen Peroxide-Induced Oxidative Damage in IPEC-J2 Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Yi Zou ◽  
Jun Wang ◽  
Jian Peng ◽  
Hongkui Wei
Keyword(s):  
Hydrogen Peroxide ◽  
Essential Oil ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Cell Damage ◽  
Antioxidant Response ◽  
Related Factor ◽  
Protective Effects ◽  
Oregano Essential Oil ◽  
Protein Levels

Oregano essential oil (OEO) has long been used to improve the health of animals, particularly their intestinal health. The health benefits of OEO are generally attributed to antioxidative actions, but the mechanisms remain unclear. Here, we investigate the antioxidative effects of OEO and their underlying molecular mechanisms in porcine small intestinal epithelial (IPEC-J2) cells. We found that OEO treatment prior to hydrogen peroxide (H2O2) exposure increased cell viability and prevented lactate dehydrogenase (LDH) release into the medium. H2O2-induced reactive oxygen species (ROS) and malondialdehyde (MDA) were remarkably suppressed by OEO. OEO dose-dependently increased mRNA and protein levels of the nuclear factor-erythroid 2-related factor-2 (Nrf2) target genes Cu/Zn-superoxide dismutase (SOD1) and g-glutamylcysteine ligase (GCLC, GLCM), as well as intracellular concentrations of SOD1 and glutathione. OEO also increased intranuclear expression of Nrf2 and the activity of an antioxidant response element reporter plasmid in IPEC-J2 cells. The OEO-induced expression of Nrf2-regulated genes and increased SOD1 and glutathione concentrations in IPEC-J2 cells were reduced by Nrf2 small interfering (si) RNAs, counteracting the protective effects of OEO against oxidative stress in IPEC-J2 cells. Our results suggest that OEO protects against H2O2-induced IPEC-J2 cell damage by inducing Nrf2 and related antioxidant enzymes.

scholarly journals Protective effects of upregulated HO-1 gene against the apoptosis of human retinal pigment epithelial cells in vitro

2021 ◽  
Vol 14 (5) ◽  
pp. 649-655
Author(s):  
Yu Hong ◽  
◽  
Wei-Qi Chen ◽  
Liu-Xia You ◽  
Qing-Feng Ni ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Lentiviral Vector ◽  
Retinal Pigment ◽  
B Cell Lymphoma ◽  
Retinal Pigment Epithelial Cells ◽  
Cell Counting ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects

AIM: To investigate the protective effect of heme oxygenase-1 (HO-1) against H2O2-induced apoptosis in human ARPE-19 cells. METHODS: The lentiviral vector expressing HO-1 was prepared and transfected into apoptotic ARPE-19 cells induced by H2O2. Functional experiments including cell counting kit-8 (CCK-8) assay, flow cytometry (FCM) and mitochondrial membrane potential assay were conducted. RESULTS: The ultrastructure of ARPE-19 cells was observed using transmission electron microscope (TEM). It was found that exogenous HO-1 significantly ameliorated H2O2-induced loss of cell viability, apoptosis and intracellular levels of reactive oxygen species (ROS) in ARPE-19 cells. The overexpression of HO-1 facilitated the transfer of nuclear factor erythroid-2-related factor 2 (Nrf2) from cytoplasm to nucleus, which in turn upregualted expressions HO-1 and B-cell lymphoma-2 (Bcl-2). Furthermore, HO-1 upregulation further inhibited H2O2-induced release of cysteinyl aspartate specific proteinase-3 (caspase-3). CONCLUSION: Exogenous HO-1 protect ARPE-19 cells against H2O2-induced oxidative stress by regulating the expressions of Nrf2, HO-1, Bcl-2, and caspase-3.

scholarly journals GLP-1(9-36), a GLP-1 cleavage product, protects against oxidative stress and apoptosis through PI3K/Akt/NOS pathway in H9c2 cardiomyoblasts

2021 ◽  
Author(s):  
Narawat Nuamnaichati ◽  
Warisara Parichatikanond ◽  
Supachoke Mangmool
Keyword(s):  
Oxidative Stress ◽  
Active Form ◽  
Heme Oxygenase 1 ◽  
No Production ◽  
Protective Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Akt Phosphorylation ◽  
H9c2 Cardiomyoblasts ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Abstract GLP-1(7–36), a major active form of GLP-1 hormone, is rapidly cleaved by dipeptidyl peptidase-4 to generate a truncated metabolite, GLP-1(9–36) which has a low affinity for GLP-1 receptor (GLP-1R). GLP-1(7–36) has been shown to have protective effects on cardiovascular system through GLP-1R-dependent way. Nevertheless, the cardioprotective effects of GLP-1(9–36) have not fully understood. The present study investigated the effects of GLP-1(9–36), including its underlying mechanisms against oxidative stress and apoptosis in H9c2 cardiomyoblasts. Here, we reported that GLP-1(9–36) protects H9c2 cardiomyoblasts from hydrogen peroxide (H2O2)-induced oxidative stress by promoting the synthesis of antioxidant enzymes, glutathione peroxidase-1, catalase, and heme oxygenase-1. In addition, treatment with GLP-1(9–36) suppressed H2O2-induced apoptosis by attenuating caspase-3 activity and upregulating proapoptotic proteins, Bcl-2 and Bcl-xL. These protective effects of GLP-1(9–36) are attenuated by blockade of PI3K-mediated Akt phosphorylation and prevention of nitric oxide synthase (NOS)-induced NO production. Collectively, GLP-1(9–36) represents the potential therapeutic target for prevention of oxidative stress and apoptosis in the heart.

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