scholarly journals Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the Akt/GSK-3β/Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 5/6 Nephrectomized Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Hong-feng Zhang ◽  
Jia-hong Wang ◽  
Yan-li Wang ◽  
Cheng Gao ◽  
Yan-ting Gu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Dependent Manner ◽  
Salvianolic Acid ◽  
Nrf2 Signaling Pathway ◽  
Antioxidative Effects ◽  
Dose Dependent

Salvianolic acid A (SAA) is a bioactive polyphenol extracted from Salviae miltiorrhizae Bunge, which possesses a variety of pharmacological activities. In our previous study, we have demonstrated that SAA effectively attenuates kidney injury and inflammation in an established animal model of 5/6 nephrectomized (5/6Nx) rats. However, there has been limited research regarding the antioxidative effects of SAA on chronic kidney disease (CKD). Here, we examined the antioxidative effects and underlying mechanisms of SAA in 5/6Nx rats. The rats were injected with SAA (2.5, 5, and 10 mg·kg-1·d-1, ip) for 28 days. Biochemical, flow cytometry, and Western blot analyses showed that SAA significantly increased the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GPx), and catalase (CAT) and lowered the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and NADPH oxidase 4 (NOX-4) in a dose-dependent manner in 5/6Nx rats and in H2O2-induced HK-2 cells in vitro. Moreover, SAA enhanced the activation of the protein kinase B/glycogen synthase kinase-3β/nuclear factor-erythroid-2-related factor 2 (Akt/GSK-3β/Nrf2) signaling pathway in a dose-dependent manner and subsequently increased the expression of heme oxygenase-1 (HO-1) in the kidney of 5/6Nx rats, which were consistent with those obtained in H2O2-induced HK-2 cells in vitro shown by Western blot analysis. Furthermore, SAA significantly increased the expression of intranuclear Nrf2 and HO-1 proteins compared to HK-2 cells stimulated by LPS on the one hand, which can be enhanced by QNZ to some extent; on the other hand, SAA significantly lowered the expression of p-NF-κB p65 and ICAM-1 proteins compared to HK-2 cells stimulated by H2O2, which can be abrogated by ML385 to some extent. In conclusion, our results demonstrated that SAA effectively protects the kidney against oxidative stress in 5/6Nx rats. One of the pivotal mechanisms for the protective effects of SAA on kidney injury was mainly related with its antioxidative roles by activating the Akt/GSK-3β/Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway.

scholarly journals Ganoderic Acid D Protects Human Amniotic Mesenchymal Stem Cells against Oxidative Stress-Induced Senescence through the PERK/NRF2 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Yan Xu ◽  
Huan Yuan ◽  
Yi Luo ◽  
Yu-Jie Zhao ◽  
Jian-Hui Xiao
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Signaling Pathway ◽  
Adult Stem Cells ◽  
Telomerase Activity ◽  
Related Factor ◽  
Dependent Manner ◽  
Ganoderic Acid ◽  
Nrf2 Signaling Pathway

Aging is an important risk factor in the occurrence of many chronic diseases. Senescence and exhaustion of adult stem cells are considered as a hallmark of aging in organisms. In this study, a senescent human amniotic mesenchymal stem cell (hAMSC) model subjected to oxidative stress was established in vitro using hydrogen peroxide. We investigated the effects of ganoderic acid D (GA-D), a natural triterpenoid compound produced from Ganoderma lucidum, on hAMSC senescence. GA-D significantly inhibited β-galactosidase (a senescence-associated marker) formation, in a dose-dependent manner, with doses ranging from 0.1 μM to 10 μM, without inducing cytotoxic side-effects. Furthermore, GA-D markedly inhibited the generation of reactive oxygen species (ROS) and the expression of p21 and p16 proteins, relieved the cell cycle arrest, and enhanced telomerase activity in senescent hAMSCs. Furthermore, GA-D upregulated the expression of phosphorylated protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK), peroxidase III (PRDX3), and nuclear factor-erythroid 2-related factor (NRF2) and promoted intranuclear transfer of NRF2 in senescent cells. The PERK inhibitor GSK2656157 and/or the NRF2 inhibitor ML385 suppressed the PERK/NRF2 signaling, which was activated by GA-D. They induced a rebound for the generation of ROS and β-galactosidase-positive cells and attenuated the differentiation capacity. These findings suggest that GA-D retards hAMSC senescence through activation of the PERK/NRF2 signaling pathway and may be a promising candidate for the discovery of antiaging agents.

scholarly journals Sulforaphane induces colorectal cancer cell proliferation through Nrf2 activation in a p53-dependent manner

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Yunjeong Gwon ◽  
Jisun Oh ◽  
Jong-Sang Kim
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Related Factor ◽  
Mild Stress ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Nrf2 Signaling Pathway ◽  
Dose Dependent

AbstractSulforaphane is a well-known phytochemical that stimulates nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant cellular response. In this study, we found that sulforaphane promoted cell proliferation in HCT116 human colon cancer cells expressing a normal p53 gene in a dose-dependent but biphasic manner. Since p53 has been reported to contribute to cell survival by regulating various metabolic pathways to adapt to mild stress, we further examined cellular responses in both p53-wild-type (WT) and p53-knockout (KO) HCT116 cells exposed to sulforaphane in vitro and in vivo. Results demonstrated that sulforaphane treatment activated Nrf2-mediated antioxidant enzymes in both p53-WT and p53-KO cells, decreased apoptotic protein expression in WT cells but increased in KO cells in a dose-dependent manner, and increased the expression of a mitochondrial biogenesis marker PGC1α in WT cells but decreased in KO cells. Moreover, a low dose of sulforaphane promoted tumor growth, upregulated the Nrf2 signaling pathway, and decreased apoptotic cell death in p53-WT HCT116 xenografts compared to that in p53-KO HCT116 xenografts in BALB/c nude mice. These findings suggest that sulforaphane can influence colon cancer cell proliferation and mitochondrial function through a crosstalk between the Nrf2 signaling pathway and p53 axis.

scholarly journals Melatonin Promotes In Vitro Maturation of Vitrified-Warmed Mouse Germinal Vesicle Oocytes, Potentially by Reducing Oxidative Stress through the Nrf2 Pathway

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2324
Author(s):  
Shichao Guo ◽  
Jinyu Yang ◽  
Jianpeng Qin ◽  
Izhar Hyder Qazi ◽  
Bo Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
In Vitro Maturation ◽  
Germinal Vesicle ◽  
Melatonin Receptors ◽  
Development Rates ◽  
Nrf2 Signaling Pathway ◽  
Mouse Gv Oocytes ◽  
Intracellular Oxidative Stress

Previously it was reported that melatonin could mitigate oxidative stress caused by oocyte cryopreservation; however, the underlying molecular mechanisms which cause this remain unclear. The objective was to explore whether melatonin could reduce oxidative stress during in vitro maturation of vitrified-warmed mouse germinal vesicle (GV) oocytes through the Nrf2 signaling pathway or its receptors. During in vitro maturation of vitrified-warmed mouse GV oocytes, there were decreases (p < 0.05) in the development rates of metaphase I (MI) oocytes and metaphase II (MII) and spindle morphology grades; increases (p < 0.05) in the reactive oxygen species (ROS) levels; and decreases (p < 0.05) in expressions of Nrf2 signaling pathway-related genes (Nrf2, SOD1) and proteins (Nrf2, HO-1). However, adding 10−7 mol/L melatonin to both the warming solution and maturation solutions improved (p < 0.05) these indicators. When the Nrf2 protein was specifically inhibited by Brusatol, melatonin did not increase development rates, spindle morphology grades, genes, or protein expressions, nor did it reduce vitrification-induced intracellular oxidative stress in GV oocytes during in vitro maturation. In addition, when melatonin receptors were inhibited by luzindole, the ability of melatonin to scavenge intracellular ROS was decreased, and the expressions of genes (Nrf2, SOD1) and proteins (Nrf2, HO-1) were not restored to control levels. Therefore, we concluded that 10−7 mol/L melatonin acted on the Nrf2 signaling pathway through its receptors to regulate the expression of genes (Nrf2, SOD1) and proteins (Nrf2, HO-1), and mitigate intracellular oxidative stress, thereby enhancing in vitro development of vitrified-warmed mouse GV oocytes.

Effect of fluoride on PERK-Nrf2 signaling pathway in mouse ameloblasts

2019 ◽  
Vol 38 (7) ◽  
pp. 833-845
Author(s):  
X Zhou ◽  
Z Chen ◽  
W Zhong ◽  
R Yu ◽  
L He
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Signaling Pathway ◽  
Nuclear Import ◽  
Target Genes ◽  
Dental Fluorosis ◽  
Related Factor ◽  
Dependent Manner ◽  
Nrf2 Signaling Pathway ◽  
Glutamylcysteine Synthetase

In the development of dental fluorosis, oxidative stress is considered as the key mechanism. Endoplasmic reticulum (ER) stress can induce oxidative stress and activate the important antioxidative factor nuclear factor erythroid 2-related factor 2 (Nrf2) in a PKR-like ER kinase (PERK)-dependent manner, but combining ER stress and oxidative stress, the role of PERK-Nrf2 signaling pathway involved in fluoride-regulated ameloblasts is not fully defined. Here, we studied the effect of fluoride on PERK-Nrf2 signaling pathway in mouse ameloblasts. We found that low-dose and continuous fluoride exposure increased binding immunoglobulin protein expression and activated PERK–activating transcription factor 4 signaling pathway. Meanwhile, the expression of Nrf2 and its target genes (glutamylcysteine synthetase and glutathione S-transferase-P1) enhanced following ER stress. Tunicamycin increased the expression of PERK, leading to Nrf2 nuclear import, and tauroursodeoxycholate suppressed Nrf2 activation through PERK during ER stress, indicating that PERK activation is required for Nrf2 nuclear entry. Furthermore, tert-butylhydroquinone triggered the overexpression of Nrf2 to reduce ER stress, but luteolin inhibited Nrf2 nuclear localization to elevate ER stress. In summary, this study proved that fluoride under certain dose can induce ER stress and promote Nrf2 nuclear import via PERK activation and suggested that antioxidation mechanism mediated by PERK-Nrf2 can alleviate fluoride-induced ER stress effectively.

scholarly journals Damaging Effects of Bisphenol A on the Kidney and the Protection by Melatonin: Emerging Evidences from In Vivo and In Vitro Studies

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Anongporn Kobroob ◽  
Wachirasek Peerapanyasut ◽  
Nipon Chattipakorn ◽  
Orawan Wongmekiat
Keyword(s):  
Oxidative Stress ◽  
Bisphenol A ◽  
Mitochondrial Function ◽  
Dependent Manner ◽  
Redox Equilibrium ◽  
Membrane Potential Change ◽  
Kidney Mitochondria ◽  
Dose Dependent

This study investigates the effects of bisphenol A (BPA) contamination on the kidney and the possible protection by melatonin in experimental rats and isolated mitochondrial models. Rats exposed to BPA (50, 100, and 150 mg/kg, i.p.) for 5 weeks demonstrated renal damages as evident by increased serum urea and creatinine and decreased creatinine clearance, together with the presence of proteinuria and glomerular injuries in a dose-dependent manner. These changes were associated with increased lipid peroxidation and decreased antioxidant glutathione and superoxide dismutase. Mitochondrial dysfunction was also evident as indicated by increased reactive oxygen species production, decreased membrane potential change, and mitochondrial swelling. Coadministration of melatonin resulted in the reversal of all the changes caused by BPA. Studies using isolated mitochondria showed that BPA incubation produced dose-dependent impairment in mitochondrial function. Preincubation with melatonin was able to sustain mitochondrial function and architecture and decreases oxidative stress upon exposure to BPA. The findings indicated that BPA is capable of acting directly on the kidney mitochondria, causing mitochondrial oxidative stress, dysfunction, and subsequently, leading to whole organ damage. Emerging evidence further suggests the protective benefits of melatonin against BPA nephrotoxicity, which may be mediated, in part, by its ability to diminish oxidative stress and maintain redox equilibrium within the mitochondria.

scholarly journals Macrophages-Derived, LRG1-Enriched Extracellular Vesicles Exacerbate Aristolochic Acid Nephropathy Via A TGFβR1-Dependent Manner

2021 ◽  
Author(s):  
Wenjuan Jiang ◽  
Jiahui Dong ◽  
Changlin Du ◽  
Chuanting Xu ◽  
Songbing Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aristolochic Acid ◽  
Herbal Medicines ◽  
Kidney Injury ◽  
Dependent Manner ◽  
Aristolochic Acid Nephropathy ◽  
Injury Model ◽  
Culture Model

Abstract Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by some herbal medicines, but treatment remains ineffective. We previously found NADPH oxidases 4 (NOX4), which regulates oxidative stress, play an important role in kidney injury model. However, its regulatory mechanism of action in AAN is still obscure. In this study, we established AAN model in vivo, a co-culture system of macrophage and TEC, and macrophage/TEC conditioned media culture model in vitro respectively. We found macrophages infiltration promoted injury，oxidative stress and apoptosis of TEC. Furthermore, the role of macrophage in AAN was dependent on macrophages-derived EV. Importantly, we found that macrophages-derived, Leucine-rich α-2-glycoprotein 1(LRG1)-enriched EV induced TEC injury and apoptosis of via a TGFβR1-dependent process. Mechanistically, macrophages-derived, LRG1-enriched EV mediating TECs injury by upregulating NOX4 in AAN model. This study may help design a better therapeutic strategy to treat AAN patients.

scholarly journals Fucoxanthin Pretreatment Ameliorates Visible Light-Induced Phagocytosis Disruption of RPE Cells under a Lipid-Rich Environment via the Nrf2 Pathway

Marine Drugs ◽  
2021 ◽  
Vol 20 (1) ◽  
pp. 15
Author(s):  
Yunjun Liu ◽  
Zixin Guo ◽  
Shengnan Wang ◽  
Yixiang Liu ◽  
Ying Wei
Keyword(s):  
Oxidative Stress ◽  
Visible Light ◽  
Signaling Pathway ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Rpe Cells ◽  
Retinal Injury ◽  
Nrf2 Signaling Pathway ◽  
Ameliorative Effect

Fucoxanthin, a special xanthophyll derived from marine algae, has increasingly attracted attention due to its diverse biological functions. However, reports on its ocular benefits are still limited. In this work, the ameliorative effect of fucoxanthin on visible light and lipid peroxidation-induced phagocytosis disruption in retinal pigment epithelium (RPE) cells was investigated in vitro. Marked oxidative stress, inflammation, and phagocytosis disruption were evident in differentiated RPE cells following their exposure to visible light under a docosahexaenoic acid (DHA)-rich environment. Following pretreatment with fucoxanthin, however, the activated nuclear factor erythroid-derived-2-like 2 (Nrf2) signaling pathway was observed and, furthermore, when the fucoxanthin -pretreated RPE cells were irradiated with visible light, intracellular reactive oxygen species (ROS), malondialdehyde (MDA) levels and inflammation were obviously suppressed, while phagocytosis was significantly improved. However, following the addition of Nrf2 inhibitor ML385, the fucoxanthin exhibited no ameliorative effects on the oxidative stress, inflammation, and phagocytosis disruption in the RPE cells, thus indicating that the ameliorative effect of fucoxanthin on the phagocytosis of RPE cells is closely related to the Nrf2 signaling pathway. In conclusion, these results suggest that fucoxanthin supplementation might be beneficial to the prevention of visible light-induced retinal injury.

scholarly journals Zinc is essential for the transcription function of the PGC-1α/Nrf2 signaling pathway in human primary endometrial stromal cells

2020 ◽  
Vol 318 (3) ◽  
pp. C640-C648 ◽  
Author(s):  
Xiaodan Lu ◽  
Qiang Zhang ◽  
Li Xu ◽  
Xiuying Lin ◽  
Jianhua Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Stromal Cells ◽  
Receptor Interaction ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Stem Cell Markers ◽  
Endometrial Stromal Cells ◽  
Nrf2 Signaling Pathway

Zinc (Zn) has antioxidant effect in different types of organs and is closely associated with human health. Endometrial receptivity is one of the most important factors in the embryo implantation and development. However, the regulatory mechanism of Zn in endometrium tissue is still unclear. In the study, we found that plasma Zn level is significantly associated with female infertility, which severely affects female reproductive health. Primary endometrial stromal cells were isolated from female endometrium and cultured in the laboratory. Zn chelator TPEN treatment reduced the expression of stem cell markers CD73, CD90, and CD105 and generated reactive oxygen species in endometrial stromal cells. However, pretreatment of Zn (zinc sulfate) is able to prevent TPEN-induced oxidative stress in vitro. By transcriptional profiling and gene ontology analysis, we found that Zn increased the cellular pluripotency signaling and extracellular matrix-receptor interaction, but reduced autophagy, endocytosis, and the nitrogen metabolism pathway. We further discovered the antioxidant function of Zn through the peroxisome proliferator-activated receptor gamma coactivator 1α/nuclear factor erythroid-2-related factor signaling pathway in endometrial stromal cells. Zn supplementation may open up an effective therapeutic approach for patients with oxidative stress-related endometrial diseases.

Protective effect of chloroform extract of Stereospermum chelonoides bark against amyloid beta42 induced cell death in SH-SY5Y cells and against inflammation in Swiss albino mice

2018 ◽  
Vol 29 (6) ◽  
pp. 621-630
Author(s):  
Md. Imamul Islam ◽  
Meena Afroze Shanta ◽  
Milon Mondal ◽  
Nazia Hoque ◽  
Senjuti Majumder ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Protective Effect ◽  
Antioxidant Capacity ◽  
Caspase 3 ◽  
Radical Scavenging ◽  
Chloroform Extract ◽  
Dependent Manner ◽  
Dose Dependent

Abstract Background This study was designed to evaluate the free radical scavenging property of chloroform extract of the bark of Stereospermum chelonoides (SCBC) and to investigate its potential in Alzheimer’s disease and inflammation, two oxidative stress related disorders. Methods Preliminary phytochemical analysis and in vitro antioxidant potential of SCBC were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, ferric reducing antioxidant power (FRAP) assay, cupric reducing antioxidant capacity (CUPRAC) and total antioxidant capacity determination assay. Total phenol and total flavonoid contents were also determined. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based cytotoxicity and cyto-protective assays were performed on human neuroblastoma SH-SY5Y cells. Thioflavin-T assay and caspase activation measurement assay were carried out to elucidate the mechanism of cytoprotection of SCBC observed here. In vivo anti-inflammatory potential was measured using croton oil and xylene induced ear edema tests. Results Phytochemical screening of SCBC revealed the presence of various phytoconstituents. Dose-dependent in vitro antioxidant activity was observed. The extract was enriched in flavonoids and polyphenolic compounds too. SCBC was found to inhibit amyloid-β peptide 1-42 (Aβ42) induced cell death in a dose-dependent manner. Encouraged by the cyto-protective effect, its effects on Aβ42 fibrillogenesis and caspase-3 activated apoptosis were observed. SCBC significantly slowed down the Aβ42 fibrillogenesis and caspase-3 activation in a concentration-dependent manner indicating its probable mechanism of rendering cyto-protection. SCBC has been able to reduce inflammation significantly in croton oil induced ear edema in both doses. Conclusions Thus, this study could form the basis for further study for the potential use of SCBC in oxidative stress associated cell death and inflammation.

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