scholarly journals Protective Effects of 6,7,4′-Trihydroxyflavanone on Hypoxia-Induced Neurotoxicity by Enhancement of HO-1 through Nrf2 Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 341 ◽  
Author(s):  
Hyun-Su Lee ◽  
Gil-Saeng Jeong
Keyword(s):  
Signaling Pathway ◽  
Neurodegenerative Disorders ◽  
Nuclear Translocation ◽  
Protoporphyrin Ix ◽  
Protective Role ◽  
Osteoclast Formation ◽  
Protective Effects ◽  
Protein Levels ◽  
Nrf2 Signaling Pathway ◽  
Pre Treatment

Since hypoxia-induced neurotoxicity is one of the major causes of neurodegenerative disorders, including the Alzheimer’s disease, continuous efforts to find a novel antioxidant from natural products are required for public health. 6,7,4′-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been shown to inhibit osteoclast formation and have an antibacterial activity. However, no evidence has reported whether THF has a protective role against hypoxia-induced neurotoxicity. In this study, we found that THF is not cytotoxic, but pre-treatment with THF has a cytoprotective effect on CoCl2-induced hypoxia by restoring the expression of anti-apoptotic proteins in SH-SY5y cells. In addition, pre-treatment with THF suppressed CoCl2-induced hypoxia-related genes including HIF1α, p53, VEGF, and GLUT1 at the mRNA and protein levels. Pre-treatment with THF also attenuated the oxidative stress occurred by CoCl2-induced hypoxia by preserving antioxidant proteins, including SOD and CAT. We revealed that treatment with THF promotes HO-1 expression through Nrf2 nuclear translocation. An inhibitor assay using tin protoporphyrin IX (SnPP) confirmed that the enhancement of HO-1 by pre-treatment with THF protects SH-SY5y cells from CoCl2-induced neurotoxicity under hypoxic conditions. Our results demonstrate the advantageous effects of THF against hypoxia-induced neurotoxicity through the HO-1/Nrf2 signaling pathway and provide a therapeutic insight for neurodegenerative disorders.

Astaxanthin and Nrf2 signaling pathway: a novel target for new therapeutic approaches

2021 ◽  
Vol 21 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Zahra Ahmadi ◽  
Habib Yaribeygi ◽  
Thozhukat Sathyapalan ◽  
Amirhossein Sahebkar
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Haematococcus Pluvialis ◽  
Primary Source ◽  
Redox Balance ◽  
Protective Effects ◽  
Beneficial Effects ◽  
New Therapeutic Approaches ◽  
Nrf2 Signaling Pathway

: Astaxanthin (AST) is a naturally occurring compound isolated from various sources such as fungi, plants, salmon, and crab. However, Haematococcus Pluvialis, a green alga, is the primary source of this beta carotenoid compound. AST has several favourable biological and pharmacological activities such as antioxidant, anti-inflammatory, anti-tumor, anti-diabetes, hepatoprotective and neuroprotective. Nevertheless, the exact molecular mechanisms of these protective effects of AST are unclear yet. The Nrf2 signaling pathway is one of the critical candidate signaling pathways that may be involved in these beneficial effects of AST. This signaling pathway is responsible for maintaining the redox balance in the physiologic state. Upon nuclear translocation, Nrf2 signaling activates antioxidant enzymes to reduce oxidative stress and protect cells against damage. In the current study, we have reviewed the effects of AST on the Nrf2 signaling pathway, which could potentially be developed as a novel therapeutic approach for the management of various diseases.

scholarly journals Luteolin Alleviates AflatoxinB1-Induced Apoptosis and Oxidative Stress in the Liver of Mice through Activation of Nrf2 Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1268
Author(s):  
Shahid Ali Rajput ◽  
Aftab Shaukat ◽  
Kuntan Wu ◽  
Imran Rashid Rajput ◽  
Dost Muhammad Baloch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Aflatoxin B1 ◽  
Physiological Saline ◽  
Protective Effects ◽  
Biochemical Alterations ◽  
Protein Levels ◽  
Nrf2 Signaling Pathway ◽  
Induced Apoptosis

Aflatoxin B1 (AFB1), a threatening mycotoxin, usually provokes oxidative stress and causes hepatotoxicity in animals and humans. Luteolin (LUTN), well-known as an active phytochemical agent, acts as a strong antioxidant. This research was designed to investigate whether LUTN exerts protective effects against AFB1-induced hepatotoxicity and explore the possible molecular mechanism in mice. A total of forty-eight mice were randomly allocated following four treatment groups (n = 12): Group 1, physiological saline (CON). Group 2, treated with 0.75 mg/kg BW aflatoxin B1 (AFB1). Group 3, treated with 50 mg/kg BW luteolin (LUTN), and Group 4, treated with 0.75 mg/kg BW aflatoxin B1 + 50 mg/kg BW luteolin (AFB1 + LUTN). Our findings revealed that LUTN treatment significantly alleviated growth retardation and rescued liver injury by relieving the pathological and serum biochemical alterations (ALT, AST, ALP, and GGT) under AFB1 exposure. LUTN ameliorated AFB1-induced oxidative stress by scavenging ROS and MDA accumulation and boosting the capacity of the antioxidant enzyme (CAT, T-SOD, GSH-Px and T-AOC). Moreover, LUTN treatment considerably attenuates the AFB1-induced apoptosis in mouse liver, as demonstrated by declined apoptotic cells percentage, decreased Bax, Cyt-c, caspase-3 and caspase-9 transcription and protein with increased Bcl-2 expression. Notably, administration of LUTN up-regulated the Nrf2 and its associated downstream molecules (HO-1, NQO1, GCLC, SOD1) at mRNA and protein levels under AFB1 exposure. Our results indicated that LUTN effectively alleviated AFB1-induced liver injury, and the underlying mechanisms were associated with the activation of the Nrf2 signaling pathway. Taken together, LUTN may serve as a potential mitigator against AFB1-induced liver injury and could be helpful for the development of novel treatment to combat liver diseases in humans and/or animals.

scholarly journals Curcumin Protects Human Trophoblast HTR8/SVneo Cells from H2O2-Induced Oxidative Stress by Activating Nrf2 Signaling Pathway

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 121 ◽  
Author(s):  
Lina Qi ◽  
Jingle Jiang ◽  
Jingfei Zhang ◽  
Lili Zhang ◽  
Tian Wang
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Signaling Pathway ◽  
Protective Effects ◽  
Human Trophoblast ◽  
Nrf2 Signaling Pathway ◽  
Antioxidant Proteins ◽  
Pre Treatment ◽  
Induced Apoptosis ◽  
Excessive Accumulation

Pregnancy complications are associated with oxidative stress induced by accumulation of trophoblastic ROS in the placenta. We employed the human trophoblast HTR8/SVneo cell line to determine the effect of curcumin pre-treatment on H2O2-induced oxidative damage in HTR8/Sveo cells. Cells were pretreated with 2.5 or 5 μM curcumin for 24 h, and then incubated with 400 μM H2O2 for another 24 h. The results showed that H2O2 decreased the cell viability and induced excessive accumulation of reactive oxygen species (ROS) in HTR8/Sveo cells. Curcumin pre-treatment effectively protected HTR8/SVneo cells against oxidative stress-induced apoptosis via increasing Bcl-2/Bax ratio and decreasing the protein expression level of cleaved-caspase 3. Moreover, curcumin pre-treatment alleviated the excessive oxidative stress by enhancing the activity of antioxidative enzymes. The antioxidant effect of curcumin was achieved by activating Nrf2 and its downstream antioxidant proteins. In addition, knockdown of Nrf2 by Nrf2-siRNA transfection abolished the protective effects of curcumin on HTR8/SVneo cells against oxidative damage. Taken together, our results show that curcumin could protect HTR8/SVneo cells from H2O2-induced oxidative stress by activating Nrf2 signaling pathway.

scholarly journals Pentamethylquercetin Attenuates Cardiac Remodeling via Activation of the Sestrins/Keap1/Nrf2 Pathway in MSG-Induced Obese Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Jingxia Du ◽  
Wei He ◽  
Cai Zhang ◽  
Jianzhao Wu ◽  
Zhi Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cardiac Remodeling ◽  
Metabolic Disorders ◽  
Cardiac Fibrosis ◽  
Nuclear Translocation ◽  
Monosodium Glutamate ◽  
Immunofluorescent Staining ◽  
Obese Mice ◽  
Nrf2 Signaling Pathway ◽  
Obesity Cardiomyopathy

Objective. Obesity causes a variety of metabolic alterations that may contribute to abnormalities of the cardiac structure and function (obesity cardiomyopathy). In previous works, we have shown that pentamethylquercetin (PMQ) significantly improved metabolic disorders in obese mice and it inhibited pressure overload-induced cardiac remodeling in mice. However, its potential benefit in obesity cardiomyopathy remains unclear. The aim of this study was to investigate the effects of PMQ on cardiac remodeling in obese mice. Methods. We generated a monosodium glutamate-induced obese (MSG-IO) model in mice, which were treated with PMQ (5, 10, and 20 mg/kg) for 16 weeks consecutively. We examined the metabolic parameters and observed cardiac remodeling by performing cardiac echocardiography and Masson’s staining. The expression levels of molecules associated with the endogenous antioxidant system, including the sestrins/kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, were analyzed by western blotting and immunofluorescent staining. Results. We found that PMQ treatment significantly ameliorated obesity phenotypes and improved metabolic disorders in MSG-IO mice. PMQ decreased the heart wall thickness and attenuated cardiac fibrosis. Further study revealed that the protective effects of PMQ might be mediated by promoting Keap1 degradation and augmenting sestrins expression and Nrf2 nuclear translocation. Conclusion. Our findings indicated that PMQ ameliorated cardiac remodeling in obese mice by targeting the sestrins/Keap1/Nrf2 signaling pathway.

scholarly journals Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinale against Acetaminophen-Induced Liver Injury in Mice via Regulation of the Nrf2-Keap1 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Guosheng Lin ◽  
Dandan Luo ◽  
Jingjing Liu ◽  
Xiaoli Wu ◽  
Jinfen Chen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Hepatoprotective Effect ◽  
Dendrobium Officinale ◽  
Regulatory Subunit ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Glutamate Cysteine Ligase ◽  
Nrf2 Signaling Pathway

The effect of polysaccharides isolated from Dendrobium officinale (DOP) on acetaminophen- (APAP-) induced hepatotoxicity and the underlying mechanisms involved are investigated. Male Institute of Cancer Research (ICR) mice were randomly assigned to six groups: (1) control, (2) vehicle (APAP, 230 mg/kg), (3) N-acetylcysteine (100 mg/kg), (4) 50 mg/kg DOP, (5) 100 mg/kg DOP, and (6) 200 mg/kg DOP. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum and glutathione (GSH), malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (T-AOC), myeloperoxidase (MPO), and reactive oxygen species (ROS) levels in the liver were determined after the death of the mice. The histological examination of the liver was also performed. The effect of DOP on the Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was evaluated using Western blot analysis and real-time polymerase chain reaction (PCR). The results showed that DOP treatment significantly alleviated the hepatic injury. The decrease in ALT and AST levels in the serum and ROS, MDA, and MPO contents in the liver, as well as the increases in GSH, CAT, and T-AOC in the liver, were observed after DOP treatment. DOP treatment significantly induced the dissociation of Nrf2 from the Nrf2−Keap1 complex and promoted the Nrf2 nuclear translocation. Subsequently, DOP-mediated Nrf2 activation triggered the transcription and expressions of the glutamate–cysteine ligase catalytic (GCLC) subunit, glutamate–cysteine ligase regulatory subunit (GCLM), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1) in APAP-treated mice. The present study revealed that DOP treatment exerted potentially hepatoprotective effects against APAP-induced liver injury. Further investigation about mechanisms indicated that DOP exerted the hepatoprotective effect by suppressing the oxidative stress and activating the Nrf2−Keap1 signaling pathway.

scholarly journals Salvianolic Acid B Improves Postresuscitation Myocardial and Cerebral Outcomes in a Murine Model of Cardiac Arrest: Involvement of Nrf2 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Qing-Qi Ji ◽  
Yan-Jie Li ◽  
Ying-Hua Wang ◽  
Zi Wang ◽  
Liang Fang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Signaling Pathway ◽  
Murine Model ◽  
Nuclear Translocation ◽  
Salvia Miltiorrhiza ◽  
Left Ventricular ◽  
Salvianolic Acid B ◽  
Mitochondrial Morphology ◽  
Salvianolic Acid ◽  
Nrf2 Signaling Pathway

Survival and outcome of cardiac arrest (CA) are dismal despite improvements in cardiopulmonary resuscitation (CPR). Salvianolic acid B (Sal B), extracted from Salvia miltiorrhiza, has been investigated for its cardioprotective properties in cardiac remodeling and ischemic heart disease, but less is known about its role in CA. The aim of this study was to learn whether Sal B improves cardiac and neurologic outcomes after CA/CPR in mice. Female C57BL/6 mice were subjected to eight minutes of CA induced by an intravenous injection of potassium chloride (KCl), followed by CPR. After 30 seconds of CPR, mice were blindly randomized to receive either Sal B (20 mg/kg) or vehicle (normal saline) intravenously. Hemodynamic variables and indices of left ventricular function were determined before CA and within three hours after CPR, the early postresuscitation period. Sal B administration resulted in a remarkable decrease in the time required for the return of spontaneous circulation (ROSC) in animals that successfully resuscitated compared to the vehicle-treated mice. Myocardial performance, including cardiac output and left ventricular systolic (dp/dtmax) and diastolic (dp/dtmin) function, was clearly ameliorated within three hours of ROSC in the Sal B-treated mice. Moreover, Sal B inhibited CA/CPR-induced cardiomyocyte apoptosis and preserved mitochondrial morphology and function. Mechanistically, Sal B dramatically promoted Nrf2 nuclear translocation through the downregulation of Keap1, which resulted in the expression of antioxidant enzymes, including HO-1 and NQO1, thereby counteracted the oxidative damage in response to CA/CPR. The aforementioned antiapoptotic and antioxidant effects of Sal B were impaired in the setting of gene silencing of Nrf2 with siRNA in vitro model. These improvements were associated with better neurological function and increased survival rate (75% vs. 40%, p<0.05) up to 72 hours postresuscitation. Our findings suggest that the administration of Sal B improved cardiac function and neurological outcomes in a murine model of CA via activating the Nrf2 antioxidant signaling pathway, which may represent a novel therapeutic strategy for the treatment of CA.

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 Protective Effects of Rice Peptide Oryza Peptide-P60 against Oxidative Injury through Activation of Nrf2 Signaling Pathway In Vitro and In Vivo

ACS Omega ◽  
2020 ◽  
Vol 5 (22) ◽  
pp. 13096-13107
Author(s):  
Chie Moritani ◽  
Kayoko Kawakami ◽  
Hiroshi Shimoda ◽  
Tadashi Hatanaka ◽  
Etsuko Suzaki ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Oxidative Injury ◽  
Protective Effects ◽  
Nrf2 Signaling Pathway

scholarly journals miR-135b Plays a Neuroprotective Role by Targeting GSK3β in MPP+-Intoxicated SH-SY5Y Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jianlei Zhang ◽  
Wei Liu ◽  
Yabo Wang ◽  
Shengnan Zhao ◽  
Na Chang
Keyword(s):  
Cell Proliferation ◽  
Glycogen Synthase ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Protective Effects ◽  
Inflammatory Cytokine Production ◽  
Protein Levels

miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson’s disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3β (GSK3β) was upregulated at mRNA and protein levels in MPP+-intoxicated SH-SY5Y cells in a dose- and time-dependent manner. MTT, TUNEL, and ELISA assays revealed that miR-135b overexpression significantly promoted cell proliferation and inhibited apoptosis and production of TNF-α and IL-1β in SH-SY5Y cells in the presence of MPP+. Luciferase reporter assay demonstrated that GSK3β was a direct target of miR-135b. Moreover, sodium nitroprusside (SNP), a GSK3β activator, dramatically reversed the effects of miR-135b upregulation on cell proliferation, apoptosis, and inflammatory cytokine production in MPP+-intoxicated SH-SY5Y cells. Taken together, miR-135b exerts a protective role via promotion of proliferation and suppression of apoptosis and neuroinflammation by targeting GSK3β in MPP+-intoxicated SH-SY5Y cells, providing a potential therapeutic target for the treatment of PD.

scholarly journals Effects of chitooligosaccharide-zinc on mice ovarian function in premature ovarian failure via regulating the sestrin2/nrf2 signaling pathway

2020 ◽  
Author(s):  
Jia Li ◽  
Yuhang Chen ◽  
Jiayu Xu ◽  
Jiangying Liu ◽  
Jiacheng Fu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ovarian Function ◽  
Treated Group ◽  
Control Group ◽  
Chitosan Oligosaccharide ◽  
Protective Effects ◽  
Developmental Defects ◽  
Adult Mice ◽  
Nrf2 Signaling Pathway ◽  
Significant Difference

Abstract BackgroundThe chitosan oligosaccharide-zinc (COS·Zn) is also a powerful antioxidant and anti-aging scavenger, whose anti-oxidative ability immensely exceeds that of vitamin C. Therefore, this study aimed to investigate the protective effects and potential mechanism by which COS·Zn improves ovarian function and delays aging in POF.MethodsThe female KM adult mice and POF mice were divided into treated and prevention groups; these were prophylactically or therapeutically administered COS·Zn (150mg/kg·d, 300mg/kg·d) for 21 days, respectively. ResultsThe number of antral follicles in COS·Zn-treated groups was lower in the treated and prevention groups than that in the control group, respectively. Obviously, the ovarian index, the level of FSH and LH all increased notably during the 300 mg/kg·d treated group and the prevention group compared with cy/bus groups. The expression of MVH, OCT4 and PCNA in the 300 mg/kg·d treated groups and MVH in the prevention groups were remarkably increased compared with the CY/BUS group. Meanwhile, the protein levels of P53 and P16 were markedly down-regulated in the treated groups and prevention groups compared with CY/BUS, except for the expression of P53 in the prevention groups. Furthermore, the Sestrin2 (SESN2) and SOD2 proteins were significantly higher in the 150 mg/kg·d treated group compared with the CY/BUS group, but the 300 mg/kg·d and CY/BUS group showed no significant difference in the level of SESN2. Similarly, the NRF2 and SESN2 proteins were up-regulated in the prevention groups, and the change in SOD2 was not significant. The results revealed increased GSH levels in the 150 mg/kg·d and 300 mg/kg·d treated groups compared with CY/BUS group, and the same trend was also shown in the prevention groups.1Conclusion COS·Zn improves ovarian and follicular developmental defects caused by regulating the sestrin2-nrf2 signaling pathway, and these results suggest a novel product that is effective a POF prevention and treatment drug.

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