scholarly journals Proanthocyanidins against Oxidative Stress: From Molecular Mechanisms to Clinical Applications

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Lingyu Yang ◽  
Dehai Xian ◽  
Xia Xiong ◽  
Rui Lai ◽  
Jing Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Low Cost ◽  
Natural Agents ◽  
Molecular Damage ◽  
And Control

Proanthocyanidins (PCs) are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerousin vitroandin vivostudies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, anti-inflammation, immunomodulation, DNA repair, and antitumor activity. Accumulation of prooxidants such as reactive oxygen species (ROS) exceeding cellular antioxidant capacity results in oxidative stress (OS), which can damage macromolecules (DNA, lipids, and proteins), organelles (membranes and mitochondria), and whole tissues. OS is implicated in the pathogenesis and exacerbation of many cardiovascular, neurodegenerative, dermatological, and metabolic diseases, both through direct molecular damage and secondary activation of stress-associated signaling pathways. PCs are promising natural agents to safely prevent acute damage and control chronic diseases at relatively low cost. In this review, we summarize the molecules and signaling pathways involved in OS and the corresponding therapeutic mechanisms of PCs.

Targeting PPARalpha in Alzheimer's Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 345-354 ◽  
Author(s):  
Barbara D'Orio ◽  
Anna Fracassi ◽  
Maria Paola Cerù ◽  
Sandra Moreno
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Antioxidant Response ◽  
Peroxisome Proliferator ◽  
Prevailing Paradigm

Background: The molecular mechanisms underlying Alzheimer's disease (AD) are yet to be fully elucidated. The so-called “amyloid cascade hypothesis” has long been the prevailing paradigm for causation of disease, and is today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflammation and energy dysmetabolism. The peroxisome proliferator-activated receptors (PPARs) are expressed in the central nervous system (CNS) and regulate many physiological processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle. Among the three isotypes (α, β/δ, γ), PPARγ role is the most extensively studied, while information on α and β/δ are still scanty. However, recent in vitro and in vivo evidence point to PPARα as a promising therapeutic target in AD. Conclusion: This review provides an update on this topic, focussing on the effects of natural or synthetic agonists in modulating pathogenetic mechanisms at AD onset and during its progression. Ligandactivated PPARα inihibits amyloidogenic pathway, Tau hyperphosphorylation and neuroinflammation. Concomitantly, the receptor elicits an enzymatic antioxidant response to oxidative stress, ameliorates glucose and lipid dysmetabolism, and stimulates autophagy.

scholarly journals Enhancing the Nrf2 Antioxidant Signaling Provides Protection Against Trichloroethene-mediated Inflammation and Autoimmune Response

2020 ◽  
Vol 175 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Nivedita Banerjee ◽  
Hui Wang ◽  
Gangduo Wang ◽  
M Firoze Khan
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Autoimmune Response ◽  
Mediated Effects ◽  
Antioxidant Gene Expression ◽  
Responsive Element

Abstract Trichloroethene (trichloroethylene, TCE) and one of its reactive metabolites dichloroacetyl chloride (DCAC) are associated with the induction of autoimmunity in MRL+/+ mice. Although oxidative stress plays a major role in TCE-/DCAC-mediated autoimmunity, the underlying molecular mechanisms still need to be delineated. Nuclear factor (erythroid-derived 2)-like2 (Nrf2) is an oxidative stress-responsive transcription factor that binds to antioxidant responsive element (ARE) and provides protection by regulating cytoprotective and antioxidant gene expression. However, the potential of Nrf2 in the regulation of TCE-/DCAC-mediated autoimmunity is not known. This study thus focused on establishing the role of Nrf2 and consequent inflammatory responses in TCE-/DCAC-mediated autoimmunity. To achieve this, we pretreated Kupffer cells (KCs) or T cells with/without tert-butylhydroquinone (tBHQ) followed by treatment with DCAC. In both KCs and T cells, DCAC treatment significantly downregulated Nrf2 and HO-1 expression along with induction of Keap-1 and caspase-3, NF-κB (p65), TNF-α, and iNOS, whereas pretreatment of these cells with tBHQ attenuated these responses. The in vitro findings were further verified in vivo by treating female MRL+/+ mice with TCE along with/without sulforaphane. TCE exposure in mice also led to reduction in Nrf2 and HO-1 but increased phospho-NF-κB (p-p65) and iNOS along with increased anti-dsDNA antibodies. Interestingly, sulforaphane treatment led to amelioration of TCE-mediated effects, resulting in Nrf2 activation and reduction in inflammatory and autoimmune responses. Our results show that TCE/DCAC mediates an impairment in Nrf2 regulation. Attenuation of TCE-mediated autoimmunity via activation of Nrf2 supports that antioxidants sulforaphane/tBHQ could be potential therapeutic agents for autoimmune diseases.

scholarly journals Aloin Preconditioning Attenuates Hepatic Ischemia/Reperfusion Injury via Inhibiting TLR4/MyD88/NF-κB Signal Pathway In Vivo and In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yichao Du ◽  
Baolin Qian ◽  
Lin Gao ◽  
Peng Tan ◽  
Hao Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Liver Tissue ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Primary Hepatocytes ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Background. Aloin exerts considerable protective effects in various disease models, and its effect on hepatic ischemia-reperfusion (HIR) injury remains unknown. This research is aimed at conducting an in-depth investigation of the antioxidant, anti-inflammatory, and antiapoptosis effects of aloin in HIR injury and explain the underlying molecular mechanisms. Methods. In vivo, different concentrations of aloin were intraperitoneally injected 1 h before the establishment of the HIR model in male mice. The hepatic function, pathological status, oxidative stress, and inflammatory and apoptosis markers were measured. In vitro, aloin (AL, C21H22O9) or lipopolysaccharide (LPS) was added to a culture of mouse primary hepatocytes before it underwent hypoxia/reoxygenation (H/R), and the apoptosis in the mouse primary hepatocytes was analyzed. Results. We found that 20 mg/kg was the optimum concentration of aloin for mitigating I/R-induced liver tissue damage, characterized by decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Aloin pretreatment substantially suppressed the generation of hepatic malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and IL-6 and enhanced the hepatic superoxide dismutase (SOD) activities as well as glutathione (GSH) and IL-10 levels in the liver tissue of I/R mice; this indicated that aloin ameliorated I/R-induced liver damage by reducing the oxidative stress and inflammatory response. Moreover, aloin inhibited hepatocyte apoptosis and inflammatory response that was caused by the upregulated expression of Bcl-2, the downregulated expression of cleaved caspase3(C-caspase3), Bax, Toll-like receptor 4 (TLR4), FADD, MyD88, TRAF6, phosphorylated IKKα/β (p-IKKα/β), and phosphorylated nuclear factor κB p65 (p-NF-κB p65).

Food Derived Bioactive Peptides for Health Enhancement and Management of Some Chronic Diseases

2019 ◽  
pp. 1-11
Author(s):  
A. F. Ogori ◽  
A. T. Girgih ◽  
J. O. Abu ◽  
M. O. Eke
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Molecular Mechanisms ◽  
Bioactive Peptides ◽  
Food Sources ◽  
In Vivo Studies ◽  
Future Research ◽  
Target Cells

The bioactive peptides produced by enzymatic hydrolysis, acid hydrolysis and fermentation approach have been identified and used widely in research. These methods are important in enhancement or prevention and management of chronic diseases that are ravaging the world such as type -2-diabetes, hypertension, oxidative stress, cancer, and obesity. Sources of bioactive peptides have been established ranging from plant to animal and marine foods that have pharmacological effects; however these effects are dependent on target cells and peptides structure and conformations.  Plants such as hemp and animal source such as milk among others validate the findings of In vitro and In-vivo studies and the efficiency of these bioactive peptides in the management of certain chronic diseases. This article reviews the literature on bioactive peptides with concern on food sources, production and bioactive peptides application in enhancement of health and management of hypertension, diabetes and oxidative stress.  Future research efforts on bioactive peptides should be directed towards elucidating specific sequenced bioactive peptides and their molecular mechanisms, through In-vivo and In-vitro studies for specific health condition in human using nutrigenomics and peptideomic approaches.

scholarly journals Oxidative stress and ageing of the post-ovulatory oocyte

Reproduction ◽  
2013 ◽  
Vol 146 (6) ◽  
pp. R217-R227 ◽  
Author(s):  
Tessa Lord ◽  
R John Aitken
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Embryo Quality ◽  
Fertilization Rates ◽  
Molecular Events ◽  
Post Implantation ◽  
Potential Use

With extended periods of time following ovulation, the metaphase II stage oocyte experiences deterioration in quality referred to as post-ovulatory oocyte ageing. Post-ovulatory ageing occurs both in vivo and in vitro and has been associated with reduced fertilization rates, poor embryo quality, post-implantation errors and abnormalities in the offspring. Although the physiological consequences of post-ovulatory oocyte ageing have largely been established, the molecular mechanisms controlling this process are not well defined. This review analyses the relationships between biochemical changes exhibited by the ageing oocyte and the symptoms associated with the ageing phenotype. We also discuss molecular events that are potentially involved in orchestrating post-ovulatory ageing with a particular focus on the role of oxidative stress. We propose that oxidative stress may act as the initiator for a cascade of events that create the aged oocyte phenotype. Specifically, oxidative stress has the capacity to cause a decline in levels of critical cell cycle factors such as maturation-promoting factor, impair calcium homoeostasis, induce mitochondrial dysfunction and directly damage multiple intracellular components of the oocyte such as lipids, proteins and DNA. Finally, this review addresses current strategies for delaying post-ovulatory oocyte ageing with a particular focus on the potential use of compounds such as caffeine or selected antioxidants in the development of more refined media for the preservation of oocyte integrity during IVF procedures.

scholarly journals The Antioxidant Mechanisms Underlying the Aged Garlic Extract- and S-Allylcysteine-Induced Protection

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Ana L. Colín-González ◽  
Ricardo A. Santana ◽  
Carlos A. Silva-Islas ◽  
Maria E. Chánez-Cárdenas ◽  
Abel Santamaría ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Original Data ◽  
Garlic Extract ◽  
Protective Effects ◽  
Aged Garlic Extract ◽  
Antioxidant Mechanisms ◽  
Aged Garlic

Aged garlic extract (AGE) is an odorless garlic preparation containing S-allylcysteine (SAC) as its most abundant compound. A large number of studies have demonstrated the antioxidant activity of AGE and SAC in bothin vivo—in diverse experimental animal models associated to oxidative stress—andin vitroconditions—using several methods to scavenge reactive oxygen species or to induce oxidative damage. Derived from these experiments, the protective effects of AGE and SAC have been associated with the prevention or amelioration of oxidative stress. In this work, we reviewed different antioxidant mechanisms (scavenging of free radicals and prooxidant species, induction of antioxidant enzymes, activation of Nrf2 factor, inhibition of prooxidant enzymes, and chelating effects) involved in the protective actions of AGE and SAC, thereby emphasizing their potential use as therapeutic agents. In addition, we highlight the ability of SAC to activate Nrf2 factor—a master regulator of the cellular redox state. Here, we include original data showing the ability of SAC to activate Nrf2 factor in cerebral cortex. Therefore, we conclude that the therapeutic properties of these molecules comprise cellular and molecular mechanisms at different levels.

scholarly journals The Molecular Mechanisms of Hypoglycemic Properties and Safety Profiles of Swietenia Macrophylla Seeds Extract: A Review

2021 ◽  
Vol 9 (F) ◽  
pp. 370-388
Author(s):  
Ratih Dewi Yudhani ◽  
Dwi Aris Agung Nugrahaningsih ◽  
Eti Nurwening Sholikhah ◽  
Mustofa Mustofa
Keyword(s):  
Oxidative Stress ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Density Lipoprotein ◽  
Thiobarbituric Acid ◽  
In Vitro Cytotoxicity ◽  
Swietenia Macrophylla

BACKGROUND: Insulin resistance (IR) is known as the root cause of type 2 diabetes; hence, it is a substantial therapeutic target. Nowadays, studies have shifted the focus to natural ingredients that have been utilized as a traditional diabetes treatment, including Swietenia macrophylla. Accumulating evidence supports the hypoglycemic activities of S. macrophylla seeds extract, although its molecular mechanisms have yet to be well-established. AIM: This review focuses on the hypoglycemic molecular mechanisms of S. macrophylla seeds extract and its safety profiles. METHODS: An extensive search of the latest literature was conducted from four main databases (PubMed, Scopus, Science Direct, and Google Scholar) using several keywords: “swietenia macrophylla, seeds, and diabetes;” “swietenia macrophylla, seeds, and oxidative stress;” “swietenia macrophylla, seeds, and inflammation;” “swietenia macrophylla, seeds, and GLUT4;” and “swietenia macrophylla, seeds, and toxicities.” RESULTS: The hypoglycemic activities occur through modulating several pathways associated with IR and T2D pathogenesis. The seeds extract of S. macrophylla modulates oxidative stress by decreasing malondialdehyde (MDA), oxidized low-density lipoprotein, and thiobarbituric acid-reactive substances while increasing antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase). Another propose mechanism is the modulating of the inflammatory pathway by attenuating nuclear factor kappa β, tumor necrosis factor α, inducible nitric oxide synthase, and cyclooxygenase 2. Some studies have shown that the extract can also control phosphatidylinositol-3-kinase/ Akt (PI3K/Akt) pathway by inducing glucose transporter 4, while suppressing phosphoenolpyruvate carboxykinase. Moreover, in vitro cytotoxicity and in vivo toxicity studies supported the safety profile of S. macrophylla seeds extract with the LD50 higher than 2000 mg/kg. CONCLUSION: The potential of S. macrophylla seeds as antidiabetic candidate is supported by many studies that have documented their non-toxic and hypoglycemic effects, which involve several molecular pathways.

scholarly journals Food Derived Bioactive Peptides for Health Enhancement and Management of Some Chronic Diseases

2019 ◽  
pp. 1-11
Author(s):  
A. F. Ogori ◽  
A. T. Girgih ◽  
J. O. Abu ◽  
M. O. Eke
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Molecular Mechanisms ◽  
Bioactive Peptides ◽  
Food Sources ◽  
In Vivo Studies ◽  
Future Research ◽  
Target Cells

The bioactive peptides produced by enzymatic hydrolysis, acid hydrolysis and fermentation approach have been identified and used widely in research. These methods are important in enhancement or prevention and management of chronic diseases that are ravaging the world such as type -2-diabetes, hypertension, oxidative stress, cancer, and obesity. Sources of bioactive peptides have been established ranging from plant to animal and marine foods that have pharmacological effects; however these effects are dependent on target cells and peptides structure and conformations.  Plants such as hemp and animal source such as milk among others validate the findings of In vitro and In-vivo studies and the efficiency of these bioactive peptides in the management of certain chronic diseases. This article reviews the literature on bioactive peptides with concern on food sources, production and bioactive peptides application in enhancement of health and management of hypertension, diabetes and oxidative stress.  Future research efforts on bioactive peptides should be directed towards elucidating specific sequenced bioactive peptides and their molecular mechanisms, through In-vivo and In-vitro studies for specific health condition in human using nutrigenomics and peptideomic approaches.

scholarly journals Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Mariachiara Buccarelli ◽  
Quintino Giorgio D’Alessandris ◽  
Paola Matarrese ◽  
Cristiana Mollinari ◽  
Michele Signore ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Strong Increase ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species

Abstract Background Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults, characterized by a poor prognosis mainly due to recurrence and therapeutic resistance. It has been widely demonstrated that glioblastoma stem-like cells (GSCs), a subpopulation of tumor cells endowed with stem-like properties is responsible for tumor maintenance and progression. Moreover, it has been demonstrated that GSCs contribute to GBM-associated neovascularization processes, through different mechanisms including the transdifferentiation into GSC-derived endothelial cells (GdECs). Methods In order to identify druggable cancer-related pathways in GBM, we assessed the effect of a selection of 349 compounds on both GSCs and GdECs and we selected elesclomol (STA-4783) as the most effective agent in inducing cell death on both GSC and GdEC lines tested. Results Elesclomol has been already described to be a potent oxidative stress inducer. In depth investigation of the molecular mechanisms underlying GSC and GdEC response to elesclomol, confirmed that this compound induces a strong increase in mitochondrial reactive oxygen species (ROS) in both GSCs and GdECs ultimately leading to a non-apoptotic copper-dependent cell death. Moreover, combined in vitro treatment with elesclomol and the alkylating agent temozolomide (TMZ) enhanced the cytotoxicity compared to TMZ alone. Finally, we used our experimental model of mouse brain xenografts to test the combination of elesclomol and TMZ and confirmed their efficacy in vivo. Conclusions Our results support further evaluation of therapeutics targeting oxidative stress such as elesclomol with the aim of satisfying the high unmet medical need in the management of GBM.

scholarly journals Oridonin Promotes Apoptosis and Restrains the Viability and Migration of Bladder Cancer by Impeding TRPM7 Expression via the ERK and AKT Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xianping Che ◽  
Jiangtao Zhan ◽  
Fan Zhao ◽  
Zunhe Zhong ◽  
Mianchuan Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Akt Signaling ◽  
Bladder Cancer Cell Line ◽  
Anticancer Efficacy ◽  
T24 Cells

Background. Oridonin is a powerful anticancer compound found in Rabdosia rubescens. However, its potential impact on bladder cancer remains uninvestigated. In this work, we aimed to detect the anticancer effect of oridonin on bladder cancer and explore the molecular mechanisms involved. Methods. The anticancer activity of oridonin was assessed in vitro with a CCK8 assay, an annexin V-FITC apoptosis analysis, and colony formation and Transwell migration assays which were performed with the human bladder cancer cell line T24. Levels of apoptosis-related proteins, melastatin transient receptor potential channel 7 (TRPM7), and signaling molecules were examined in oridonin-treated T24 cells by western blotting or RT-PCR. Oridonin anticancer efficacy was further validated in vivo with a T24 xenograft mouse model. Results. Oridonin repressed the proliferative, colony-forming, and migratory capacities of T24 cells, triggered extensive apoptosis in vitro, and retarded tumor growth in vivo. Moreover, oridonin treatment significantly increased expression levels of p53 and cleaved caspase-3 and reduced expression of TRPM7, p-AKT, and p-ERK. Conclusion. Oridonin exhibited outstanding antiproliferative and antimigratory effects on bladder cancer, and these effects were at least partially associated with targeting of TRPM7 through inactivation of the ERK and AKT signaling pathways. These findings provide insight for the clinical application of oridonin in bladder cancer prevention.

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