Cellular Antioxidant Defense System Research Articles

Curcumin inhibits proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression

Curcumin can inhibit cell proliferation of breast cancer, but the mechanism for this inhibition remains unclear. Over-expression of Flap endonuclease 1 (Fen1), a DNA repair-specific nuclease, is involved in the development of breast cancer. Nrf2 is a master regulator of cellular antioxidant defense systems. Curcumin can induce the expression of Nrf2 in both non-breast cancer cells and breast cancer cells. However, whether curcumin-induced inhibition of breast cancer cell proliferation may involve Nrf2-mediated Fen1 expression is not yet understood. In this study, we demonstrated that curcumin inhibited Fen1-dependent proliferation of MCF-7 cells and significantly induced Nrf2 protein expression while inhibiting Fen1 protein expression. Curcumin could down-regulate Fen1 gene expression in a Nrf2-dependent manner. Further investigation revealed that curcumin could lead to Nrf2 translocation from the cytoplasm to the nucleus and decrease Fen1 promoter activity by decreasing the recruitment of Nrf2 to the Fen1 promoter. These data suggest that curcumin may inhibit the proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression, which may be a new mechanism of curcumin-induced tumor growth inhibition.

Respiratory Viral Infections and Subversion of Cellular Antioxidant Defenses.

Reactive oxygen species (ROS) formation is part of normal cellular aerobic metabolism, due to respiration and oxidation of nutrients in order to generate energy. Low levels of ROS are involved in cellular signaling and are well controlled by the cellular antioxidant defense system. Elevated levels of ROS generation due to pollutants, toxins and radiation exposure, as well as infections, are associated with oxidative stress causing cellular damage. Several respiratory viruses, including respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and influenza, induce increased ROS formation, both intracellularly and as a result of increased inflammatory cell recruitment at the site of infection. They also reduce antioxidant enzyme (AOE) levels and/or activity, leading to unbalanced oxidative-antioxidant status and subsequent oxidative cell damage. Expression of several AOE is controlled by the activation of the nuclear transcription factor NF-E2-related factor 2 (Nrf2), through binding to the antioxidant responsive element (ARE) present in the AOE gene promoters. While exposure to several pro-oxidant stimuli usually leads to Nrf2 activation and upregulation of AOE expression, respiratory viral infections are associated with inhibition of AOE expression/activity, which in the case of RSV and hMPV is associated with reduced Nrf2 nuclear localization, decreased cellular levels and reduced ARE-dependent gene transcription. Therefore, administration of antioxidant mimetics or Nrf2 inducers represents potential viable therapeutic approaches to viral-induced diseases, such as respiratory infections and other infections associated with decreased cellular antioxidant capacity.

Neurological effects of honey: current and future prospects.

Honey is the only insect-derived natural product with therapeutic, traditional, spiritual, nutritional, cosmetic, and industrial value. In addition to having excellent nutritional value, honey is a good source of physiologically active natural compounds, such as polyphenols. Unfortunately, there are very few current research projects investigating the nootropic and neuropharmacological effects of honey, and these are still in their early stages. Raw honey possesses nootropic effects, such as memory-enhancing effects, as well as neuropharmacological activities, such as anxiolytic, antinociceptive, anticonvulsant, and antidepressant activities. Research suggests that the polyphenol constituents of honey can quench biological reactive oxygen species and counter oxidative stress while restoring the cellular antioxidant defense system. Honey polyphenols are also directly involved in apoptotic activities while attenuating microglia-induced neuroinflammation. Honey polyphenols are useful in improving memory deficits and can act at the molecular level. Therefore, the ultimate biochemical impact of honey on specific neurodegenerative diseases, apoptosis, necrosis, neuroinflammation, synaptic plasticity, and behavior-modulating neural circuitry should be evaluated with appropriate mechanistic approaches using biochemical and molecular tools.

Role of Cathepsin G in the Degradation of Glyceraldehyde-3-Phosphate Dehydrogenase Triggered by 4-Hydroxy-2-Nonenal in U937 Cells

Degradation of oxidized or oxidatively modified proteins is an essential part of the cellular antioxidant defense system. 4-Hydroxy-2-nonenal (HNE), a major reactive aldehyde formed by lipid peroxidation, causes many types of cellular damage. HNE-modified proteins are degraded by the ubiquitin-proteasome pathway or the lysosomal pathway. However, our previous studies using U937 cells showed that HNE-modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is degraded by cathepsin G. In the present study, we examined whether GAPDH in U937 cells treated with HNE in culture is degraded similarly to that incubated with HNE and U937 cell extract. Treatment with HNE for 10 min in culture decreased GAPDH activity in a concentration dependent manner, but did not affect GAPDH degradation. The proteasome activities were not affected by HNE, but culturing with HNE decreased cathepsin G activity and protein level in a concentration dependent manner. These results suggest that HNE-induced oxidative stress leads to decreased cathepsin G activity and results in the loss of GAPDH degradation. Taken together, our findings indicate that cathepsin G has an important role in the degradation of oxidatively modified GAPDH in U937 cells.

Melatonin is effective in reducing stress-induced organ damage in Wistar albino rats

In the present study, we tried to investigate the effects of melatonin, a novel antioxidant and a potent free radical scavenger, in stress-induced cerebral, cerebellar, cardiac, and hepatic oxidative damage using microscopic and biochemical analysis. A total of 32 male Wistar albino rats were divided into control, stress, stress + saline, and stress + melatonin groups. The rats from the stress groups were exposed to high stress conditions of starvation, immobilization, and cold exposure. The rats from the stress + melatonin group received melatonin daily at 20 mg/kg body weight intraperitoneally for 7 days. At the end of the experiment, the brain, cerebellum, heart, and liver were rapidly removed. The main histopathological damage scores (MHDSs) of the stress and stress + saline groups were higher than those of control group for all of the organs. The MHDSs of melatonin-administered group were lower than those of stress and stress + saline groups. The main tissue superoxide dismutase activities of the stress + melatonin group were even higher than those of the control group in the cerebellum and liver, and main tissue catalase activities of the stress + melatonin group were even higher than those of control group in all of the organs. As a conclusion, we found melatonin very effective in reducing stress-induced organ damage by inhibiting lipid peroxidation and supporting the cellular antioxidant defense system.

베타아밀로이드로 유도된 신경소교세포 사멸에 대한 루테올린의 보호효과 연구

Objectives : The purpose of this study is to investigate neuroprotective effects and molecular mechanisms of luteolin against β -amyloid (Aβ 25-35)-induced oxidative cell death in BV-2 cells. Methods : The protective effects of luteolin against Aβ25-35-induced cytotoxicity and apoptotic cell death were determined by MTT dye reduction assay and TUNEL staining, respectively. The apoptotic cell death was further analyzed by measuring mitochondrial transmembrane potential and expression of pro- and/or anti-apoptotic proteins. To elucidate the molecular mechanisms underlying the protective effects of luteolin, intracellular accumulation of reactive oxygen species, oxidative damages, and expression of antioxidant enzymes were examined. Results : Luteolin pretreatment effectively attenuated Aβ 25-35-induced apoptotic cell death indices such as DNA fragmentation, dissipation of mitochondrial transmembrane potential, increased Bax/Bcl-2 ratio, and activation of c-Jun N-terminal kinase and caspase-3 in BV-2 cells. Furthermore, Aβ 25-35-induced intracellular formation of reactive oxygen species and subsequent oxidative damages such as lipid peroxidation and depletion of endogenous antioxidant glutathione were suppressed by luteolin treatment. The neuroprotective effects of luteolin might be mediated by up-regulation of cellular antioxidant defense system via up-regulation of γ -glutamylcysteine ligase, a rate-limiting enzyme in the glutathione biosynthesis and superoxide dismutase, an enzyme involved in dismutation of superoxide anion into oxygen and hydrogen peroxide. Conclusions : These findings suggest that luteolin has a potential to protect against Aβ 25-35-induced neuronal cell death and damages thereby exhibiting therapeutic utilization for the prevention and/or treatment of Alzheimer’s disease.

Atmospheric Pressure Room Temperature Plasma Jets Facilitate Oxidative and Nitrative Stress and Lead to Endoplasmic Reticulum Stress Dependent Apoptosis in HepG2 Cells

Atmospheric pressure room temperature plasma jets (APRTP-Js) that can emit a mixture of different active species have recently found entry in various medical applications. Apoptosis is a key event in APRTP-Js-induced cellular toxicity, but the exact biological mechanisms underlying remain elusive. Here, we explored the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in APRTP-Js-induced apoptosis using in vitro model of HepG2 cells. We found that APRTP-Js facilitated the accumulation of ROS and RNS in cells, which resulted in the compromised cellular antioxidant defense system, as evidenced by the inactivation of cellular antioxidants including glutathione (GSH), superoxide dismutase (SOD) and catalase. Nitrotyrosine and protein carbonyl content analysis indicated that APRTP-Js treatment caused nitrative and oxidative injury of cells. Meanwhile, intracellular calcium homeostasis was disturbed along with the alteration in the expressions of GRP78, CHOP and pro-caspase12. These effects accumulated and eventually culminated into the cellular dysfunction and endoplasmic reticulum stress (ER stress)-mediated apoptosis. The apoptosis could be markedly attenuated by N-acetylcysteine (NAC, a free radical scavenger), which confirmed the involvement of oxidative and nitrative stress in the process leading to HepG2 cell apoptosis by APRTP-Js treatment.

ROS: Redux and paradox in fatty liver disease

ROS: Redux and paradox in fatty liver disease

Safranal Treatment Improves Hyperglycemia, Hyperlipidemia and Oxidative Stress in Streptozotocin-Induced Diabetic Rats

Clinical research has confirmed the efficacy of several plant extracts in the modulation of oxidative stress associated with diabetes mellitus. Findings indicate that safranal has antioxidant properties. The aim of the present study was the evaluation of possible protective effects of safranal against oxidative damage in diabetic rats. In this study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, three safranal (0.25, 0.50, 0.75 mg/kg/day)-treated diabetic groups. Diabetes was induced by streptozotocin (STZ) in rats. STZ was injected intraperitoneally at a single dose of 60 mg/kg for diabetes induction. Safranal (intraperitoneal injection) was administered 3 days after STZ administration; these injections were continued to the end of the study (4 weeks). At the end of the 4-week period, blood was drawn for biochemical assays. In order to determine the changes of cellular antioxidant defense systems, antioxidant enzymes including glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT) activities were measured in serum. Moreover we also measured serum nitric oxide (NO) and serum malondialdehyde (MDA) levels, a marker of lipid peroxidation. STZ-induced diabetes caused an elevation (p < 0.001) of blood glucose, MDA, NO, total lipids, triglycerides and cholesterol, with reduction of GSH level and CAT and SOD activities. The results indicated that the significant elevation in the blood glucose, MDA, NO, total lipids, triglycerides, cholesterol and reduction of glutathione level and CAT and SOD activity were ameliorated in the safranal-treated diabetic groups compared with the untreated groups, in a dose dependent manner (p < 0.05, p<0.01, p < 0.001). These results suggest that safranal has antioxidant properties and improves chemically-induced diabetes and its complications by modulation of oxidative stress.

The transcription factor Nrf2 promotes survival by enhancing the expression of uncoupling protein 3 under conditions of oxidative stress

Uncoupling protein 3 (UCP3) is a member of the mitochondrial inner membrane carrier superfamily that modulates energy efficiency by catalyzing proton conductance and thus decreasing the production of superoxide anion. However, its role during oxidative stress and the underlying regulatory and molecular mechanisms remain poorly understood. We sought to investigate how UCP3 expression is regulated by oxidative stress and to evaluate the putative antioxidant role of this protein. H2O2 treatment increased UCP3 expression and the nuclear accumulation of the transcription factor Nrf2 in C2C12 and HL-1 cells. Nrf2 siRNA prevented H2O2-induced UCP3 expression, increasing oxidative stress and cell death. ChIP assays identified an antioxidant-response element (ARE) within the UCP3 promoter that bound Nrf2 after exposure to H2O2. Luciferase reporter experiments confirmed increased ARE activity in H2O2-treated HL-1 cells. Importantly, H2O2 increased the UCP3-mediated proton leak, suggesting a role for this protein in attenuating ROS-induced damage. Nrf2 nuclear accumulation and increased UCP3 protein were also detected in intact mouse heart subjected to a condition known to increase ROS generation. This is the first study to demonstrate that H2O2 augments UCP3 expression and it provides the first evidence of Nrf2 binding to the UCP3 promoter in response to oxidative challenge. These findings suggest that UCP3 functions as a member of the cellular antioxidant defense system that protects against oxidative stress in vivo. In conclusion, we have identified a novel regulatory process induced by an oxidative insult whereby the expression of the mitochondrial protein UCP3 is driven by the Nrf2 transcription factor, which decreases ROS production and prevents cell death.

Abstract 5374: Sulforaphane reactivates the expression of Nrf2 through CpGs demethylation in TRAMP C1 cells.

Abstract Prostate cancer is one of the most deadly malignancies among men in the United States. Recent evidence suggests epigenetic alteration is involved during the development and progression of prostate cancer. Previously we have demonstrated that Nrf2, a key regulator of cellular antioxidant defense systems, was epigenetically silenced in TRAMP prostate cancers, as well as tumorigenic TRAMP C1 cells. Sulforaphane (SFN), an isothiocyanate rich in cruciferous vegetables, has been shown to be a potent cancer prevention agent for years. The aim of this study is to investigate the potential of SFN to reactivate the expression of Nrf2 in TRAMP C1 cells via epigenetic modifications. Bisulfite genomic sequencing (BGS) showed that treatment of SFN resulted in demethylation of the first 5 CpGs in the promoter region of Nrf2 gene. Methylation DNA immunoprecipitation (MeDIP) analysis revealed that SFN significantly reduced the anti-mecyt antibody binding to the first 5 CpGs of the Nrf2 promoter, corresponding to the BGS results. Reversion of the methylation status was found to be associated with re-expression of Nrf2 and its downstream NQO-1 at the mRNA and protein levels. Further analysis showed that SFN treatment decreased the expression of DNA methyltransferases (DNMTs), particularly DNMT1 and DNMT3a. Though SFN treatment showed differential effects on the protein expression of various HDACs, it increased the global level of active chromatin marker acetyl-H3. Taken together, our study suggests that SFN may exert its chemoprevention effect through epigenetic regulation modification of Nrf2 gene with subsequent induction of its downstream anti-oxidative stress pathway. Citation Format: Chengyue Zhang, Zheng-Yuan Su, Tin Oo Khor, Ah-Ng Kong. Sulforaphane reactivates the expression of Nrf2 through CpGs demethylation in TRAMP C1 cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5374. doi:10.1158/1538-7445.AM2013-5374

Sulforaphane enhances Nrf2 expression in prostate cancer TRAMP C1 cells through epigenetic regulation

Growing evidence suggests epigenetic alteration is involved during the development and progression of prostate cancer. Previously, we found Nrf2, a key regulator of cellular antioxidant defense systems, was silenced through epigenetic mechanism during tumorigenesis in vivo TRAMP mice and in vitro TRAMP C1 cells. Sulforaphane (SFN) in cruciferous vegetable has been demonstrated to be a potent cancer prevention agent for years. The aim of this study is to investigate the potential of SFN to restore Nrf2 expression in TRAMP C1 cells through epigenetic modifications. Bisulfite genomic sequencing results indicated that SFN treatment led to demethylation of the first 5 CpGs in the promoter region of the Nrf2 gene in TRAMP C1 cells. Using methylation DNA immunoprecipitation (MeDIP) assay, SFN significantly reduced the ratio of anti-mecyt antibody binding to the Nrf2 promoter containing the first 5 CpGs. SFN increased mRNA and protein expressions of Nrf2 and Nrf2 downstream target gene NQO-1. In addition, SFN decreased the protein levels of DNMT1 and DNMT3a. SFN treatment also attenuated the protein expression levels of HDACs 1, 4, 5, and 7 while increased the level of active chromatin marker acetyl-Histone 3 (Ac-H3). SFN treatments also increased chromatin-immunoprecipitated DNA of Nrf2 gene promoter using anti-Ac-H3 antibody. Taken together, our current study shows that SFN regulates Nrf2's CpGs demethylation and reactivation in TRAMP C1 cells, suggesting SFN may exert its chemopreventive effect in part via epigenetic modifications of Nrf2 gene with subsequent induction of its downstream anti-oxidative stress pathway.

Responses of Noccaea caerulescens and Lupinus albus in trace elements-contaminated soils

Plants exposed to trace elements can suffer from oxidative stress, which is characterised by the accumulation of reactive oxygen species, alteration in the cellular antioxidant defence system and ultimately lipid peroxidation. We assessed the most-appropriate stress indexes to describe the response of two plant species, with different strategies for coping with trace elements (TEs), to particular contaminants. Noccaea caerulescens, a hyperaccumulator, and Lupinus albus, an excluder, were grown in three soils of differing pH: an acidic soil, a neutral soil (both contaminated mainly by Cu, Zn and As) and a control soil. Then, plant stress indicators were measured. As expected, N. caerulescens accumulated higher levels of Zn and Cd in shoots than L. albus, this effect being stronger in the acid soil, reflecting greater TE solubility in this soil. However, the shoot concentrations of Mn were higher in L. albus than in N. caerulescens, while the As concentration was similar in the two species. In L. albus, the phenolic content and lipid peroxidation were related with the Cu concentration, whereas the Zn and Cd concentrations in N. caerulescens were more closely related to glutathione content and lipid peroxidation. Interestingly, phytochelatins were only found in L. albus grown in polluted soils. Hence, the two species differed with respect to the TEs which provoked stress and the biochemical indicators of the stress, there being a close relationship between the accumulation of TEs and their associated stress indicators in the different plant organs.

Molecular mechanisms of hypolipidemic effects of curcumin

Recent evidence suggests potential benefits from phytochemicals and micronutrients in reducing the elevated oxidative and lipid-mediated stress associated with inflammation, obesity, and atherosclerosis. These compounds may either directly scavenge reactive oxygen or nitrogen species or they may modulate the activity of signal transduction enzymes leading to changes in the expression of antioxidant genes. Alternatively, they may reduce plasma lipid levels by modulating lipid metabolic genes in tissues and thus reduce indirectly lipid-mediated oxidative and endoplasmic reticulum stress through their hypolipidemic effect. Here we review the proposed molecular mechanisms by which curcumin, a polyphenol present in the rhizomes of turmeric (Curcuma longa) spice, influences oxidative and lipid-mediated stress in the vascular system. At the molecular level, mounting experimental evidence suggests that curcumin may act chemically as scavenger of free radicals and/or influences signal transduction (e.g., Akt, AMPK) and modulates the activity of specific transcription factors (e.g., FOXO1/3a, NRF2, SREBP1/2, CREB, CREBH, PPARγ, and LXRα) that regulate the expression of genes involved in free radicals scavenging (e.g., catalase, MnSOD, and heme oxygenase-1) and lipid homeostasis (e.g., aP2/FABP4, CD36, HMG-CoA reductase, and carnitine palmitoyltransferase-I (CPT-1)). At the cellular level, curcumin may induce a mild oxidative and lipid-metabolic stress leading to an adaptive cellular stress response by hormetic stimulation of these cellular antioxidant defense systems and lipid metabolic enzymes. The resulting lower oxidative and lipid-mediated stress may not only explain the beneficial effects of curcumin on inflammation, cardiovascular, and neurodegenerative disease, but may also contribute to the increase in maximum life-span observed in animal models.

Oxidative Stress in Cardiovascular Diseases and Obesity: Role of p66Shc and Protein Kinase C

Reactive oxygen species (ROS) are a byproduct of the normal metabolism of oxygen and have important roles in cell signalling and homeostasis. An imbalance between ROS production and the cellular antioxidant defence system leads to oxidative stress. Environmental factors and genetic interactions play key roles in oxidative stress mediated pathologies. In this paper, we focus on cardiovascular diseases and obesity, disorders strongly related to each other; in which oxidative stress plays a fundamental role. We provide evidence of the key role played by p66Shc protein and protein kinase C (PKC) in these pathologies by their intracellular regulation of redox balance and oxidative stress levels. Additionally, we discuss possible therapeutic strategies aimed at attenuating the oxidative damage in these diseases.

Carnosic acid attenuates lipopolysaccharide-induced liver injury in rats via fortifying cellular antioxidant defense system

The study investigated the protective effects of carnosic acid (CA), the principal constituent of rosemary, on lipopolysaccharide (LPS)-induced oxidative/nitrosative stress and hepatotoxicity in rats. CA was administered orally to rats at doses of 15, 30 and 60mg/kg body weight before LPS challenge (single intraperitoneal injection, 1mg/kg body weight). The results revealed that CA inhibited LPS-induced liver damage and disorder of lipid metabolism, which were mainly evidenced by decreased serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. CA also inhibited LPS-induced oxidative/nitrosative stress by decreasing lipid peroxidation, protein carbonylation, and serum levels of nitric oxide. Histopathological examination demonstrated that CA could improve pathological abnormalities and reduce the immigration of inflammatory cells in liver tissues with LPS challenge. Concurrently, CA potently inhibited the LPS-induced rise in serum levels of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6. CA supplementation markedly enhanced the body’s cellular antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and glutathione in serum and liver after the LPS challenge. In conclusion, the present study suggests that CA successfully and dose dependently attenuates LPS-induced hepatotoxicity possibly by preventing cytotoxic effects of oxygen free radicals, NO and cytokines.

Increased Oxidative Damage in Carriers of the Germline TP53 p.R337H Mutation

Germline mutations in TP53 are the underlying defect of Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome, autosomal dominant disorders characterized by predisposition to multiple early onset cancers. In Brazil, a variant form of LFS/LFL is commonly detected because of the high prevalence of a founder mutation at codon 337 in TP53 (p.R337H). The p53 protein exerts multiple roles in the regulation of oxidative metabolism and cellular anti-oxidant defense systems. Herein, we analyzed the redox parameters in blood samples from p.R337H mutation carriers (C, n = 17) and non-carriers (NC, n = 17). We identified a significant increase in erythrocyte GPx activity and in plasma carbonyl content,an indicator of protein oxidative damage, in mutation carriers compared to non-carriers (P = 0.048 and P = 0.035, respectively). Mutation carriers also showed a four-fold increase in plasma malondialdehyde levels, indicating increased lipid peroxidation (NC = 40.20±0.71, C = 160.5±0.88, P<0.0001). Finally, carriers showed increased total antioxidant status but a decrease in plasma ascorbic acid content. The observed imbalance could be associated with deregulated cell bioenergetics and/or with increased inflammatory stress, two effects that may result from loss of wild-type p53 function. These findings provide the first evidence that oxidative damage occurs in carriers of a germline TP53 mutation, and these may have important implications regarding our understanding of the mechanisms responsible for germline TP53 p.R337H mutation-associated carcinogenesis.

Identification of UV-protective Activators of Nuclear Factor Erythroid-derived 2-Related Factor 2 (Nrf2) by Combining a Chemical Library Screen with Computer-based Virtual Screening

Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a master regulator of cellular antioxidant defense systems, and activation of this transcription factor is a promising strategy for protection of skin and other organs from environmental insults. To identify efficient Nrf2 activators in keratinocytes, we combined a chemical library screen with computer-based virtual screening. Among 14 novel Nrf2 activators, the most potent compound, a nitrophenyl derivative of 2-chloro-5-nitro-N-phenyl-benzamide, was characterized with regard to its molecular mechanism of action. This compound induced the expression of cytoprotective genes in keratinocytes isolated from wild-type but not from Nrf2-deficient mice. Most importantly, it showed low toxicity and protected primary human keratinocytes from UVB-induced cell death. Therefore, it represents a potential lead compound for the development of drugs for skin protection under stress conditions. Our study demonstrates that chemical library screening combined with advanced computational similarity searching is a powerful strategy for identification of bioactive compounds, and it points toward an innovative therapeutic approach against UVB-induced skin damage.

Antioxidant Properties of Rajgira (Amaranthus paniculatus) Leaves and Potential Synergy in Chemoprevention

In recent years there has been a substantial increase in the use of functional foods for disease control. Fruits and vegetables produce phytochemicals such as flavonoids and antioxidants which can lower oxidative stress and reduce the risk of chronic ailments like cancer. The aim of the present study was to investigate the antioxidant capacity and the possible protective effects of Amaranthus paniculatus leaves on the antioxidant defense system in Ehrlich's ascites carcinoma (EAC) -treated mice. Oral administration of the leaf extract at different doses caused a significant decrease in tumor volume, viable cell count and tumor weight and elevated the life span of EAC bearing mice. It also showed an improved antioxidant potential as evidenced by a significant increase in the cellular antioxidant defense system such as catalase, superoxide dismutase and reduced glutathione and also significantly reduced the levels of TBARS. The levels of RBC, hemoglobin and lymphocyte count were altered in EAC bearing mice and were reverted back to near normal levels after the treatment with the leaf extracts. Their adequate content of total phenolics and flavonoids, DPPH scavenging activity which further suggests that the extracts exert a significant protection against oxidative stress conditions.

Neuroprotective Effects of Dehydroglyasperin C through Activation of Heme Oxygenase-1 in Mouse Hippocampal Cells

Licorice, the root of the Glycyrrhiza species ( Glycyrrhiza uralensis Fisher), is known to have antioxidant, anti-inflammatory, antiviral, and antitumor properties. The objective of this study is to explore the neuroprotective effect of dehydroglyasperin C (DGC) against glutamate-induced oxidative stress in mouse hippocampal HT22 cells. DGC significantly reduced cytotoxicity and reactive oxygen species (ROS) generation induced by glutamate in HT22 cells, whereas DGC did not restore glutathione depletion caused by glutamate. In addition, it was further investigated whether DGC affected the expression of heme oxygenase (HO)-1, one of the major cellular antioxidant defense systems, and it was found that DGC dose-dependently increased HO-1 expression. DGC-mediated cytoprotection of HT22 neuronal cells from glutamate insult was abrogated by either HO-1 inhibitor (Tin protoporphyrin, SnPP) or AKT inhibitor (LY294002). In conclusion, the present results demonstrate for the first time that DGC protects neuronal cells against glutamate-induced oxidative injury through the induction of HO-1 expression, which is, in turn, activated maybe through Nrf2-Keap1 and PI3K/AKT signaling pathways.