• Archives of Pharmacal Research
• /
• v.27 no.8
• /
• pp.867-872
• /
• 2004

Oxidative stress due to reactive oxygen species (ROS) can cause oxidative damage to cells. Cells have a number of defense mechanisms to protect themselves from the toxicity of ROS. Mitochondria are especially important in the oxidative stress as ROS have been found to be constantly generated as an endogen threat. Mitochondrial defense depends mainly on super-oxide dismutase (SOD) and glutathione peroxidase (GPx), whereas microsomal defense depends on catalase (CAT), which is an enzyme abundant in microsomes. SOD removes superoxide anions by converting them to $H_2O$$_2$, which can be rapidly converted to water by CAT and GPx. Also, GPx converts hydroperoxide (ROOH) into oxidized-glutathione (GSSG). Ovariectomized (OVX) rats are used as an oxidative stress model. An ovariectomy increased the levels of MDA, one of the end-products in the lipid peroxidative process, and decreased levels of the antioxidative enzymes； SOD, CAT and GPx. However, Chondroitin sulfate (CS) decreased the levels of MDA, but increased the levels of SOD, CAT and GPx in a dose-depen-dent manner. Moreover, inflammation and cirrhosis of liver tissue in CS- treated rats were sig-nificantly decreased. These results suggest that CS might be a potential candidate as an anti oxidative reagent.

• The Journal of Internal Korean Medicine
• /
• v.32 no.1
• /
• pp.56-67
• /
• 2011

Objectives : Recent etiological studies show that oxidative stress might play a major role in the diabetes and its complications. Mori Ramulus (MR) has been known to have antioxidative, anti-inflammatory and antidiabetic effects. The methanol extract of MR was tested for its effectiveness in LLC-PK1 cells exposed to high glucose. Methods : The cytoprotective effect of MR was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The antioxidative effect was measured in terms of generation amount of ${\cdot}O_2^-$ by 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), NO by 4,5-diaminofluorescein (DAF-2), $ONOO^-$ by dihydrorhodamine 123 (DHR 123) in the high glucose -treated LLC-$PK_1$ cells. Western blotting was performed using anti-AGE, anti-RAGE, anti-MAPKs(ERK1/2, JNK, p38), anti-PI3K, anti-Akt, and anti-NF-${\kappa}$B (p50, p65) respectively. Results : MR extract reduced cell death and inhibited the generation of ${\cdot}O_2^-$, NO, $ONOO^-$ in the high glucose-treated LLC-$PK_1$ cells. MR inhibited the expression of AGE, RAGE, MAPKs, PI3K, and Akt by means of decreasing NF-${\kappa}$B activation. MR also inhibited NF-${\kappa}$B activation itself. Conclusions : These results indicate MR has cytoprotective, antioxidative, and anti-inflammatory effects. Therefore it is suggested that MR might prevent and cure diabetes and its complications.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.23 no.5
• /
• pp.969-973
• /
• 2009

Samul-tang (SMT), which was firstly described in (Hwajegukbang) Song dynasty, is well known remedy for blood diseases in Oriental medicine. SMT is traditional herbal-remedy composed of Rehmanniae Radix Preparat, Angelicae Gigantis Radix, Cnidii Rhizoma and Paeoniae Radix. Recently, SMT has known to have anti-oxidative action. However, the reports on anti-oxidantic action in neuroglial cells are rare. In addition, the exact mechanisms are unclear. For these reasons, we investigated the protective effects of SMT on cell death induced by oxidative stress using C6 glioma cells. In our results, SMT accelerated proliferation rates of C6 cells in vitro. In addition, levels of LDH release induced by oxidative stress were lowered by treatment with SMT. Finally, protective effects on cell death induced by chemicals such as paraquat and rotenone were observed. In conclusion, these results suggest the possibility to protect brain cell or neuronal cell from damage induced by oxidative stress.

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.197.1-197.1
• /
• 2003

Neuronal hyperexcitability followed by high level of intracellular calcium and oxidative stress play critical roles in neuronal cell death in stroke and neurotrauma. Hence, KR-31378, a novel benzopyran derivative was designed as a new therapeutic strategy for neuroprotection possessing both anti-oxidant and potassium channel modulating activities. In the present study, we tested for its neuroprotective efficacy against oxidative stress-induced cell death in primary cortical cultures and further investigated its neuroprotective mechanism. (omitted)

• Journal of Ginseng Research
• /
• v.45 no.4
• /
• pp.473-481
• /
• 2021

Background: Mitochondrial dysfunction is one of the significant reasons for Alzheimer's disease (AD). Ginsenosides, natural molecules extracted from Panax ginseng, have been demonstrated to exert essential neuroprotective functions, which can ascribe to its anti-oxidative effect, enhancing central metabolism and improving mitochondrial function. However, a comprehensive analysis of cellular mitochondrial bioenergetics after ginsenoside treatment under Aβ-oxidative stress is missing. Methods: The antioxidant activities of ginsenoside Rb₁, Rd, Re, Rg₁ were compared by measuring the cell survival and reactive oxygen species (ROS) formation. Next, the protective effects of ginsenosides of mitochondrial bioenergetics were examined by measuring oxygen consumption rate (OCR) in PC12 cells under Aβ-oxidative stress with an extracellular flux analyzer. Meanwhile, mitochondrial membrane potential (MMP) and mitochondrial dynamics were evaluated by confocal laser scanning microscopy. Results: Ginsenoside Rg₁ possessed the strongest anti-oxidative property, and which therefore provided the best protective function to PC12 cells under the Aβ oxidative stress by increasing ATP production to 3 folds, spare capacity to 2 folds, maximal respiration to 2 folds and non-mitochondrial respiration to 1.5 folds, as compared to Aβ cell model. Furthermore, ginsenoside Rg1 enhanced MMP and mitochondrial interconnectivity, and simultaneously reduced mitochondrial circularity. Conclusion: In the present study, these results demonstrated that ginsenoside Rg₁ could be the best natural compound, as compared with other ginsenosides, by modulating the OCR of cultured PC12 cells during oxidative phosphorylation, in regulating MMP and in improving mitochondria dynamics under Aβ-induced oxidative stress.

• Journal of Life Science
• /
• v.19 no.4
• /
• pp.520-525
• /
• 2009

Early onset of Batten disease (EBD), one of the most lethal neurodegenerative storage disorders of childhood, is caused by inactivating mutations in the Ceroid Lipofuscinosis, Neuronal (CLN1) gene. Neurogranin, a calmodulin-binding protein, is expressed in the brain and participates in the protein kinase C (PKC) signaling pathway. While oxidative stress is the suggested cause of neurodegeneration in EBD, its molecular mechanism(s) remains obscure. In this research, we examined the levels of neurogranin in the brain mRNA of wild-type (WT) mice and EBD knockout (KO) mice, as well as the proteins. We also performed neuronal cultures to measure the expression levels of neurgranin and phosphorylated-neurogranin with or without oxidative stress inducers and anti-oxidants. Results showed that neurogranin in both EBD KO mice brain mRNA and protein extracts decreased in an age dependent manner. However, high amounts of phosphorylated-neurogranin were detected in the 6-month brain. This pattern was also confirmed by cultured neurospheres samples. Moreover, neurospheres treated with $H_2O_2$, an oxidative stress inducer, showed increased phosphorylated-neurogranin patterns. Interestingly, this pattern returned to normal status when treated with N-acetyl-L-cystein, an anti-oxidant, after $H_2O_2$ treatment was performed. Our results suggest that the phosphorylation of neurogranin is affected by oxidative stress status in EBD, and appropriate anti-oxidant treatment will relieve hyper-phosphorylation of neurogranin.

• Biomolecules & Therapeutics
• /
• v.18 no.1
• /
• pp.24-31
• /
• 2010

Taurine, 2-aminoethanesulfonic acid, is an abundant free amino acid present in brain cells and exerts many important biological functions such as anti-convulsant, modulation of neuronal excitability, regulation of learning and memory, anti-aggressiveness and anti-alcoholic effects. In the present study, we investigated to explore whether taurine has any protective actions against oxidative stress-induced damages in neuronal cells. ERK I/II regulates signaling pathways involved in nitric oxide (NO) and reactive oxygen species (ROS) production and plays a role in the regulation of cell growth, and apoptosis. We have found that taurine significantly inhibited AMPA induced cortical depolarization in the Grease Gap assays using rat cortical slices. Taurine also inhibited AMPA-induced neuronal cell damage in MTT assays in the differentiated SH-SY5Y cells. When the neuronal cells were treated with $H_2O_2$, levels of NO were increased; however, taurine pretreatment decreased the NO production induced by $H_2O_2$ to approximately normal levels. Interestingly, taurine treatment stimulated ERK I/II activity in the presence of AMPA or $H_2O_2$, suggesting the potential role of ERK I/II in the neuroprotection of taurine. Taken together, taurine has significant neuroprotective actions against AMPA or $H_2O_2$ induced damages in neuronal cells, possibly via activation of ERK I/II.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.2845-2850
• /
• 2013

Background: Breast cancer is one of the most frequent diseases in women today. Little information exists on modifiable lifestyle factors including effects of ginger supplements (as an anti-oxidant and anti-inflammatory herbal) and water-based exercise on biomarkers related to oxidative stress such as malondialdehyde (MDA), nitric oxide (NO) and glutathione peroxidase (GPx) and adiponectin in obese women with breast cancer. The aim of this study was to determine the single and concomitant effect of 6-wks water-based exercise and oral ginger supplement on the aforesaid markers in obese women with breast cancer. Materials and Methods: Forty women diagnosed with breast cancer ($48{\pm}5.4$ years, $76{\pm}9$ kg, fat mass $41.8{\pm}4%$), volunteered to participate in the study. Subjects were randomly assigned into four groups; placebo, water-based exercise, ginger supplement and water-based exercise+ginger supplement groups. Subjects in the ginger supplement group and the water-based exercise+ginger supplement group orally received 4 capsules (each capsule contained 750 mg), 7 days a week for 6 weeks. The water-based exercise program featured progressive increase in intensity and time, ranging from 50% to 75% of heart rate reserve, in a pool with 15 meters width, 4 times a week for 6 weeks. Fasting blood samples were collected at pre-test and post-test time points. Results: The ginger supplementation and or the water-base exercise resulted in an increase of adiponectin, NO and GPx and reduction MDA, as compared to pre-test values. However, the combined intervention (water-base exercise and ginger supplement) group showed significantly a far better effect on the biomarkers related to oxidative stress and adiponectin levels, as compared to the waterbase exercise or ginger supplement alone groups and the age-matched placebo group. Conclusions: Our results revealed that water-base exercise is a non-drug therapeutic strategy to reduce systemic stress in obese women suffering from breast cancer. Further, ginger supplementation alone or in combination with training, also play an important role in the pathogenesis of oxidative stress in obese women diagnosed with breast cancer.

• Asian-Australasian Journal of Animal Sciences
• /
• v.24 no.6
• /
• pp.818-824
• /
• 2011

Eight LW${\times}$D crossbred, castrated weanling piglets were used to examine the effect of hyperglycemia by streptozotocin (STZ)-injection on oxidative and anti-oxidative status in circulating fluid. Every two of the eight piglets were intravenously administrated STZ at a dose of 0 (control), 100, 125 or 150 mg/kg BW, respectively, and on 15th day after the STZ-injection, some markers of the oxidative stress in circulating fluid were measured to evaluate oxidative and anti-oxidative status in the piglets. First, piglets with hyperglycemia were selected from the STZ-injected piglets as measured by the levels of fasting plasma glucose (FPG) during 2 weeks after the STZ-injection. Additionally, data obtained from the intravenous glucose tolerance test (IVGTT) on 14th day were analyzed. Secondly, the data obtained in this experiment were divided into the control group and the hyperglycemic (STZ) group, and compared. The FPG level or area under curve (AUC) for plasma glucose during the IVGTT in the STZ-induced diabetic piglets was slightly significantly (FPG, p = 0.070; AUC, p = 0.072) higher compared with the control. On the other hand, the plasma level of lipid peroxidation in the STZ-induced diabetic piglets was significantly (p<0.05) higher compared with the control. These results raise the possibility that STZ-induced diabetic piglets produced in this study can be used as a diabetic animal model to research the pathogenic mechanisms or therapy of complications in diabetic mellitus.

• Journal of Nutrition and Health
• /
• v.46 no.2
• /
• pp.126-136
• /
• 2013

This study was conducted in order to investigate the association between hypertension and oxidative stress-related parameters and to evaluate these parameters in subclinical hypertensive patients and normotensive subjects living in Korea. We attempted to determine whether oxidative stress-related parameters would differ between two groups of 227 newly-diagnosed, untreated (systolic blood pressure (BP) ${\geq}$ 130 mmHg and diastolic BP ${\geq}$ 85 mmHg) and 130 normotensive subjects (systolic BP < 120 mmHg and diastolic BP < 80 mmHg). General characteristics of the subjects were collected using a simple questionnaire. From subjects' blood, degree of DNA damage in lymphocytes, the activities of erythrocyte superoxide dismutase, catalase, and glutathione peroxidase, level of plasma total radical-trapping antioxidant potential (TRAP), glutathione, and anti-oxidative vitamins, as well as plasma lipid profiles and conjugated diene (CD) were analyzed. Evaluation of the associations of oxidative stress-related parameters with blood pressure of the subjects was performed using Pearson partial correlation and multivariate logistic regression analysis after adjusting for confounding factors. Several oxidative stress-related parameters were higher in subclinical hypertensive patients than in normotensive subjects. Plasma levels of ${\alpha}$-tocopherol, ${\beta}$-carotene, TRAP, and activity of GSH-px were significantly lower in subclinical hypertensive patients than in normotensive subjects. Increased levels of DNA damage, lipid peroxidation, triglyceride, total cholesterol, and LDL-cholesterol were observed in subclinical hypertensive patients. These results confirm an association between blood pressure and oxidative stress-related parameters and suggest that the pathogenic role of oxidative stress in hypertension might be significant.