We attempted to examine anti-inflammatory and anti-oxidant effects of 4′-O-β-D-glucosyl-5-O-methylvisamminol (GOMV), the first epigenetic inhibitor of histone phosphorylation at Ser10. While GOMV did not affect the viability of murine macrophage RAW 264.7 cells, it significantly suppressed lipopolysaccharide (LPS)-induced generation of prostaglandin E₂ (PGE₂) and nitric oxide (NO) through transcriptional inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). GOMV also scavenged free radicals in vitro, increased NF-E2-related factor 2 (NRF2), and activated antioxidant response element (ARE), thereby resulting in the induction of phase II cytoprotective enzymes in human keratinocyte HaCaT cells. Finally, GOMV significantly protected HaCaT cells against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative intracellular damages. Together, our results illustrate that GOMV possesses anti-inflammatory and anti-oxidant activity.
Antioxidant Response Elements ; Antioxidants ; Cyclooxygenase 2 ; Epigenomics ; Free Radicals ; Histones ; Humans ; In Vitro Techniques ; Keratinocytes ; Macrophages ; NF-E2-Related Factor 2 ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phosphorylation ; RAW 264.7 Cells

BACKGROUND/OBJECTIVES: Vascular inflammation is an important feature in the atherosclerotic process. Recent studies report that leaves and branches of Carpinus turczaninowii (C. turczaninowii) have antioxidant capacity and exert anti-inflammatory effects. However, no study has reported the regulatory effect of C. turczaninowii extract on the arterial inflammatory response. This study therefore investigated modulation of the arterial inflammatory response after exposure to C. turczaninowii extract, using human aortic vascular smooth muscle cells (HAoSMCs). MATERIALS/METHODS: Scavenging activity of free radicals, total phenolic content (TPC), cell viability, mRNA expressions, and secreted levels of cytokines were measured in LPS-stimulated (10 ng/mL) HAoSMCs treated with the C. turczaninowii extract. RESULTS: C. turczaninowii extract contains high amounts of TPC (225.6 ± 21.0 mg of gallic acid equivalents/g of the extract), as well as exerts time-and dose-dependent increases in strongly scavenged free radicals (average 14.8 ± 1.97 µg/mL IC50 at 40 min). Cell viabilities after exposure to the extracts (1 and 10 µg/mL) were similar to the viability of non-treated cells. Cytokine mRNA expressions were significantly suppressed by the extracts (1 and 10 µg/mL) at 6 hours (h) after exposure. Interleukin-6 secretion was dose-dependently suppressed 2 h after incubation with the extract, at 1–10 µg/mL in non-stimulated cells, and at 5 and 10 µg/mL in LPS-stimulated cells. Similar patterns were also observed at 24 h after incubation with the extract (at 1–10 µg/mL in non-stimulated cells, and at 10 µg/mL in the LPS-stimulated cells). Soluble intracellular vascular adhesion molecules (sICAM-1) secreted from non-stimulated cells and LPS-stimulated cells were similarly suppressed in a dose-dependent manner after 24 h exposure to the extracts, but not after 2 h. In addition, sICAM-1 concentration after 24 h treatment was positively related to IL-6 levels after 2 h and 24 h exposure (r = 0.418, P = 0.003, and r = 0.524, P < 0.001, respectively). CONCLUSIONS: This study demonstrates that C. turczaninowii modulates the arterial inflammatory response, and indicates the potential to be applied as a therapeutic use for atherosclerosis.
Antioxidants ; Arteries ; Atherosclerosis ; Betulaceae ; Cell Survival ; Cytokines ; Free Radicals ; Gallic Acid ; Humans ; Inflammation ; Inhibitory Concentration 50 ; Interleukin-6 ; Muscle, Smooth, Vascular ; Phenol ; RNA, Messenger

BACKGROUND/OBJECTIVES: Excessive production of reactive oxygen species (ROS) such as hydroxyl (·OH), nitric oxide (NO), and hydrogen peroxide (H2O2) is reported to induce oxidative stress. ROS generated by oxidative stress can potentially damage glial cells in the nervous system. Cordyceps militaris (CM), a kind of natural herb widely found in East Asia. In this study, we investigated the free radical scavenging activity of the CM extract and its neuroprotective effects in H2O2-induced C6 glial cells. MATERIALS/METHODS: The ethanol extract of CM (100–1,000 µg/mL) was used to measure DPPH, ·OH, and NO radical scavenging activities. In addition, hydrogen peroxide (H2O2)-induced C6 glial cells were treated with CM at 0.5–2.5 µg/mL for measurement of cell viability, ROS production, and protein expression resulting from oxidative stress. RESULTS: The CM extract showed high scavenging activities against DPPH, ·OH, and NO radicals at concentration of 1,000 µg/mL. Treatment of CM with H2O2-induced oxidative stress in C6 glial cells significantly increased cell viability, and decreased ROS production. Cyclooxygenase-2 and inducible nitric oxide synthase protein expression was down-regulated in CM-treated groups. In addition, the protein expression level of phospho-p38 mitogen-activated protein kinase (p-p38 MAPK), phospho-c-Jun N-terminal kinase (p-JNK), and phospho-extracellular regulated protein kinases (p-ERK) in H2O2-induced C6 glial cells was down-regulated upon CM administration. CONCLUSION: CM exhibited radical scavenging activity and protective effect against H2O2 as indicated by the increased cell viability, decreased ROS production, down-regulation of inflammation-related proteins as well as p-p38, p-JNK, and p-ERK protein levels. Therefore, we suggest that CM could play the protective role from oxidative stress in glial cells.
Cell Survival ; Cordyceps ; Cyclooxygenase 2 ; Down-Regulation ; Ethanol ; Far East ; Free Radicals ; Hydrogen Peroxide ; Hydrogen ; In Vitro Techniques ; Nervous System ; Neuroglia ; Neuroprotective Agents ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Oxidative Stress ; Phosphotransferases ; Protein Kinases ; Reactive Oxygen Species

PURPOSE: This review article provides an overview of the trends of research papers on the health benefits of kimchi and kimchi lactic acid bacteria published from 1995 to 2017. METHODS: All publications from 1995 to 2017 regarding kimchi and kimchi lactic acid bacteria were collected, reviewed, and classified. This review article covers the publications of the health benefits of kimchi and kimchi lactic acid bacteria on experimental, clinical trials, and epidemiology studies. RESULTS: The number of publications on kimchi over the period were 590: 385 publications in Korean and 205 publications in English. The number of publications on the health benefits of kimchi and kimchi lactic acid bacteria were 95 in Korean and 54 in English. The number of publications on kimchi and kimchi lactic acid bacteria were 84 and 38, respectively, in the experimental models. Ten research papers on kimchi in clinical trials and 7 publications in epidemiology were found. Kimchi or kimchi lactic acid bacteria had protective effects against oxidative stress, mutagenicity, toxicity, cancer, dyslipidemia, hypertension, immunity, and inflammation in in vitro, cellular, and in vivo animal models. Moreover, kimchi had effects on the serum lipids, intestinal microbiota, iron status, obesity, and metabolic parameters in human clinical trials. In epidemiology, kimchi had effects on hypertension, asthma, atopic dermatitis, rhinitis, cholesterol levels, and free radicals. CONCLUSION: This review focused on the publications regarding the health benefits of kimchi and kimchi lactic acid bacteria, suggesting the future directions of studies about kimchi and kimchi lactic acid bacteria by producing a database for an evaluation of the health benefits of kimchi.
Asthma ; Bacteria ; Cholesterol ; Dermatitis, Atopic ; Dyslipidemias ; Epidemiology ; Free Radicals ; Gastrointestinal Microbiome ; Humans ; Hypertension ; In Vitro Techniques ; Inflammation ; Insurance Benefits ; Iron ; Lactic Acid ; Models, Animal ; Models, Theoretical ; Obesity ; Oxidative Stress ; Rhinitis

OBJECTIVE: Concerns about the safety of assisted reproductive technology (ART) have been raised, as some studies have shown elevated incidence rates of childhood cancer, asthma, allergies, and other diseases in ART-conceived babies. Findings regarding the health of ART-conceived babies are controversial. The present study was conducted to evaluate the prooxidant-antioxidant balance (PAB) in in vitro fertilization (IVF)-conceived mice in comparison to naturally conceived offspring. METHODS: Mice (6–8 weeks) were divided into two groups (IVF-conceived and naturally conceived) matched by sex, age, weight, and litter size. A 1-mL blood sample was taken and the sera were separated. The oxidant-antioxidant balance was evaluated using a fast and reliable PAB assay. The results were expressed as mean±standard deviation. RESULTS: The mean PAB values (HK units) in the IVF-conceived and naturally conceived groups were 59.70±22.30 and 54.70±18.22, respectively (p=0.82). CONCLUSION: Since free radicals contribute to several pathological conditions and antioxidants play an important protective role against oxidative stress, evaluating the oxidant-antioxidant balance is very important. Although the results of this study showed that the quality of the defense mechanism against free radicals was not significantly different between the IVF-conceived and naturally conceived mice, other parameters of metabolic dysfunction need to be measured.
Animals ; Antioxidants ; Asthma ; Fertilization in Vitro ; Free Radicals ; Hypersensitivity ; In Vitro Techniques* ; Incidence ; Litter Size ; Mice* ; Oxidative Stress ; Reproductive Techniques, Assisted

OBJECTIVE: Dapsone (diaminodiphenyl sulfone, DDS) is currently used to treat leprosy, malaria, dermatitis herpetiformis, and other diseases. It is also used to treat pneumocystis pneumonia and Toxoplasma gondii infection in HIV-positive patients. The most common adverse effect of DDS is methemoglobinemia from oxidative stress. Ascorbic acid is an antioxidant and reducing agent that scavenges the free radicals produced by oxidative stress. The present study aimed to investigate the effect of ascorbic acid in the treatment of DDS induced methemoglobinemia. METHODS: Male Sprague-Dawley rats were divided into three groups: an ascorbic acid group, a methylene blue (MB) group, and a control group. After DDS (40 mg/kg) treatment via oral gavage, ascorbic acid (15 mg/kg), MB (1 mg/kg), or normal saline were administered via tail vein injection. Depending on the duration of the DDS treatment, blood methemoglobin levels, as well as the nitric oxide levels and catalase activity, were measured at 60, 120, or 180 minutes after DDS administration. RESULTS: Methemoglobin concentrations in the ascorbic acid and MB groups were significantly lower compared to those in the control group across multiple time points. The plasma nitric oxide levels and catalase activity were not different among the groups or time points. CONCLUSION: Intravenous ascorbic acid administration is effective in treating DDS-induced methemoglobinemia in a murine model.
Animals ; Ascorbic Acid* ; Catalase ; Dapsone ; Dermatitis Herpetiformis ; Free Radicals ; Humans ; Leprosy ; Malaria ; Male ; Methemoglobin ; Methemoglobinemia* ; Methylene Blue ; Nitric Oxide ; Oxidative Stress ; Plasma ; Pneumonia, Pneumocystis ; Rats* ; Rats, Sprague-Dawley ; Tail ; Toxoplasmosis ; Veins

The circulatory system is closely related to the inter-relationship between the anatomy of the heart and blood vessels, and the fluid dynamic properties of blood. The physical properties of blood, which affect blood flow, are called hemorheologic factors. Hemorheologic factors, such as blood viscosity and erythrocyte aggregation, are influenced mainly by hematocrit. A higher hematocrit level results in an increase in blood viscosity, erythrocyte aggregation, which impedes the circulation itself, and tissue oxygenation. An excess of serum ferritin causes injury to vascular endothelial cells and erythrocytes via oxygen free radicals. In addition, an excess of blood can aggravatee the adverse effects of the hemorheologic parameters and induce atherogenesis, microcirculatory disturbances, and major cardiovascular events. A preventive and therapeutic approach with a phlebotomy or blood donation has been stimulated by the knowledge that blood loss, such as regular donations, is associated with significant decreases in key hemorheologic variables, including blood viscosity, erythrocyte aggregation, hematocrit, and fibrinogen. Major cardiovascular events have been improved in regular blood donors by improving blood flow and microcirculation by decreasing the level of oxidative stress, improving the hemorheologic parameters, and reducing the serum ferritin level. Confirmation of the positive preventive and therapeutic effects of blood donations on cardiovascular disease by a well-designed and well-controlled Cohort study may be good news to patients with cardiovascular disease or at risk of these diseases, as well as patients who require a transfusion.
Atherosclerosis ; Blood Donors* ; Blood Vessels ; Blood Viscosity ; Cardiovascular Diseases ; Cohort Studies ; Endothelial Cells ; Erythrocyte Aggregation ; Erythrocytes ; Ferritins ; Fibrinogen ; Free Radicals ; Heart ; Hematocrit ; Humans ; Hydrodynamics ; Microcirculation ; Oxidative Stress ; Oxygen ; Phlebotomy ; Therapeutic Uses

PURPOSE: The mechanism for the pathogenesis of adriamycin (ADR)-induced cardiomyopathy is not yet known. Different hypotheses include the production of free radicals, an interaction between ADR and nuclear components, and a disruption in cardiac-specific gene expression. Apoptosis has also been proposed as being involved in cardiac dysfunction. The purpose of this study was to determine if apoptosis might play a role in ADR-induced cardiomyopathy. METHODS: Male Sprague-Dawley rats were separated into 2 groups: the control group (C group) and the experimental group (ADR 5 mg/wk for 3 weeks through intraperitoneal injections; A group). Echocardiographic images were obtained at week 3. Changes in caspase-3, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), interleukin (IL)-6, tumor necrosis factor-α, brain natriuretic peptide (BNP), troponin I, collagen 1, and collagen 3 protein expression from the left ventricle tissues of C and A group rats were determined by Western blot. RESULTS: Ascites and heart failure as well as left ventricular hypertrophy were noted in the A group. Ejection fraction and shortening fraction were significantly lower in the A group by echocardiography. The expression of caspase-3, Bax, IL-6, BNP, collagen 1, and collagen 3 were significantly higher in the A group as compared with the C group. Protein expression of Bcl-2 decreased significantly in the A group compared with the C group. CONCLUSION: ADR induced an upregulation of caspase-3, Bax, IL-6, and collagen, as well as a depression in Bcl-2. Thus, apoptosis and fibrosis may play an important role in ADR-induced cardiomyopathy.
Animals ; Apoptosis* ; Ascites ; B-Lymphocytes ; Blotting, Western ; Cardiomyopathies* ; Caspase 3 ; Collagen ; Depression ; Doxorubicin ; Echocardiography ; Fibrosis ; Free Radicals ; Gene Expression ; Heart Failure ; Heart Ventricles ; Humans ; Hypertrophy, Left Ventricular ; Injections, Intraperitoneal ; Interleukin-6 ; Interleukins ; Male ; Models, Animal* ; Natriuretic Peptide, Brain ; Necrosis ; Rats* ; Rats, Sprague-Dawley ; Troponin I ; Up-Regulation ; Ventricular Remodeling

Preeclampsia (PE) is one of the major disorders in pregnancy leading to many adverse maternal outcomes. Although the etiology of PE is not fully understood, resent studies suggest that an imbalance between free radicals production and the antioxidant defense system might have key role. Our aim of the current study was to evaluate the association between dietary total antioxidant capacity (TAC), serum TAC and risk of PE in women with preeclampsia and normal pregnancy. This case-control study conducted on 55 women with preeclampsia and 93 with normal pregnancy. Dietary intakes were obtained by a semi-quantitative food frequency questionnaire (FFQ) with 168 itmes. Dietary TAC was assessed according to United States Department of Agriculture (USDA) Database for oxygen radical absorbance capacity (ORAC), Release 2. Serum TAC was measured by a double-antibody sandwich enzyme-linked immunesorbent assay (ELISA). After adjusting for energy, pre-pregnant body mass index (BMI) and history of PE, no relationship was found between intake of hydrophilic-ORAC (H-ORAC), lipophilic-ORAC (L-ORAC), total phenolics (TP), total-ORAC (T-ORAC), and PE risk. However, serum TAC had a significant positive relationship with the risk of PE after adjusting for energy (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.16–0.35), BMI and history of PE (OR, 0.04; 95% CI, 0.01–0.32). Findings of this study indicate that serum TAC is positively associated with the risk of PE but no association was found between intake of antioxidant indices and PE risk.
Body Mass Index ; Case-Control Studies ; Female ; Free Radicals ; Humans ; Oxygen ; Phenol ; Pre-Eclampsia* ; Pregnancy ; United States Department of Agriculture

BACKGROUND: Rice bran is the outer layer of the rice grain, and contains high amounts of bioactive phytochemicals. Here, we investigated and compared chemopreventive properties of purple and white rice bran extracts. METHODS: Rice bran was extracted with dichloromethane and methanol. Chemical constituents in the extracts were analyzed by colorimetric assay and high performance liquid chromatography. The mutagenicity and antimutagenicity of the extracts were determined via the Salmonella mutation assay. The anticarcinogenic enzyme induction and antioxidant activities of the extracts were examined using Hepa1c1c7 cells and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, respectively. RESULTS: The methanol extracts of rice bran contained high amounts of phenolic acids, flavonoids, anthocyanins, and phytic acid, whereas large amounts of γ-oryzanol and vitamin E were presented in the dichloromethane extract. None of the extracts were mutagenic to Salmonella typhimurium. All rice bran extracts had strong antimutagenic effects against aflatoxin B1- and 2-amino-3,4-dimethylimidazo [4,5-f]quinoline-induced mutagenesis. The inhibitory effect against 2-aminofluorene-induced mutagenesis was found in the dichloromethane extract, while only the methanol extract of purple rice bran exhibited antimutagenic effects against benzo(a)pyrene. None of the extracts induced quinone reductase activity in Hepa1c1c7 cells. Additionally, the greatest antioxidant capacity was found in the methanol extract of purple rice bran. CONCLUSIONS: The methanol extract of purple rice bran containing high amount of phenolic acids, flavonoids, anthocyanins, and phytic acid showed the most effective antioxidant and antimutagenic activities by inhibiting mutagenic metabolizing enzymes and/or scavenging free radicals. These results demonstrate the nutritional and medical value of Thai rice for cancer prevention.
Aflatoxins ; Anthocyanins ; Antimutagenic Agents ; Asian Continental Ancestry Group* ; Benzo(a)pyrene ; Chromatography, Liquid ; Enzyme Induction ; Flavonoids ; Free Radicals ; Humans ; Methanol ; Methylene Chloride ; Mutagenesis ; NAD(P)H Dehydrogenase (Quinone) ; Phenol ; Phytic Acid ; Phytochemicals ; Salmonella ; Salmonella typhimurium ; Vitamin E ; Vitamins