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ABSTRACT: Capsaicin and resveratrol as natural products have a variety of beneficial effects. However, capsaicin is also a neurotoxic agent, rendering its effect on the nervous system confusing. The aim of this study was to investigate whether capsaicin and/or resveratrol have a protective effect against glutamate (Glu)-induced neurotoxicity. After exposure to glutamate for 15min, cerebral cortical neurons of ICR mouse fetuses on embryonic days 15-16 were post-treated with capsaicin and/or resveratrol for 24h. Glu induced a significant reduction in cell viability, but the cell viability increased significantly with capsaicin or resveratrol treatment and further was highest in the neurons co-treated with both phytochemicals. Glu-induced reactive oxygen species generation and apoptotic neuronal death also significantly decreased by a combined treatment with both phytochemicals. Due to Glu insults, the reduced mRNA levels of cytoplasmic glutathione peroxidase, copper/zinc and manganese superoxide dismutases, and Bcl-x(L) and the overexpressed mRNA levels of interleukin-1β and tumor necrosis factor-α were significantly restored by post-treatment of capsaicin and/or resveratrol. These findings indicate that capsaicin and resveratrol are neuroprotective against Glu-induced toxicity and that the combined treatment of both phytochemicals can enhance the neuroprotection, suggesting a useful therapeutic application in the treatment of neurodegenerative disorders.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 08/2012; 50(11):3877-85. · 2.99 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) is the most prevalent cause of dementia in the elderly people. The disease is pathologically characterized by extracellular deposition of beta-amyloid peptide (Aβ), cholinergic neurodegeneration and elevation of acetylcholine esterase (AChE) activity in the affected regions. In this study, we investigated the effects of obovatol on memory dysfunction, which was caused by scopolamine. Obovatol (0.2, 0.5 and 1 mg/kg for 7 day) attenuated scopolamine (1 mg/kg, i.p.)-induced amnesia in a dose-dependent manner, as revealed by the Morris water maze test and step-through passive avoidance test. Mechanism studies exhibited that obovatol dose-dependently alleviated scopolamine-induced increase in Aβ generation and β-secretase activity in the cortex and hippocampus. Obovatol also attenuated scopolamine-induced rise in AChE activity in the cortex and hippocampus. Obovatol might rescue scopolamine-mediated impaired learning and memory function by attenuating Aβ accumulation and stabilizing cholinergic neurotransmission, which suggests that the natural compound could be a useful agent for the prevention of the development or progression of AD neurodegeneration.
Archives of Pharmacal Research 07/2012; 35(7):1279-86. · 1.59 Impact Factor
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ABSTRACT: Nicotine, a major toxic component in tobacco smoke, leads to severe embryonic damage during organogenesis in embryos. We investigated whether resveratrol would positively influence nicotine-induced teratogenesis in mouse embryos (embryonic day 8.5) cultured for 48 h using a whole embryo culture system. Embryos exposed to nicotine (1mM) revealed significantly severe morphological anomalies, increased levels of caspase-3 mRNA and lipid peroxidation, and decreased levels of cytoplasmic superoxide dismutase (SOD), mitochondrial manganese SOD, cytosolic glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, hypoxia-inducible factor 1α, Bcl-x(L), and sirtuin1 (SIRT1) mRNAs and SOD activity compared to those in the normal control group. However, when resveratrol (1×10(-8) μM or 1×10(-7) μM) was added concurrently to the embryos exposed to nicotine, all the parameters in above improved conspicuously. These findings indicate that resveratrol has a noted protective effect against nicotine-induced teratogenesis in mouse embryos through its antioxidative and anti-apoptotic effects.
Reproductive Toxicology 06/2012; 34(3):340-6. · 3.23 Impact Factor
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Young-Jung Lee,
Dong-Young Choi,
Im Seop Choi,
Ki Ho Kim,
Young Hee Kim,
Hwan Mook Kim,
Kiho Lee,
Won Gil Cho,
Jea Kyung Jung,
Sang Bae Han,
Jin-Yi Han, Sang-Yoon Nam,
Young Won Yun,
Jae Hwang Jeong,
Ki-Wan Oh,
Jin Tae Hong
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ABSTRACT: Neuroinflammation is important in the pathogenesis and progression of Alzheimer disease (AD). Previously, we demonstrated that lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairments. In the present study, we investigated the possible preventive effects of 4-O-methylhonokiol, a constituent of Magnolia officinalis, on memory deficiency caused by LPS, along with the underlying mechanisms.
We investigated whether 4-O-methylhonokiol (0.5 and 1 mg/kg in 0.05% ethanol) prevents memory dysfunction and amyloidogenesis on AD model mice by intraperitoneal LPS (250 μg/kg daily 7 times) injection. In addition, LPS-treated cultured astrocytes and microglial BV-2 cells were investigated for anti-neuroinflammatory and anti-amyloidogenic effect of 4-O-methylhonkiol (0.5, 1 and 2 μM).
Oral administration of 4-O-methylhonokiol ameliorated LPS-induced memory impairment in a dose-dependent manner. In addition, 4-O-methylhonokiol prevented the LPS-induced expression of inflammatory proteins; inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes (expression of glial fibrillary acidic protein; GFAP) in the brain. In in vitro study, we also found that 4-O-methylhonokiol suppressed the expression of iNOS and COX-2 as well as the production of reactive oxygen species, nitric oxide, prostaglandin E2, tumor necrosis factor-α, and interleukin-1β in the LPS-stimulated cultured astrocytes. 4-O-methylhonokiol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus of the brain and cultured astrocytes. Consistent with the inhibitory effect on neuroinflammation, 4-O-methylhonokiol inhibited LPS-induced Aβ1-42 generation, β- and γ-secretase activities, and expression of amyloid precursor protein (APP), BACE1 and C99 as well as activation of astrocytes and neuronal cell death in the brain, in cultured astrocytes and in microglial BV-2 cells.
These results suggest that 4-O-methylhonokiol inhibits LPS-induced amyloidogenesis via anti-inflammatory mechanisms. Thus, 4-O-methylhonokiol can be a useful agent against neuroinflammation-associated development or the progression of AD.
Journal of Neuroinflammation 02/2012; 9:35. · 3.83 Impact Factor
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Young-Jung Lee,
Dong-Young Choi,
Yong Kyoung Lee,
Yoot Mo Lee,
Sang Bae Han,
Young Hee Kim,
Ki Ho Kim, Sang-Yoon Nam,
Beom Jun Lee,
Jong-Koo Kang,
Young Won Yun,
Ki-Wan Oh,
Jin Tae Hong
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ABSTRACT: Alzheimer's disease (AD), the most common form of dementia, is characterized by memory deficits and deposition of amyloid-β (Aβ) in the brain. It has been known that neuroinflammation and oxidative stress are critical factors in the development of AD. 4-O-methylhonokiol, an extract from Magnolia officinalis, is known to have anti-inflammatory and anti-oxidative effects. Thus, we investigated the properties of 4-O-methylhonokiol against progression and development of AD in Tg2576 mice. Tg2576 mice models show memory impairment and AD-like pathological features including Aβ deposition. Oral administration of 4-O-methylhonokiol through drinking water (1 mg/kg in 0.0002% Tween 80) for 12 weeks not only prevented memory impairment but also inhibited Aβ deposition. In addition, 4-O-methylhonokiol decreased β-secretase activity, oxidative lipid and protein damage levels, activation of astrocytes and microglia cells, and generation of IL-1β and TNF-α with increase of glutathione level in the brain. Our results showed that 4-O-methylhonokiol effectively prevented memory impairment by down-regulating β-secretase activity through inhibition of oxidative stress and neuroinflammatory responses in Tg2576 transgenic mice.
Journal of Alzheimer's disease: JAD 02/2012; 29(3):677-90. · 3.74 Impact Factor
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ABSTRACT: Excessive ethanol consumption during pregnancy causes fetal alcohol syndrome. We investigated the effect of [6]-gingerol on ethanol-induced embryotoxicity using a whole embryo culture system. The morphological changes of embryos and the gene expression patterns of the antioxidant enzymes cytosolic glutathione peroxidase (cGPx), cytoplasmic Cu/Zn superoxide dismutase (SOD1), and Mn-SOD (SOD2), and SOD activity were examined in the cultured mouse embryos exposed to ethanol (5 μL/3 mL) and/or [6]-gingerol (1×10(-8) or 1×10(-7) μg/mL) for 2 days. In ethanol-exposed embryos, the standard morphological score of embryos was significantly decreased compared with those of the control (vehicle) group. However, cotreatment of embryos with [6]-gingerol and ethanol significantly improved all of the developmental parameters except crownrump length and head length, compared with those of the ethanol alone group. The mRNA expression levels of cGPx and SOD2, not SOD1, were decreased consistently, SOD activity were significantly decreased compared with the control group. However, the decreases in mRNA levels of antioxidant enzymes and SOD activity were significantly restored to the control levels by [6]-gingerol supplement. These results indicate that [6]-gingerol has a protective effect against ethanol-induced teratogenicity during mouse embryogenesis.
Archives of Pharmacal Research 01/2012; 35(1):171-8. · 1.59 Impact Factor
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ABSTRACT: This study investigated the neuroprotective activity of red ginseng extract (RGE, Panax ginseng, C. A. Meyer) against kainic acid- (KA-) induced excitotoxicity in vitro and in vivo. In hippocampal cells, RGE inhibited KA-induced excitotoxicity in a dose-dependent manner as measured by the MTT assay. To study the possible mechanisms of the RGE-mediated neuroprotective effect against KA-induced cytotoxicity, we examined the levels of intracellular reactive oxygen species (ROS) and [Ca(2+)](i) in cultured hippocampal neurons and found that RGE treatment dose-dependently inhibited intracellular ROS and [Ca(2+)](i) elevation. Oral administration of RGE (30 and 200 mg/kg) in mice decreased the malondialdehyde (MDA) level induced by KA injection (30 mg/kg, i.p.). In addition, similar results were obtained after pretreatment with the radical scavengers Trolox and N, N'-dimethylthiourea (DMTU). Finally, after confirming the protective effect of RGE on hippocampal brain-derived neurotropic factor (BDNF) protein levels, we found that RGE is active compounds mixture in KA-induced hippocampal mossy-fiber function improvement. Furthermore, RGE eliminated 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and the IC(50) was approximately 10 mg/ml. The reductive activity of RGE, as measured by reaction with hydroxyl radical ((•)OH), was similar to trolox. The second-order rate constant of RGE for (•)OH was 3.5-4.5 × 10(9) M(-1)·S(-1). Therefore, these results indicate that RGE possesses radical reduction activity and alleviates KA-induced excitotoxicity by quenching ROS in hippocampal neurons.
Evidence-based Complementary and Alternative Medicine 01/2012; 2012:479016. · 4.77 Impact Factor
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ABSTRACT: Plasma glutathione peroxidase (pGPx) is an extracellular antioxidative selenoenzyme which has been detected in various adult tissues, but little is known about the expression and distribution of pGPx during embryogenesis. To investigate the expression patterns of pGPx during embryogenesis, we performed quantitative real-time PCR, in situ hybridization, Western blot, and immunohistochemistry analyses in whole embryos or each developing organ of mice on embryonic days (E)7.5-18.5. In whole embryos of E7.5-8.5, pGPx mRNA was more typically expressed in extra-embryonic tissues including ectoplacental cone, trophectoderm, and decidual cells than in embryos. However, after E9.5, pGPx mRNA and protein levels were increased in the embryos with differentiation and growth, but trended to gradually decrease in the extra-embryonic tissues until E18.5. In sectioned embryonic tissues on E13.5-18.5, pGPx mRNA and protein were mainly expressed in the developing nervous tissues, the sensory organs, and the epithelia of lung, skin, and intestine, the heart and artery, and the kidney. In particular, pGPx immunoreactivity was very strong in the developing liver. These results indicate that pGPx is spatio-temporally expressed in various embryonic organs as well as extra-embryonic tissues, suggesting that pGPx may function to protect the embryos against endogenous and exogenous reactive oxygen species during organogenesis.
Journal of molecular histology 09/2011; 42(6):545-56. · 1.75 Impact Factor
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ABSTRACT: Although it has been suggested that the transcription of phospholipid hydroperoxide glutathione peroxidase (PHGPx), an essential antioxidant selenoenzyme, may be affected by the estrogen state in mammals, the direct mechanism underlying the regulation of the PHGPx gene by estrogens in mammalian tissues remains to be clearly elucidated. In this study, we evaluated the expression of the PHGPx mRNA in cultured mouse fetuses (embryonic days 8.5-10.5) exposed to 17β-estradiol (E(2); 0.1, 1, 10, 100, and 1,000 ng/ml); estrogen receptor (ER) agonists [propyl pyrazole triol (PPT, an ERα-selective ligand, 1 μl/ml) and diarylpropionitrile (DPN, an ERβ-selective ligand, 1 μl/ml)]; and/or ER antagonist [ICI 182,780 (ICI, 1 μl/ml)] using a whole embryo culture system. E(2)-alone treatment significantly stimulated the expressions of both ERα and ERβ mRNAs in all the cultured fetuses (p < 0.05), although the ERβ mRNA levels were higher than ERα mRNA. PHGPx mRNA expression was significantly increased in all the fetuses treated with E(2) (1-1,000 ng/ml), PPT, and DPN (p < 0.05). Furthermore, pretreatment with ICI completely blocked the E(2)-induced PHGPx mRNA expression in the fetuses. In addition, the mRNA levels of cytosolic GPx, the other intracellular antioxidant selenoenzyme, did not differ significantly from the controls by an exposure to those agents. These results suggest that the PHGPx gene is regulated via an estrogen and ER signal pathway in the cultured mouse fetus.
In Vitro Cellular & Developmental Biology - Animal 06/2011; 47(8):535-40. · 1.31 Impact Factor
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ABSTRACT: Abstract This study investigated the anxiolytic-like effects of 4-O-methylhonokiol, a neolignan compound of Magnolia officinalis, by using the experimental paradigms of anxiety and compared the results with those of a known anxiolytic, diazepam. A single treatment with 4-O-methylhonokiol (0.1, 0.2, and 0.5 mg/kg, p.o.) or treatment for 7 days (0.5 mg/kg in drinking water) increased the percentage of time spent in the open arms and the number of open arms entries in the elevated plus-maze test. However, the 4-O-methylhonokiol-increased percentage of time spent in the open arm was abolished by treatment with flumazenil, a benzodiazepine receptor antagonist (10 mg/kg). 4-O-Methylhonokiol also increased the number of head dips in the hole-board test, but decreased locomotor activity. Molecular experiments revealed that the α1-subunit of γ-aminobutyric acid (GABA) type A receptors was overexpressed in the cortex of brains of mice after treatment with 4-O-methylhonokiol for 7 days. In addition, 4-O-methylhonokiol also increased chloride influx in cultured cortical cells. It is concluded that 4-O-methylhonokiol may have anxiolytic-like effects and that these effects may be mediated by GABAergic transmission with the increase of Cl(-) channel opening.
Journal of medicinal food 04/2011; 14(7-8):724-31. · 1.39 Impact Factor
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ABSTRACT: Myeloid differentiation 2 (MD-2) recognizes endotoxin lipopolysaccharide (LPS), which is required for Toll-like receptor 4 (TLR4) activity. MD-2 represents a more attractive therapeutic target than TLR4 for intervention in severe inflammatory disorders due to microbial infection. Here, we suggest MD-2 as a molecular target of nonlipid chalcone in the inhibition of LPS-induced cellular inflammation. A chalcone derivative, 2',4-dihydroxy-6'-isopentyloxychalcone (JSH) competitively displaced LPS from MD-2, and was fitted into the ligand-binding site on the crystal structure of MD-2 under the most energetically favorable simulation. JSH nullified TLR4 activation mechanism and sequentially inhibited nuclear factor-κB (NF-κB) activation that involves the phosphorylation and degradation of inhibitory κBs and the nuclear import and transcriptional activity of NF-κB in LPS-activated macrophages. Moreover, JSH suppressed NF-κB-target inflammatory genes such as inducible nitric oxide synthase, cyclooxygenase-2, interleukin-1β (IL-1β) and IL-6. Taken together, this study assigns the chalcone structure as an LPS antagonist binding to MD-2 with therapeutic potential against inflammatory conditions.
The Journal of Infectious Diseases 04/2011; 203(7):1012-20. · 6.41 Impact Factor
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ABSTRACT: Excess hypoxia during embryonic organogenesis leads to developmental abnormalities and postnatal deficits. To determine whether emodin and [6]-gingerol affects hypoxia-induced anomalies during embryonic organogenesis, we cultured embryonic day 8.5 mouse embryos under hypoxic conditions (5% O(2)) for 2 days with or without emodin (1 × 10(-8) μg/mL), [6]-gingerol (1 × 10(-9) μg/mL), and SOD mimetics MnTBAP (1 × 10(2) nM/mL) and then investigated the developmental changes and expression patterns of hypoxia-inducible factor 1α (HIF-1α), cytoplasmic superoxide dismutase (SOD1), and mitochondrial SOD (SOD2) in the embryos. Hypoxic conditions induced various developmental anomalies in the growth stages and remarkably low levels of HIF-1α, SOD1 and SOD2 mRNAs, and SOD activity in the embryos; however, these effects were significantly reversed by treatment with emodin, [6]-gingerol, and MnTBAP, respectively. Our findings indicate that antioxidants such as emodin, [6]-gingerol, and MnTBAP lessen hypoxia-induced embryotoxicities via upregulation of HIF-1α and intracellular SODs.
Reproductive Toxicology 03/2011; 31(4):513-8. · 3.23 Impact Factor
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ABSTRACT: Selenium (Se) is known to prevent several cancers while the relationship between high iron and the risk of colorectal cancer is controversial. To investigate the effects of Se in colon carcinogenesis, we subjected three different levels of Se and high-iron diet to a mouse model of colon cancer in which animals were treated with three azoxymethane (AOM) injections followed by dextran sodium sulfate (DSS) administration. There were five experimental groups including vehicle group [normal-Fe (NFe, 45 ppm)+medium-Se (MSe, 0.1 ppm)], positive control group (AOM/DSS+NFe+MSe), AOM/DSS+high-Fe (HFe, 450 ppm)+low-Se (LSe, 0.02 ppm), AOM/DSS+HFe+MSe, and AOM/DSS+HFe+high-Se (HSe, 0.5 ppm). The animals were fed on the three different Se diets for 24 weeks. The incidence of colon tumor in the high-Se diet group (AOM/DSS+HFe+HSe) showed 19.4% lower than positive control group, 5.9% lower than AOM/DSS+HFe+MSe diet group, and 11.1% lower than AOM/DSS+HFe+LSe group. The tumor multiplicity was significantly higher in the low-Se diet group (AOM/DSS+HFe+LSe) compare to all other AOM/DSS treated groups. In the high-Se diet group, the activity of hepatic GPx was comparable to that of positive control group, and significantly higher than those of low-Se or medium-Se diet groups. Expression level of hepatic GPx-1 showed similar results. Hepatic malondialdehyde (MDA) level (indicator of oxidative stress) in the low-Se diet group showed the highest compared to the other groups, and it was significantly higher than positive control group. In the high-Se diet group the level of MDA in the liver was significantly lower than all other AOM/DSS treated groups. High-Se diet group showed significantly lower proliferative index than low-Se and medium-Se groups. The apoptotic indices in low-Se group and medium-Se group were significantly lower than positive control group. However, apoptotic index of high-Se diet group was significantly higher than all other AOM/DSS treated groups. These findings suggest that dietary Se supplement may have protective effect against colon cancer by decreasing proliferation, increasing apoptosis of tumor cells, and reducing oxidative stress in mice with high iron diet.
Laboratory animal research. 03/2011; 27(1):9-18.
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ABSTRACT: Epilepsy is a neurodegenerative disease with periodic occurrences of spontaneous seizures as the main symptom. The aim of this study was to investigate the neuroprotective effects of capsaicin, the major ingredient of hot peppers, in a kainic acid (KA)-induced status epilepticus model. After intraperitoneal injections of KA (30mg/kg) in 8-week-old male ICR mice, the animals were treated subcutaneously with capsaicin (0.33mg/kg or 1mg/kg) and then examined for any anti-ictogenic, hypothermic, antioxidative, anti-inflammatory, and anti-apoptotic effects of the capsaicin treatment 3 days after KA treatment. KA injections significantly enhanced neurodegenerative conditions but co-injection with capsaicin reduced the detrimental effects of KA in a dose-dependent manner in mice. The co-administered group that received KA and 1mg/kg of capsaicin showed significantly decreased behavioral seizure activity and body temperature for 3h and also remarkably blocked intense and high-frequency seizure discharges in the parietal cortex for 3 days compared with those that received KA alone. Capsaicin treatment significantly diminished the levels of oxidant activity and malondialdehyde concentration and increased the antioxidant activity in the blood and brain of KA-treated mice. In addition, capsaicin significantly lowered the KA-induced increase in the concentration of the cytokines IL-1β and TNF-α in the brain. Furthermore, co-treatment of KA and capsaicin (1mg/kg) resulted in considerably decreased apoptotic cell death in the cornu ammonis sections of the hippocampus compared with that seen in the KA-alone group. These findings indicate that capsaicin is preventative for the epileptogenesis induced by KA in mice.
Neurochemistry International 02/2011; 58(6):634-40. · 2.86 Impact Factor
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ABSTRACT: This study attempted to clarify whether cocaine withdrawal altered sleep architecture and the role of adenosine receptors in this process. Cocaine (20 mg/kg) was administered subcutaneously once per day for 7 days to rat implanted with sleep/wake recording electrode. Polygraphic signs of undisturbed sleep/wake activities were recorded for 24 h before cocaine administration (basal recording as control); withdrawal-day 1 (after 1 day of repeated cocaine administration), withdrawal-day 8 (after 8 days of repeated cocaine administration), and withdrawal-day 14 (after 14 days of repeated cocaine administration), respectively. On cocaine withdrawal-day 1, wakefulness was significantly increased, total sleep was decreased, non-rapid eye movement sleep was markedly reduced, and rapid eye movement sleep was enhanced. Sleep/wake cycles were also increased on cocaine withdrawal day 1. However, non-rapid eye movement sleep was increased on withdrawal-day 8 and 14, whereas rapid eye movement sleep was decreased and no significant changes were observed in the total sleep and sleep/wake cycles during these periods. Adenosine A(2A) receptors expression was increased on withdrawal-day 8 and 14, whereas A(1) receptors levels were reduced after 14 days of withdrawal and the A(2B) receptors remained unchanged. Our findings suggest that alterations of sleep and sleep architecture during cocaine subacute and subchronic withdrawals after repeated cocaine administration may be partially involved in A(2A) receptors over-expression in the rat hypothalamus.
Archives of Pharmacal Research 02/2011; 34(2):281-7. · 1.59 Impact Factor
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ABSTRACT: The balance between reactive oxygen species production and antioxidant defense enzymes in embryos is necessary for normal embryogenesis. To determine the dynamic expression profile of manganese superoxide dismutase (MnSOD) in embryos, which is an essential antioxidant enzyme in embryonic organogenesis, the expression level and distribution of MnSOD mRNA and protein were investigated in mouse embryos, as well as extraembryonic tissues on embryonic days (EDs) 7.5-18.5. MnSOD mRNA levels were remarkably high in extraembryonic tissues rather than in embryos during these periods. MnSOD protein levels were also higher in extraembryonic tissues than in embryos until ED 16.5, but the opposite trend was found after ED 17.5. MnSOD mRNA was observed in the chorion, allantois, amnion, ectoderm, ectoplacental cone and neural fold at ED 7.5 and in the neural fold, gut, ectoplacental cone, outer extraembryonic membranes and primitive heart at ED 8.5. After removing the extraembryonic tissues, the prominent expression of MnSOD mRNA in embryos was seen in the sensory organs, central nervous system and limbs on EDs 9.5-12.5 and in the ganglia, spinal cord, sensory organ epithelia, lung, blood cells and vessels, intestinal and skin epithelia, hepatocytes and thymus on EDs 13.5-18.5. Strong MnSOD immunoreactivity was observed in the choroid plexus, ganglia, myocardium, blood vessels, heapatocytes, pancreatic acinus, osteogenic tissues, brown adipose tissue, thymus and skin. These findings suggest that MnSOD is mainly produced from extraembryonic tissues and then may be utilized to protect the embryos against endogenous or exogenous oxidative stress during embryogenesis.
The International journal of developmental biology 01/2011; 55(3):327-34. · 2.16 Impact Factor
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ABSTRACT: Although extracellular superoxide dismutase (EC-SOD), which scavenges the superoxide anion in extracellular spaces, has previously been implicated in the prenatal pulmonary response to oxidative stress in the developing lungs, little is currently known regarding the schematic expression pattern and the roles played by EC-SOD during embryogenesis. In an effort to characterize the pattern of EC-SOD expression during mouse organogenesis, quantitative RT-PCR, Western blotting, and in situ hybridization analyses were conducted in mouse embryos and extraembryonic tissues including placenta on embryonic days (Eds) 7.5-18.5. EC-SOD mRNA and protein were expressed in all the embryos and extraembryonic tissues examined. The mRNA level was higher in the embryos than the extraembryonic tissues on Eds 7.5-10.5, but after Ed 13.5, it evidenced an increasing pattern in the extraembryonic tissues. EC-SOD immunoreactivity also increased in the extraembryonic tissues after Ed 13.5. During organogenesis, EC-SOD mRNA was expressed principally in the ectoplacental cone, amnion, and neural ectoderm on Ed 7.5 and in the neural folds and primitive streak on Ed 8.5. On Eds 9.5-12.5, EC-SOD mRNA was expressed abundantly in the nervous tissues and forelimb and hindlimb buds. On Eds 13.5-18.5, EC-SOD mRNA was observed at high levels in the airway epithelium of lung, liver, the intestinal epithelium, skin, vibrissae, the metanephric corpuscle of kidney, the nasal cavity, and the labyrinth trophoblast, spongiotrophoblast, and blood cells in placenta. Our overall results indicate that EC-SOD is expressed spatiotemporally in developing embryos and surrounding extraembryonic tissues during mouse organogenesis, thus suggesting that EC-SOD may be relevant to organogenesis, playing the role of an antioxidant enzyme against endogenous and exogenous oxygen stresses.
Gene Expression Patterns 12/2010; 11(3-4):207-15. · 2.02 Impact Factor
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ABSTRACT: Resveratrol (trans-3,4',5-trihydroxystilbene) is one of nonflavonoid polyphenolic phytoalexins found in various plant species, a number of which are components of human diet including grapes and red wines. Resveratrol has exerted several beneficial effects with anti-inflammation, cardioprotection and cancer chemoprevention. However, its mechanisms of action are not completely understood. In this study, we investigated effects of resveratrol on inflammatory gene expression in interferon (IFN)-γ alone-stimulated macrophages and proposed a molecular basis underlying the action. Resveratrol inhibited IFN-γ-induced production of nitric oxide (NO), IFN-γ-inducible protein-10 (IP-10), or the monokine induced by IFN-γ (MIG) in RAW 264.7 macrophages and also that of NO in primary macrophages derived from bone marrows of C3H/HeJ (toll-like receptor-4(-/-)) mice. Moreover, resveratrol diminished IFN-γ-induced protein levels of inducible NO synthase (iNOS), attenuated mRNA levels of iNOS, IP-10 or MIG as well as inhibited IFN-γ-induced promoter activity of iNOS gene, indicating that the phytoalexin could down-regulate inflammatory genes at the transcription level. To understand a mechanism of the action, we tested resveratrol could affect the signal transducers and activation of transcription-1 (STAT-1), a pivotal transcription factor in IFN-γ-induced expression of inflammatory genes. Resveratrol inhibited IFN-γ-induced transcriptional activity of STAT-1 in macrophages and also IFN-γ-induced Tyr(701) or Ser(727) phosphorylation of STAT-1. We then focused on protein kinases upstream STAT-1 phosphorylation. Resveratrol inhibited IFN-γ-induced activation of Janus kinase-2 (JAK-2) and also the extracellular signal-regulated kinase, in which JAK-2 was more sensitive. Taken together, this study proposes a new mechanism of resveratrol, blocking JAK/STAT-1 pathway that controls inflammatory responses in IFN-γ-activated macrophages.
The Journal of nutritional biochemistry 12/2010; 22(10):902-9. · 4.29 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) is the most common form of dementia. It is characterized by extracellular deposition of a specific protein, beta-amyloid peptide fibrils, and is accompanied by extensive loss of neurons in the brains of affected individuals. Although the pathophysiologic mechanism is not fully established, inflammation appears to be involved. Neuroinflammation has been known to play a critical role in the pathogenesis of chronic neurodegenerative disease in general, and in AD in particular. Numerous studies show the presence of a number of markers of inflammation in the AD brain: elevated inflammatory cytokines and chemokines, and accumulation of activated microglia in the damaged regions. Epidemiological studies have shown that long-term use of non-steroidal anti-inflammatory drugs suppresses the progression of AD and delays its onset, suggesting that there is a close correlation between neuroinflammation and AD pathogenesis. The aim of this review is (1) to assess the association between neuroinflammation and AD through discussion of a variety of experimental and clinical studies on AD and (2) to review treatment strategies designed to treat or prevent AD.
Archives of Pharmacal Research 10/2010; 33(10):1539-56. · 1.59 Impact Factor
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Sunhee Shin,
Ja Young Jang,
Dongsun Park,
Jung-Min Yon,
In-Jeoung Baek,
Bang Yeon Hwang, Sang-Yoon Nam,
Young Won Yun,
Ki-Yon Kim,
Seong Soo Joo,
Yun-Bae Kim
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ABSTRACT: Ginseng has been used for a long time and is well tolerated in humans. However, recent studies have shown that ginsenosides Rb1, Rg1, and Re exert embryotoxicity in in vitro culture systems. We investigated the effects of Korean red ginseng extract (KRGE) on embryonic implantation and fetal development in mice.
Mice were orally administered KRGE (20, 200, or 2,000 mg/kg/day) from 2 weeks before mating to gestational day (GD) 18, and implantation rate, fetal mortality, body weights, as well as external, visceral, and skeletal abnormalities were determined by Caesarean section on GD18. Ginsenosides in KRGE and in the blood of dams were identified and quantified by HPLC analysis.
KRGE did not affect embryonic implantation and mortality as well as fetal body weights up to 2,000 mg/kg/day (approximately 200 times clinical doses), the upper-limit dose recommended by the Korea Food and Drug Administration (KFDA). Although the prevalence of supernumerary ribs increased at the medium dose (200 mg/kg/day), no dose-dependent increases in external, visceral, and skeletal abnormalities were observed. Major ginsenosides such as Rb1, Rg1, and Re were not detected in the blood of dams based on their chromatographic profiles.
Considerable developmental toxicities of KRGE, even at the upper-limit dose, were not observed in mice. These results might be due to the negligible blood concentrations of ginsenosides in their original forms following oral administration, suggesting that in vitro experiments to assess the effects of ginsenosides on embryotoxicity may not reliably explain the risks of ginsenosides to in vivo embryo-fetal development.
Birth Defects Research Part B Developmental and Reproductive Toxicology 02/2010; 89(1):78-85. · 1.93 Impact Factor
