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ABSTRACT: AIMS: The present study examined the effect of the heme oxygenase (HO)-1 inducer hemin on skeletal muscle atrophy induced by single limb immobilization in mice. MAIN METHODS: Immobilization was conducted in the left hindlimb of C57BL/6 mice for 1week and the right hindlimb was used as a control. Hemin (30mg/kg) was administered intraperitoneally once a day during the immobilization period. Gastrocnemius muscles were used for analysis. Muscle weight was measured to quantify degree of atrophy, and exhaustion treadmill test was performed to assess muscle function. KEY FINDINGS: Immobilization increased HO-1 protein levels in skeletal muscle, which was further increased by hemin treatment. Immobilization induced weight loss and a functional reduction in skeletal muscle, which were attenuated by hemin treatment. Gene expression and protein levels of MuRF1 and atrogin-1 were increased by immobilization and hemin treatment attenuated the increment. The phosphorylation of mTOR and p70S6k was decreased by immobilization in skeletal muscle and hemin had no effect on mTOR and p70S6k phosphorylation. Gene expression of the antioxidants superoxide dismutase and glutathione peroxidase 1 in skeletal muscle was reduced by immobilization and hemin treatment recovered the reduction. Immobilization increased levels of carbonylated protein and nitrotyrosine in skeletal muscle, which was reversed by hemin treatment. Gene expression of inflammatory cytokines was increased by immobilization and was normalized as a result of hemin treatment. SIGNIFICANCE: These results suggest that hemin attenuates immobilization-induced skeletal muscle atrophy through the suppression of protein degradation via its anti-oxidant and anti-inflammatory properties.
Life sciences 02/2013; · 2.56 Impact Factor
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ABSTRACT: The present study examined whether insulin-like growth factor binding protein 5 (IGFBP5) is involved in the high glucose-induced deteriorating effects in cardiac cells. Cardiac fibroblasts and cardiomyocytes were isolated from the hearts of 1-3-day-old Sprague-Dawley rats. Treatment of fibroblasts with 25 mM glucose increased the number of cells and the mRNA levels of collagen III, matrix metalloproteinase (MMP) 2, and MMP9. High glucose increased extracellular signal-regulated kinase (ERK) 1/2 activity, and the ERK1/2 inhibitor PD98059 suppressed the high glucose-mediated fibroblast proliferation and increased collagen III mRNA levels. Whereas high glucose increased both mRNA and protein levels of IGFBP5 in fibroblasts, high glucose did not affect IGFBP5 protein levels in cardiomyocytes. High glucose-induced increase in IGFBP5 protein levels was inhibited by PD98059 in fibroblasts. While recombinant IGFBP5 increased ERK phosphorylation, cell proliferation, and the mRNA levels of collagen III, MMP2 and MMP9 in fibroblasts, IGFBP5 increased c-Jun N-terminal kinase phosphorylation and induced apoptosis in cardiomyocytes. The knockdown of IGFBP5 inhibited high glucose-induced cell proliferation and collagen III mRNA levels in fibroblasts. Although high glucose increased IGF1 levels, IGF1 did not increase IGFBP5 protein levels in fibroblasts. The hearts of Otsuka Long-Evans Tokushima Fatty rats and the cardiac fibroblasts of streptozotocin-induced diabetic rats showed increased IGFBP5 expression. These results suggest IGFBP5 mediates high glucose-induced profibrotic effects in cardiac fibroblasts.
Journal of Molecular Endocrinology 02/2013; · 3.48 Impact Factor
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ABSTRACT: Abstract Leptin resistance is a common feature of obesity and is accompanied by hyperleptinemia. Although leptin sensitizers improve leptin resistance, they also decrease plasma leptin levels that attenuate the leptin-associated antiobesity effect. We hypothesized that the combinational treatment of leptin sensitizer and endogenous leptin expression stimulant would synergistically induce an antiobesity effect in high-fat-fed obese animals. Betulinic acid (BA) isolated from Saussurea lappa suppressed the hypothalamic protein tyrosine phosphatase 1B in mice and enhanced the antiobesity effect of leptin in obese rats. Ethanol extract of Orthosiphon stamineus (OS) induced leptin expressions in both 3T3-L1 adipocytes and mice in a dose-dependent manner. To evaluate our hypothesis, we treated obese mice induced by 6 weeks of high-fat-diet feeding with BA and OS for 2 weeks. Although BA or OS alone did not decrease body weight in obese mice, the combinational treatment of BA and OS decreased body weight significantly compared to either BA- or OS-treated obese mice. These results suggest that combinational treatment of BA and OS would be effective for the treatment of obesity.
Journal of medicinal food 12/2012; · 1.39 Impact Factor
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ABSTRACT: Metformin, an oral biguanide insulin-sensitizing agent, is well known to decrease appetite. Although there is evidence that metformin could affect the brain directly, the exact mechanism is not yet known.
To evaluate whether metformin induces anorexia via the hypothalamus, various concentrations of metformin were injected into the lateral ventricle of rats through a chronically implanted catheter and food intake was measured for 24 hours. The hypothalamic neuropeptides associated with regulation of food intake were also analyzed following 1 hour of intracerebroventricular (ICV) injections of metformin.
An ICV injection of metformin decreased food intake in a dose-dependent manner in unrestrained conscious rats. Hypothalamic phosphorylated AMP-activated protein kinase (pAMPK) increased by 3 µg with metformin treatment, but there was no further increase in pAMPK with increases in metformin dosage. The hypothalamic phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased by 3 µg with metformin treatment, but, there was no further increase in pSTAT3 level following increases of metformin dosage. Hypothalamic proopiomelanocortin was elevated with metformin treatment, while neuropeptide Y was not significantly changed.
Our results suggest that metformin induces anorexia via direct action in the hypothalamus and the increase in pSTAT3, at least in part, is involved in the process. However, hypothalamic pAMPK appears not to contribute to metformin-induced appetite reduction in normal rats. Further studies exploring new pathways connecting metformin and feeding regulation are needed.
Diabetes & metabolism journal 08/2012; 36(4):293-9.
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ABSTRACT: BACKGROUND AND OBJECTIVES: This study was conducted to measure the level of health-related quality of life (HRQOL) and to reveal the association of self-efficacy and treatment satisfaction with it in Korean dialysis patients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The study subjects were 237 patients receiving either hemodialysis (HD) or peritoneal dialysis (PD) from two university hospitals, from February to June in 2010. We investigated HRQOL using the Korean version of Kidney Disease Quality of Life Short Form 36 (KDQOL-36), and self-efficacy and treatment satisfaction by self-administrative questionnaire and their dialysis-related variables by reviewing clinical records. The associations of self-efficacy and treatment satisfaction with HRQOL were assessed using multiple linear regression analysis. RESULTS: The mean HRQOL results were as follows: Physical component score (PCS) was 39.1 ± 8.5, Mental component score (MCS) 44.6 ± 6.8, symptom/problem list was 67.6 ± 17.1, effects of disease score was 58.5 ± 19.6, and burden of disease score was 41.1 ± 28.4. Between PD and HD patients, we could find significant difference only in the symptom/problem list. After removing confounder's effects by multivariate analysis, respectively, treatment goal self-efficacy and treatment management self-efficacy were significantly related with all 5 domains, except PCS. Treatment satisfaction was significantly related with PCS, MCS, and effects of kidney disease. CONCLUSIONS: Patients' self-efficacy and treatment satisfaction could influence their HRQOL. Regular and systematic monitoring using KDQOL-36 and interventions to increase self-efficacy and treatment satisfaction should be considered in dialysis care in Korea.
Quality of Life Research 05/2012; · 2.30 Impact Factor
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Canadian Journal of Anaesthesia 04/2012; 52:A164-A164. · 2.35 Impact Factor
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ABSTRACT: To develop a health-aid preparation of Chinese yam (Dioscorea batatas Decne), lactic acid fermentation was attempted using a mixed starter comprising ofLactobacillus acidophilus, Streptococcus thermophilus, andBifidobacterium bifidus. The anaerobic fermentation of a 5% Chinese yam flour suspension gave a uniform suspension of pH 4.35, containing 7.76×106 CFU/mL lactic acid bacteria (LAB), and which was found to be acceptable to the panel from a sensory assessment. During the
administration of the lactic acid fermented (LAF) Chinese yam to Sprague Dawley rats for 6 weeks, a smaller body weight gain,
but greater excretion of feces were observed, implying the creation of a healthy gastrointestine on the administration of
LAF Chinese yam, which was also confirmed by the gastrointestinal motility of the feed in rats fed on LAF Chinese yam. The
constipation induced by loperamide was further suppressed in a rat group fed on a LAF Chinese yam diet, which was qualified
from healthy gastrointestinal flora established by LAB. A serochemical analysis revealed a slight improvement in the blood
glucose, neutral lipid and total cholesterol concentrations on administration of LAF Chinese yam, suggesting LAF Chinese yam
could be served as a healthy-aid preparation, even for hyperglycemia or hyperlipidemia patients.
Biotechnology and Bioprocess Engineering 04/2012; 11(3):240-244. · 1.28 Impact Factor
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ABSTRACT: The present study examined the effects of inducible nitric oxide synthase (iNOS) deficiency on skeletal muscle atrophy in single leg-immobilized iNOS knockout (KO) and wild-type (WT) mice. The left leg was immobilized for 1 wk, and the right leg was used as the control. Muscle weight and contraction-stimulated glucose uptake were reduced by immobilization in WT mice, which was accompanied with increased iNOS expression in skeletal muscle. Deficiency of iNOS attenuated muscle weight loss and the reduction in contraction-stimulated glucose uptake by immobilization. Phosphorylation of Akt, mTOR, and p70S6K was reduced to a similar extent by immobilization in both WT and iNOS KO mice. Immobilization decreased FoxO1 phosphorylation and increased mRNA and protein levels of MuRF1 and atrogin-1 in WT mice, which were attenuated in iNOS KO mice. Aconitase and superoxide dismutase activities were reduced by immobilization in WT mice, and deficiency of iNOS normalized these enzyme activities. Increased nitrotyrosine and carbonylated protein levels by immobilization in WT mice were reversed in iNOS KO mice. Phosphorylation of ERK and p38 was increased by immobilization in WT mice, which was reduced in iNOS KO mice. Immobilization-induced muscle atrophy was also attenuated by an iNOS-specific inhibitor N(6)-(1-iminoethyl)-l-lysine, and this finding was accompanied by increased FoxO1 phosphorylation and reduced MuRF1 and atrogin-1 levels. These results suggest that deficiency of iNOS attenuates immobilization-induced skeletal muscle atrophy through reduced oxidative stress, and iNOS-induced oxidative stress may be required for immobilization-induced skeletal muscle atrophy.
Journal of Applied Physiology 04/2012; 113(1):114-23. · 3.75 Impact Factor
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ABSTRACT: The purpose of the present study was to determine whether exposure of pancreatic islets to glucotoxic conditions changes fatty acid translocase cluster determinant 36 (CD36) and examine the role of CD36 on the induction of glucotoxicity. We measured the changes of CD36 and insulin secretion in high glucose (30 mM) exposed INS-1 cells and CD36 suppressed INS-1 cells by transfection of CD36 siRNA. The intracellular peroxide level of INS-1 cells increased in the high glucose media compared to normal glucose (5.6mM) media. The mRNA levels of insulin and PDX-1, as well as glucose stimulated insulin secretion (GSIS) were decreased in INS-1 cells exposed to high glucose media compared to normal glucose media, while CD36 and palmitate uptake were significantly elevated with exposure to high glucose media for 12h. The inhibition of CD36 reversed the decreased GSIS and intracellular peroxide level in INS-1 cells. These results suggest that high glucose may exacerbate glucotoxicity via increasing fatty acid influx by elevation of CD36 expression, and that CD36 may be a possible target molecule for preventing glucotoxicity in pancreatic beta-cells.
Biochemical and Biophysical Research Communications 03/2012; 420(2):462-6. · 2.48 Impact Factor
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ABSTRACT: This study was conducted to observe recent changes in adolescents' dietary behavior and indirectly evaluate the effects of the government's nutritional policies in Korea.
We analyzed the secular trends in seven dietary behaviors using the Korea Youth Risk Behavior Web-based Survey data from 2005 to 2009. Through literature review, we included the policies implemented for the improvement of adolescents'dietary behaviors during the same periods.
The significant linear trends were observed in all dietary behaviors (p<0.05). Overall, all behaviors except the fruit intake rate were desirably changed during five years but undesirable changes were observed between 2008 and 2009 in all behaviors. Within those periods, several policies were implemented including 'Ban on carbonated-beverages in school', 'Green Food Zone', etc. Despite confirmed evidence of their effects, the policies on individual behavior such as nutrition education didn't influence the prevalence of dietary behaviors because they were conducted to too limited persons. Policies on the school environmental improvement, such as ban on carbonated beverage in school, were more effective because they decreased the exposure of undesirable food environment. However, for effect of Green Food Zone improving community environment we couldn't come to a conclusion because of too short period after full implementation.
Among government nutrition policies conducted from 2005 to 2009, those on environmental improvement, especially in school, were more effective than those on individual behavior. Therefore, the development and implement of policies on school environmental improvement are needed in Korea.
Journal of preventive medicine and public health = Yebang Ŭihakhoe chi. 01/2012; 45(1):47-59.
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Sun-Hee Park,
Jun-Young Do,
Yeong Hoon Kim,
Ho Yung Lee,
Beom Seok Kim,
Sug-Kyun Shin,
Hyun Chul Kim,
Yoon-Kyung Chang,
Jong-Oh Yang,
Hyun-Chul Chung,
Chan-Duck Kim,
Won Kee Lee, Jong-Yeon Kim,
Yong-Lim Kim
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ABSTRACT: The local peritoneal effects of low-glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF) have been extensively described. However, the systemic effects of prolonged prescription of these solutions are unknown. This study aimed to evaluate the effects of neutral pH and low-GDP PDF on systemic inflammation and endothelial dysfunction markers in peritoneal dialysis (PD) patients.
This is a multicenter, open labeled, randomized controlled trial including one hundred fifty-two patients initiating continuous ambulatory peritoneal dialysis for end-stage renal disease from seven centers in Korea. Participants were randomly allocated to conventional PDF (Stay safe®; Fresenius Medical Care, Bad Homburg, Germany) or low-GDP PDF (Balance®; Fresenius Medical Care) and were followed for 1 year. Primary outcome variable was the inflammation and endothelial dysfunction index (IEDI), a composite score derived from serum levels of soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cellular adhesion molecule (sVCAM)-1 and high-sensitivity C-reactive protein (hs-CRP). sICAM-1, sVCAM-1, residual renal function (RRF), peritoneal membrane transport characteristics, ultrafiltration volume and nutritional parameters were measured as secondary outcome variables.
Of 152 patients randomized, 146 (low-GDP: conventional PDF, 79:67) patients entered the trial (46% male, 53% with diabetes mellitus). At 12-month follow-up, the low-GDP group had significantly lower levels of IEDI, sICAM-1 and sVCAM-1 compared to the conventional group; hs-CRP was not different between groups. Peritoneal transport characteristics, RRF, nutritional parameters, incidence of peritonitis and death-censored technique survival were not different between groups.
Neutral pH and low-GDP PDF likely produce fewer changes in markers of endothelial dysfunction compared to conventional PDF in incident PD patients.
Nephrology Dialysis Transplantation 08/2011; 27(3):1191-9. · 3.40 Impact Factor
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ABSTRACT: Understanding recent trends in cigarette smoking among adolescents is important in order to develop strategies to prevent cigarette smoking. The aim of this study was to compare recent trends in cigarette smoking for adolescents living in rural areas, small towns and metropolitan cities in Korea.
The raw data from the Korea Youth Risk Behavior Web-based Survey (KYRBWS) from 2005 to 2009 were used. Data were analyzed by using the method of complex survey data analysis considering complex sampling design. Logistic regression models were used to evaluate significant linear time trends in cigarette smoking. The indicators of cigarette use behaviors were 'current smoking rate', 'frequent smoking rate', 'heavy smoking rate' and 'smoking experience rate before 13 years of age'. All analyses were conducted according to gender.
Statistically significant increasing trends in current smoking rate and frequent smoking rate were observed and borderline significant increasing trends in heavy smoking rate were shown among rural boys. Among metropolitan city boys, statistically significant increasing trends were also seen for frequent smoking. Statistically significant decreasing trends in current smoking rate were observed among small town and metropolitan city girls. Smoking experience rate before 13 years of age for rural girls decreased significantly.
Cigarette smoking prevalence among adolescents in the rural areas has increased in the last five years especially among boys. Our findings suggest that anti-tobacco program for adolescents should be conducted primarily for those in rural areas.
Journal of preventive medicine and public health = Yebang Ŭihakhoe chi. 07/2011; 44(4):176-84.
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ABSTRACT: The hypothalamus, the center for body weight regulation, can sense changes in blood glucose level based on ATP-sensitive potassium (K(ATP)) channels in the hypothalamic neurons. We hypothesized that a lack of glucose sensing in the hypothalamus affects the regulations of appetite and body weight.
To evaluate this hypothesis, the responses to glucose loading and high fat feeding for eight weeks were compared in Kir6.2 knock-out (KO) mice and control C57BL/6 mice, because Kir6.2 is a key component of the K(ATP) channel.
The hypothalamic neuropeptide Y (NPY) analyzed one hour after glucose injection was suppressed in C57BL/6 mice, but not in Kir6.2 KO mice, suggesting a blunted hypothalamic response to glucose in Kir6.2 KO mice. The hypothalamic NPY expression at a fed state was elevated in Kir6.2 KO mice and was accompanied with hyperphagia. However, the retroperitoneal fat mass was markedly decreased in Kir6.2 KO mice compared to that in C57BL/6 mice. Moreover, the body weight and visceral fat following eight weeks of high fat feeding in Kir6.2 KO mice were not significantly different from those in control diet-fed Kir6.2 KO mice, while body weight and visceral fat mass were elevated due to high fat feeding in C57BL/6 mice.
These results suggested that Kir6.2 KO mice showed a blunted hypothalamic response to glucose loading and elevated hypothalamic NPY expression accompanied with hyperphagia, while visceral fat mass was decreased, suggesting resistance to diet-induced obesity. Further study is needed to explain this phenomenon.
Diabetes & metabolism journal 06/2011; 35(3):219-25.
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Young Na Park,
Youn Ju Lee,
Jeon Hyeun Choi,
Meihua Jin,
Ju Hae Yang,
Ying Li,
Jiean Lee,
Xian Li,
Keuk-Jun Kim,
Jong Keun Son,
Hyeun Wook Chang, Jong Yeon Kim,
Eunkyung Lee
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ABSTRACT: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for treating inflammatory diseases. The effects on OVA-induced asthmatic mice of an Inulae Flos extract (IFE) were evaluated in this study. The anti-asthmatic effects of IFE were determined by observing eosinophil recruitment, airway hyper-responsiveness (AHR), Th2 cytokine and IgE levels, and lung histopathology. The IFE treatment effectively reduced the percentage of eosinophils and Th2 cytokines in the bronchoalveolar lavage fluid (BALF) when compared to the levels in OVA-induced mice. IFE also suppressed AHR induced by aerosolized methacholine in OVA-induced mice. The results of the histopathological studies indicate that inflammatory cell infiltration and mucus hypersecretion were both inhibited by the IFE administration when compared to the effect on OVA-induced mice. The IFE treatment also suppressed the serum IgE levels and decreased Th2 cytokines in the supernatant of cultured splenocytes. These results suggest that IFE may have therapeutic potential against asthma.
Bioscience Biotechnology and Biochemistry 05/2011; 75(5):871-6. · 1.28 Impact Factor
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Jang-Hee Cho,
Jun-Young Do,
Sung-Ho Kim, Jong-Yeon Kim,
Jung-Ju Seo,
Ji-Young Choi,
Sun-Hee Park,
Chan-Duck Kim,
Sun-Young Jung,
Kyu-Hyang Cho,
Jong-Won Park,
Duk-Hyun Lee,
Kyung Eun Song,
Yong-Lim Kim
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 05/2011; 31(3):347-50.
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ABSTRACT: This study measured the impact of shifts in maternal age and parity on the increase in the low birth weight (LBW) rate in Korea.
We obtained raw data for all 6 397 945 live births registered at the Korea National Statistical Office between 1995 and 2005. We calculated the proportion of increment in the LBW rate due to changes in the distribution of maternal age and parity (AP-dis) and the proportion due to changes in the age- and parity-specific LBW rate (AP-spe).
The LBW rate increased from 3.02% in 1995 to 4.28% in 2005. The multiple birth rate increased from 1.32% to 2.19% during the same period. Of the 1.26% points increment in the LBW rate, 0.64% points occurred among singleton births and 0.62% points occurred among multiple births. Changes in the AP-dis accounted for 50% of the increase in the LBW rate among singleton births, but did not contribute to the increase in the LBW rate among multiple births. The remainder of the total increment in the LBW rate was explained by the increase in the AP-spe.
This study demonstrated that shifts in maternal age and parity among singleton births and increased multiple births were important contributors to the increment in the LBW rate. This study also revealed that the increase in the AP-spe was an equally important contributor as the shifts in maternal age and parity to the increment in the LBW rate among singleton births and was a major contributor among multiple births.
Journal of preventive medicine and public health = Yebang Ŭihakhoe chi. 05/2011; 44(3):111-7.
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ABSTRACT: We examined whether deletion of inducible nitric oxide synthase (iNOS) could prevent lipid infusion-induced insulin resistance in iNOS-knockout and wild-type mice with the in vivo euglycemic-hyperinsulinemic clamp technique. Plasma NO metabolites were increased in lipid-infused wild-type mice, while they were not increased in iNOS-knockout mice. Plasma tumor necrosis factor-α levels were increased in both wild-type and iNOS-knockout by lipid-infusion. Lipid infusion reduced glucose infusion rate (GIR) and whole body glucose uptake in wild-type mice, whereas iNOS-knockout mice displayed comparable GIR and whole body glucose uptake compared with the control. In the gastrocnemius, lipid infusion decreased glucose uptake and glycolysis that were accompanied with increased phosphorylation of c-Jun N-terminal kinase and reduced phosphorylation of phosphoinositide 3-kinases and serine/threonine kinase Akt. However, lipid infusion did not affect glucose uptake or phosphorylation of these proteins in iNOS-knockout mice. The mRNA levels of inflammatory cytokines were also increased in the gastrocnemis of wild-type and iNOS-knockout mice by lipid infusion. Nitrotyrosine level in the gastrocnemius was increased in lipid-infused wild-type mice but it was not increased in iNOS-knockout mice. These results suggest that lack of iNOS prevents lipid infusion-induced skeletal muscle insulin resistance without attenuating cytokine levels.
Journal of Pharmacological Sciences 01/2011; 117(2):77-86. · 2.08 Impact Factor
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ABSTRACT: The present study examined whether metformin treatment prevents isoporterenol-induced cardiac hypertrophy in mice. Chronic subcutaneous infusion of isoproterenol (15 mg/kg/24 h) for 1 week using an osmotic minipump induced cardiac hypertrophy measured by the heart-to-body weight ratio and left ventricular posterior wall thickness. Cardiac hypertrophy was accompanied with increased interleukin-6 (IL-6), transforming growth factor (TGF)-β, atrial natriuretic peptide (ANP), collagen I and III, and matrix metallopeptidase 2 (MMP-2). Coinfusion of metformin (150 mg/kg/24 h) with isoproterenol partially inhibited cardiac hypertrophy that was followed by reduced IL-6, TGF-β, ANP, collagen I and III, and MMP-2. Chronic subcutaneous infusion of metformin did not increase AMP-activated protein kinase (AMPK) activity in heart, although acute intraperitoneal injection of metformin (10 mg/kg) increased AMPK activity. Isoproterenol increased nitrotyrosine levels and mRNA expression of antioxidant enzyme glutathione peroxidase and metformin treatment normalized these changes. These results suggest that metformin inhibits cardiac hypertrophy through attenuating oxidative stress.
Korean Journal of Physiology and Pharmacology 12/2010; 14(6):377-84. · 0.96 Impact Factor
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Zhejiu Quan,
Youn Ju Lee,
Ju Hye Yang,
Yue Lu,
Ying Li,
Yeun-Kyung Lee,
Meihua Jin, Jong-Yeon Kim,
Joon Hyuk Choi,
Jong Keun Son,
Hyeun Wook Chang
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ABSTRACT: The aerial part of Saururus chinensis has been used in folk medicine to treat several inflammatory diseases in China and Korea. Previously, our group reported that anti-asthmatic activity of an ethanol extract of Saururus chinensis (ESC) might occur, in part, via the inhibition of prostaglandin D(2) (PGD(2)) and leukotriene C(4) (LTC(4)) production, and degranulation reaction in vitro, as well as through the down-regulation of interleukin (IL)-4 and eotaxin mRNA expression in an in vivo ovalbumin-sensitization animal model. However, the effects of Saururus chinensis on eicosanoid generation, as well as Th2 cytokines and eotaxin production in an in vivo asthma model, have not been fully investigated. Moreover, it has not been determined whether ESC can ameliorate airway inflammation in vivo. In the present study, we investigated the therapeutic activity of Saururus chinensis on ovalbumin (OVA)-sensitized airway inflammation and its major phytochemical compositions.
Asthma was induced in BALB/c mice by ovalbumin-sensitization and inhalation. ESC (10-100 mg/kg) or dexamethasone (5 mg/kg), a positive control, was administered 7 times orally every 12 h from one day before the first challenge to 1 h before the second challenge. The recruitment of inflammatory cells and hyperplasia of goblet cells were evaluated by H&E and PAS staining. Levels of Th2 cytokines, eotaxin, PGD(2) and LTC(4) were measured to evaluate the anti-inflammatory activity of ESC in OVA-sensitized mice. Contents of major components were analyzed by HPLC using a reversed-phase C18 column.
ESC (10 mg/kg) suppressed allergic airway inflammation by inhibition of the production of IL-4 (P<0.001), IL-5 (P<0.05), IL-13 (P<0.001), eotaxin (P<0.001), PGE(2) (P<0.001), LTC(4) (P<0.001) in lung extract and IgE level (P<0.001) in the serum. In addition, ESC (50 mg/kg) reduced the infiltration of inflammatory cells and hyperplasia of goblet cells in the lung tissues. The anti-inflammatory effect of ESC was comparable to that of the positive control drug, dexamethasone. Its major phytochemical composition includes manassantin A, B and sauchinone.
These results suggest that ESC decreased inflammation and mucus secretion in the OVA-induced bronchial asthma model, and its anti-asthmatic activity may occur in part via the inhibition of Th2 cytokines and eotaxin protein expression, as well as through prostaglandin E(2) (PGE(2)) and leukotriene C(4) (LTC(4)) generation. This effects may be attributed particularly to the presence of manassantin A, B and sauchinone major component evidenced by a HPLC analysis.
Journal of ethnopharmacology 10/2010; 132(1):143-9. · 2.32 Impact Factor
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ABSTRACT: The present study examined whether adiponectin can inhibit palmitate-induced apoptosis, and also the associated mechanisms and signal transduction pathways in human umbilical vein endothelial cells. Cells treated with 500 μM palmitate for 48 h increased reactive oxygen species (ROS) generation and induced apoptosis. Treatment with antioxidant N-acetyl-L-cysteine (1 mM) and globular adiponectin (5 μg/ml) inhibited palmitate-induced ROS generation and apoptosis. The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR; 1 mM), and cAMP activators forskolin (10 μM) and cholera toxin (200 ng/ml) also displayed the same effects. The inhibitory effects of adiponectin on ROS generation and apoptosis were reversed by the AMPK inhibitor compound C (40 μM), cAMP inhibitor SQ22536 (50 μM), and protein kinase A (PKA) inhibitor H-89 (10 μM). The inhibitory effect of forskolin on palmitate-induced apoptosis was reversed by compound C, whereas the inhibitory effect of AICAR was not reversed by SQ22536 and H-89. AICAR and forskolin could not inhibit palmitate-induced apoptosis in cells treated with dominant-negative AMPK. Forskolin increased phosphorylated AMPK at both Thr-172 and Ser-485/491. These results suggest that adiponectin inhibits palmitate-induced apoptosis by suppression of ROS generation via both the cAMP/PKA and AMPK pathways. Interaction between cAMP/PKA and AMPK pathways may be involved.
Journal of Endocrinology 10/2010; 207(1):35-44. · 3.55 Impact Factor