This study investigated the hypoglycemic, hypolipidemic, and antioxidant effects of dietary quercetin in an animal model of type 2 diabetes mellitus. Four-week-old C57BL/KsJ-db/db mice (n = 18) were offered an AIN-93G diet or a diet containing quercetin at 0.04% (low quercetin, LQE) or 0.08% of the diet (high quercetin, HQE) for 6 weeks after 1 week of adaptation. Plasma glucose, insulin, adiponectin, and lipid profiles, and lipid peroxidation of the liver were determined. Plasma glucose levels were significantly lower in the LQE group than in the control group, and those in the HQE group were even further reduced compared with the LQE group. The homeostasis model assessment for insulin resistance (HOMA-IR) showed lower values for LQE and HQE than for the control group without significant influence on insulin levels. High quercetin increased plasma adiponectin compared with the control group. Plasma triglycerides in the LQE and HQE groups were lower than those in the control group. Supplementation with high quercetin decreased plasma total cholesterol and increased HDL-cholesterol compared with the control group. Consumption of low and high quercetin reduced thiobarbituric acid reactive substances (TBARS) levels and elevated activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver. Thus, quercetin could be effective in improving hyperglycemia, dyslipidemia, and antioxidant status in type 2 diabetes.
These experiments were conducted to investigate the effects of glycyrrhizin(GL) and glycyrrhetinic acid(GA) on histamine synthesis, lymphocyte blastogenesis in C57BL/6J mice splenocytes, IL-1 production, $Ca^{2+}$ uptake by macrophage-like P388D$_{1}$ cells and plaque forming cell assay against SRBC. Histamine contents, lymphocyte blastogenesis, IL-1 activity, $Ca^{2+}$ uptake and plaque forming cell were determined by enzyme isotope method, [sup 3/H]-thymidine incorporation, C3H/HeJ mouse thymocytes proliferation, the addition of 5 $\mu$Ci/ml $^{45}$Ca$^{2+}$ to P388D$_{1}$, cell suspension and assay to sheep red blood cell, respectively. Cytotoxicity, which was expressed as 50% mortality, was occurred by the addition of GL(10$^{-3}$M) and GA(10$^{-4}$M). Histamine production in mouse spleen cell culture was significantly increased by the addition of 0.25 $\mu\textrm{g}$/ml of Con A, after 48 hour incubation. Con A dependent T-lymphocyte proliferation was also enhanced by the addition of 0.25 .mu.g/ml of Con A. The effects of GL on histamine contents and T-lymphocyte proliferation were significantly decreased at high dose (10$^{-5}$M), while IL-1 activity was remarkably suppressed by 10$^{-8}$~10$^{-4}$M of GL. $Ca^{2+}$ uptake was not changed, but antibody production was increased by GL(10 mg/kg). GA inhibited histamine contents at 10$^{-9}$~10$^{-7}$ and depressed Con A (0.25 $\mu\textrm{g}$/ml) dependent T-lymphocyte proliferation at 10$^{-7}$~10$^{-5}$M of GA, but increased suboptimal dose (Con A 0.1 $\mu\textrm{g}$/ml) at 10$^{-9}$~10$^{-7}$M of GA. IL-1 activity was suppressed by 10$^{-8}$~10$^{-4}$M of GA and $Ca^{2+}$ uptake was enhanced by 10$^{-9}$~10$^{-6}$ of GA, but antibody production was not changed by GA. From the above results, it is suggested that GL and GA have immuno-regulatory action. GL decreased cell-mediated immune response, and increased humoral immune response at high dose. On the other hand, low dose of GA enhanced cell-mediated immune response, while high doses of GA decreased humoral immune reaction.
Journal of Physiology & Pathology in Korean Medicine
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v.21
no.5
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pp.1163-1169
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2007
Effects of Sotosaja hwan on Blood Glucose, Hyperlipidemia, Polyol Pathway and Antioxidative Mechanism in ob/ob Mouse Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Sotosaja-hwan has been known to be effective for the antiaging and composed of four crude herbs. In male ob/ob mouse in severe obesity, hyperinsulinemia and hyperlipidemia, which are features of NIDDM, the hyperglycemic activites and mechanisms of Sotosaja-hwan were examined. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. The effects of Sotosaja-hwan extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of superoxide anion radical $({\cdot}O_2)$, MDA+HAE, GSH/GSSG ratio, and also the enzyme activities involved in polyol pathway. Sotosaja-hwan lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Sotosaja-hwan treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the generation of ${\cdot}O_2$ in the kidney. Finally, MDA+HAE levels was increased and GSH/GSSG ratio was decreased in the ob/ob mice, whereas those were improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan showed the antidiabetic and anti hyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging reactive oxygen species and reducing the MDA+HAE levels in the ob/ob mice.
BACKGROUND/OBJECTIVES: In this study, we investigated whether Gelidium amansii extract (GAE) ameliorates obesity in diet-induced obese (DIO) mice. MATERIALS/METHODS: The mice were maintained on a high-fat diet (HD) for 5 weeks to generate the DIO mouse model. And then mice fed HD plus 0.5% (GAE1), 1% (GAE2) or 2% (GAE3) for 8 weeks. RESULTS: After the experimental period, GAE-supplemented groups were significantly lower than the HD group in body weight gain and liver weight. GAE supplemented groups were significantly lower than the HD group in both epididymal and mesenteric adipose tissue mass. The plasma leptin level was significantly higher in the HD group than in GAE-supplemented groups. The leptin level of HD+GAE3 group was significantly lower than that of the HD+conjugated linoleic acid (CLA) group. In contrast, plasma adiponectin level of the HD group was significantly lower than those of HD+GAE2 and HD+GAE3 groups. The expression levels of adipogenic proteins such as fatty acid synthase, sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor ${\gamma}$, and CCAAT/enhancer binding protein ${\alpha}$ in the GAE supplemented groups were significantly decreased than those in HD group, respectively. In addition, the expression levels of HD+GAE2 and HD+GAE3 groups are significantly decreased compared to those of HD+CLA group. On the contrary, the expression levels of hormone-sensitive lipase and phospho-AMP-activated protein kinase, proteins associated with lipolysis, were significantly increased in the GAE supplemented groups compared to those in the HD group. HD+GAE3 group showed the highest level among the GAE supplemented groups. CONCLUSIONS: These results suggested that GAE supplementation stimulated the expressions of lipid metabolic factors and reduced weight gain in HD-fed C57BL/6J obese mice.
Objectives: In this study, the lipolytic effects of Eriobotrya folium extract (EFE) on local fat was investigated in high fat diet (HFD)-induced obesity mouse and 3T3-L1 adipocytes. Methods: C57BL/6J mice (5 weeks) were fed HFD for 6 weeks to induce obesity. EFE (20 mg/ml, $100{\mu}l$) or saline ($100{\mu}l$) as a normal control was injected into left inguinal fat pad region, 3 times per a week for last 2 weeks. After sacrifice, body weight, and histological changes of the inguinal fat pad were evaluated. The expressions of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) in inguinal fat pad were analyzed by Western blotting. Also, lipid accumulation and lipases release were determined in 3T3-L1 adipocytes by oil red o staining. Results: EFE significantly reduced the weight of inguinal fat pad and the size of adipocytes in HFD-induced obesity mice compared to control. The treatment of EFE up-regulated the expressions of HSL and ATGL in inguinal fat pads of obesity mice, as well as 3T3-L1 adipocytes. In addition, EFE inhibited the lipid accumulation in 3T3-L1 adipocytes in a dose dependent manner. Conclusions: EFE showed lipolytic effect on local fat of HFD-induced obesity mice by up-regulation of the lipases secretion. This suggests that EFE could be considered as anti-obese substance with lipolytic property on local fat.
Lee, Na-Eun;Park, Sang-Deuk;Hwang, Hongik;Choi, Sun-Hye;Lee, Ra Mi;Nam, Sung Min;Choi, Jong Hee;Rhim, Hyewhon;Cho, Ik-Hyun;Kim, Hyoung-Chun;Hwang, Sung-Hee;Nah, Seung-Yeol
Journal of Ginseng Research
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v.44
no.1
/
pp.168-177
/
2020
Background: Ginseng has been widely used as a health-promoting tonic. Gintonin present in ginseng acts as a lysophosphatidic acid (LPA) receptor ligand that activates six LPA receptor subtypes. The LPA6 subtype plays a key role in normal hair growth, and mutations in the LPA6 receptor impair normal human hair growth. Currently, human hair loss and alopecia are concerning issues that affect peoples' social and day-to-day lives. Objective: We investigated the in vitro and in vivo effects of a gintonin-enriched fraction (GEF) on mouse hair growth. Methods: Human hair follicle dermal papilla cells (HFDPCs) and six-week-old male C57BL/6 mice were used. The mice were divided into the four groups: control, 1% minoxidil, 0.75% GEF, and 1.5% GEF. The dorsal hair was removed to synchronize the telogen phase. Each group was treated topically, once a day, for 15 days. We analyzed hair growth activity and histological changes. Results: GEF induced transient [Ca2+]i, which stimulated HFDPC proliferation and caused 5-bromo-2'-deoxyuridine (BrdU) incorporation in a concentration-dependent manner. GEF-mediated HFDPC proliferation was blocked by the LPA receptor antagonist and Ca2+ chelator. HFDPC treatment with GEF stimulated vascular endothelial growth factor release. Topical application of GEF and minoxidil promoted hair growth in a dose-dependent manner. Histological analysis showed that GEF and minoxidil increased the number of hair follicles and hair weight. Conclusion: Topical application of GEF promotes mouse hair growth through HFDPC proliferation. GEF could be one of the main components of ginseng that promote hair growth and could be used to treat human alopecia.
Embryonic stem cells(ES cells) are derived from the inner cell mass(ICM) of blastocysts, which have the potentials to remain undifferentiated, to proliferate indefinitely in vitro, to differentiate into the derivates of three embryonic germ layers. ES cells are an attractive model system for studying the initial developmental decisions and their molecular mechanisms during embryogenesis. Additionally, ES cells of significant interest to those characterizing the various gene functions utilizing transgenic and gene targeting techniques. We investigated the effects of reproductive hormones, gonadotropins(GTH) and steroids on the induction of differentiation and expressions of their receptor genes using the newly established mouse ES cells. We collected the matured blastocysts of inbred mice C57BL/6J after superovulation and co-cultured with mitotically inactivated STO feeder cells. After 5 passages, we confirmed the expression alkaline phosphatase(Alk P) activity and SSEA-1, 3, 4 expressions. The protocol devised for inducing ES differentiation consisted of an aggregation steps, after 5 days as EBs in hormone treatments(FSH, LH, E$_2$, P$_4$, T) that allows complex signaling to occur between the cells and a dissociation step, induced differentiation through attachment culture during 7 days in hormone treatments. Hormone receptors were not increased in dose-dependent manner. All hormone receptors in ES cells treated reproductive hormones were expressed lower than those of undifferentiated ES cell except for LHR expression in E$_2$-treated ES cells group. After hormone induced differentiation, at least some of the cells are not terminally differentiated, as is evident from the expression of Oct-4, a marker of undifferentiated. To assess their differentiation by gene expression, we analyzed the expression of 7 tissue-specific markers from all three germ layers. Most of hormone-treated group increased in the expression of gata-4 and $\alpha$ -fetoprotein, suggesting reproductive hormone allowed or induced differentiation of endoderm.
Kim, E.Y.;Kim, S.E.;Uhm, S.J.;Yoon, S.H.;Park, S.P.;Chung, K.S.;Lim, J.H.
Clinical and Experimental Reproductive Medicine
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v.23
no.1
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pp.25-32
/
1996
This work has been carried out to examine the number of Total, ICM and TE cells of F1 mouse blastcysts at day 4 after IVF by differential labelling of the nuclei with polynucleotide-specific fluorochromes and to obtain a fundamental information of preimplantation mouse embryo development. Blastocysts produced by superovulated B6CBA F1(C57BL/${\times}$CBA) eggs were inseminated with $1{\times}10^6$spermatozoa/ml and cultured in M16 medium at $37^{\circ}C$, 5% $CO_2$ incubator for 95hrs. Blastocysts were classified as early, middle, expanded and hatching stage according to the developmental morphology; blastocoel expansion and zona thickness. The results obtained in these experiments were summarized as follows; 1) The development rate of blastocysts at 95hrs after IVF was 86.7% and classified blastocysts to early, middle, expanded and hatching were 16.3%, 18.9%, 10.5% and 40.9%, respectively. 2) The numbers of total blastomere using bisbenzimide in the classified blastocysts to early, middle, expanded and hatching were 35.6${\pm}$1O.4, 49.4${\pm}$8.6, 60.8${\pm}$1O.7 and 62.7${\pm}$13.9, respectively. 3) In ICM and TE cell number by using differential labelling with polynucleotide-specific fluorochrome in the classified blastocysts to early, middle, expanded and hatching; ICM numbers were 9.6${\pm}$3.0, 13.6${\pm}$3.9, 16.0${\pm}$3.3 and 19.5${\pm}$4.6, respectively and TE cell numbers were 30.6${\pm}$5.1, 39.9${\pm}$5.8, 42.2${\pm}$8.1 and 43.7${\pm}$11.1, respectively. These results showed the same increase pattern according to development advance level. Also, when compared with the results of total count were obtained between bisbenzimide only and differential labelling, both of them showed the same increase pattern according to development level and at the same time their cell numbers were almost the same. So, rapid and simple cell count method using differential labelling can be used for the examination of later preimplantation development or as an indicator of embryo quality according to the variables of culture conditions.
Jung, Eun Young;Hong, Yang Hee;Park, Chung;Suh, Hyung Joo
Nutrition Research and Practice
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v.10
no.2
/
pp.154-160
/
2016
BACKGROUND/OBJECTIVE: We examined the hypoglycemic and anti-hyperlipidemic effect of yeast hydrolysate (YH) enriched with Cyclo-His-Pro (CHP) in the C57BL/6J ob/ob mouse model. MATERIALS/METHODS: Mice were separated into 4 groups (8 mice/group) on the basis of blood glucose and body weight: WT control, lean mice given vehicle; ob/ob control, ob/ob mice given vehicle; YH-1, ob/ob mice given 0.5 g/kg of YH; YH-2, ob/ob mice given 1 g/kg of YH. YH in saline or vehicle was administered orally in the same volume every day for 3 weeks. RESULTS: Mice treated with YH (0.5 and 1 g/kg) for 3 weeks displayed a significant reduction in overall body weight gain and perirenal and epididymal adipose tissue weight compared to the ob/ob control group. Additionally, high-density lipoprotein (HDL) cholesterol, glucose, and atherogenic indexes were significantly decreased in the blood of YH-1 and YH-2 groups compared to the ob/ob control. In ob/ob mice, YH administration significantly improved glucose tolerance and blood insulin levels. These data indicate that YH treatment produces potent hypoglycemic and anti-hyperlipidemic effects by controlling body weight, fat mass, blood lipid, insulin levels, and glucose tolerance. CONCLUSION: YH could potentially be used as a treatment option for diabetes and hyperlipidemia. The CHP-enriched YH may be a promising strategy in the development of hypoglycemic peptide nutraceuticals.
Objectives : Peroxynitrite $(ONOO^-)$, superoxide anion radical $({\cdot}O_2^-)$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, and $({\cdot}O_2^-)$ scavenging and anti-inflammatory activities of Mori Fructus in ob/ob mice. Methods : Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups received the standard chow. The experimental groups were fed a diet of chow supplemented with 7.5, 15 and 30 mg Mori Fructus per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho $I{\kappa}B-\alpha$, anti-IKK-$\alpha$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2 and anti-iNOS respectively. Results : Mori Fructus inhibited the generation of $ONOO^-$, NO and $({\cdot}O_2^-)$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondria in vitro. The generation of $ONOO^-$, NO and $({\cdot}O2^-)$ were inhibited in the Mori Fructus-administered ob/ob mice groups. The GSH/GSSG ratio decreased in the ob/ob mice, whereas they improved in the Mori Fructus-administered groups. Mori Fructus inhibited the expression of phospho $I{\kappa}B-\alpha$, IKK-$\alpha$, COX-2, iNOS genes, and thereby the activation of NF-$I{\kappa}B$. Conclusions : These results suggest that Mori Fructus is an effective $ONOO^-$, $({\cdot}O_2^-)$ and NO scavenger, and therefore it might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.
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