• Journal of Nutrition and Health
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• v.44 no.4
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• pp.275-283
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• 2011

This study was conducted to evaluate the antihyperglycemic effects of three phytoestrogens, genistein, coumestrol, and enterolactone, in type 2 diabetic animals. Forty male C57BL/KsOlaHsd-db/db mice were used as a diabetic animal model. The animals were divided into four groups and fed a phytoestrogen-free AIN-76 diet (control), or one of three phytoestrogen-supplemented (3.75 mg/100 g diet) AIN-76 diets for six weeks. During the experimental period, fasting blood glucose levels were measured on week 0, 2, 5, and 6 of the experiment, and oral glucose tolerance tests were performed on the 5th week. After the experimental period, blood concentrations of HbA1c, insulin, and glucagon were measured, and hepatic glycogen content and glucose regulating enzyme activities were analyzed. Fasting blood glucose, HbA1c level, and the area under the blood glucose curve in the oral glucose tolerance test were significantly lower in all of the phytoestrogen-supplemented groups compared to the control group. Plasma glucagon levels were also significantly lower in all of the phytoestrogen-supplemented groups compared to the control group. Hepatic glycogen level was significantly higher in the coumestrol-supplemented group compared to the other groups. However, there were no significant differences in the activities of glucokinase and glucose-6-phosphatase between the groups. These results suggest that all of the three major phytoestrogens tested in the present study were effective in lowering blood glucose levels in type 2 diabetic animals. However, further studies need to be conducted to elucidate the exact mechanism for the hypoglycemic effects of phytoestrogens.

• Journal of Food Hygiene and Safety
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• v.24 no.4
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• pp.391-397
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• 2009

Carnosine is a dipeptide ($\beta$-alanyl-L-histidine) found in mammalian brain, eye, olfactory bulb and skeletal muscle at high concentrations. Its biological functions include antioxidant and anti-glycation activities. The objectives of this study were to investigate anti-diabetic effects of carnosine as determined by blood glucose levels in glucose tolerance test (GTT) and insulin tolerance test (ITT), insulin level and serum biochemical and lipid levels in male C57BL/6J db/db mice. There were five experimental groups including normal (C57BL/6J), control (vehicle), and three groups of carnosine at doses of 6, 30, and 150 mg/kg b.w. Carnosine was orally administered to the diabetic mice everyday for 8 weeks. There was no significant difference in body weight changes in carnosine-treated groups compared to the control. The treatments of carnosine significantly decreased the blood glucose level in the diabetic mice compared with the control (p < 0.05) after 5 weeks. The treatments of carnosine also significantly decreased the blood glucose levels in GTT and ITT and glycosylated hemoglobin (HbA1c), compared with the control (p < 0.05). Carnosine at the dose of 6 mg/kg significantly decreased the serum insulin level compared to the control (p < 0.05). Carnosine significantly increased total proteins but significantly decreased lactate dehydrogenase and blood urea nitrogen compared with the control (p < 0.05). Carnosine also significantly decreased glucose, LDL, and triglyceride in the serum of diabetic mice compared to the control (p < 0.05). These results suggest that carnosine has a hypoglycermic effect resulting from reduction of glucose and lipid levels and that high carnosine-containing diets or drugs may give a benefit for controlling diabetes mellitus in humans.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.302-310
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• 2018

CD47 (integrin-associated protein), a multi-spanning transmembrane protein expressed in all cells including red blood cells (RBCs) and leukocytes, interacts with signal regulatory protein ${\alpha}$ ($SIRP{\alpha}$) on macrophages and thereby inhibits phagocytosis of RBCs. Recently, we generated a novel C57BL/6J CD47 knockout ($CD47^{-/-}$ hereafter) mouse line by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease, and here report their hematological phenotypes. On monitoring their birth and development, $CD47^{-/-}$ mice were born viable with a natural male-to-female sex ratio and normally developed from birth through puberty to adulthood without noticeable changes in growth, food/water intake compared to their age and sex-matched wild-type littermates up to 26 weeks. Hematological analysis revealed a mild but significant reduction of RBC counts and hemoglobin in 16 week-old male $CD47^{-/-}$ mice which were aggravated at the age of 26 weeks with increased reticulocyte counts and mean corpuscular volume (MCV), suggesting hemolytic anemia. Interestingly, anemia in female $CD47^{-/-}$ mice became evident at 26 weeks, but splenomegaly was identified in both genders of $CD47^{-/-}$ mice from the age of 16 weeks, consistent with development of hemolytic anemia. Additionally, helper and cytotoxic T cell populations were considerably reduced in the spleen, but not in thymus, of $CD47^{-/-}$ mice, suggesting a crucial role of CD47 in proliferation of T cells. Collectively, these findings indicate that our $CD47^{-/-}$ mice have progressive hemolytic anemia and splenic depletion of mature T cell populations and therefore may be useful as an in vivo model to study the function of CD47.

• Korean Journal of Animal Reproduction
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• v.18 no.3
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• pp.191-197
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• 1994

It is generally known that mutations in any of several genes encoding photoreceptor-specific proteins have resulted in retinitis pigmentosa (RP), a disease characterized by losing photoreceptor function with progressive degeneration of photoreceptor cells and eventually leading to blindness. To study the procure and cure of photoreceptor degeneration, we produced transgenic mice. Transgene consisted of a 12.5kb genomic DNA fragment that contains mutated pig rhodopsin gene (Pro-347-Ser) including both the 5'-franking (4.0 kb) and the 3'-franking (2.9 kb) sequences. This gene was used for the production of transgenic mouse. The mutated rhodopsin DNA was microinjected into male pronuclei of fertilized mouse (C57BL /6]) embryos. We detected transgenic animals harboring mutated rhodopsin gene by PCR and Southern blot analysis. These transgenic mice showed stable transmission of microinjected rhodopsin gene into their offspring. Therefore these animals will provide a novel approach to study the mechanism of the photoreceptor degeneration and be provided as a disease model for the treatment of the blind in human.

• Korean Journal of Biological Psychiatry
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• v.15 no.2
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• pp.101-109
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• 2008

Objectives : This study was conducted to examine the effects on food intake, body weight, and metabolic parameters by amisulpride administration in male and female mice, comparing the effects of risperidone and vehicle administration. Methods : Female and male C57BL/6 mice were grouped into low dose amisulpride(1.5mg/kg), high dose amisulpride(15mg/kg), risperidone(0.1mg/kg) and vehicle. Drugs were administered once daily through intraperitoneal injection over 21days. Body weight was measured weekly and food intake was measured daily. Levels of triglyceride, glucose, insulin and prolactin were determined at the end of experiment(on day 22). Results : In the female mice, low and high dose amisulpride as well as risperidone caused significant weight gains. But weight gains in amisulpride groups were numerically smaller than that of risperidone group. In male mice, only high dose amisulpride caused significant weight gain. Among weight gain groups, only weight gain of male mice with high dose amisulpride was significantly associated with increased food intake. Weight gain group in female mice did not show significant correlation with food intake. In male mice, both amisulpride groups showed significantly high plasma insulin levels compared to vehicle. In female and male mice, low and high dose amiulpride groups showed significant high plasma prolactin levels compared to vehicle. Triglyceride level were not significantly changed in all groups. Glucose level was changed significantly only in male risperidone group. Conclusions : Administration of amisulpride caused more significant weight gains in female and male mice than controls but changes of metabolic parameters were different according to sex of mice. Our results suggest that different mechanisms of amisulpiride are likely to affect weight gain between male and female mice.

• Preventive Nutrition and Food Science
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• v.18 no.2
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• pp.104-110
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• 2013

Presence of Helicobacter pylori is associated with an increased risk of developing upper gastrointestinal tract diseases. Antibiotic therapy and a combination of two or three drugs have been widely used to eradicate H. pylori infections. Due to antibiotic resistant drugs, new drug resources are needed such as plants which contain antibacterial compounds. The aim of this study was to investigate the ability of GutGard$^{TM}$ to inhibit H. pylori growth both in Mongolian gerbils and C57BL/6 mouse models. Male Mongolian gerbils were infected with the bacteria by intragastric inoculation ($2{\times}10^9$ CFU/gerbil) 3 times over 5 days and then orally treated once daily 6 times/week for 8 weeks with 15, 30 and 60 mg/kg GutGard$^{TM}$. After the final administration, biopsy samples of the gastric mucosa were assayed for bacterial identification via urease, catalase and ELISA assays as well as immunohistochemistry (IHC). In the Mongolian gerbil model, IHC and ELISA assays revealed that GutGard$^{TM}$ inhibited H. pylori colonization in gastric mucosa in a dose dependent manner. The anti-H. pylori effects of GutGard$^{TM}$ in H. pylori-infected C57BL/6 mice were also examined. We found that treatment with 25 mg/kg GutGard$^{TM}$ significantly reduced H. pylori colonization in mice gastric mucosa. Our results suggest that GutGard$^{TM}$ may be useful as an agent to prevent H. pylori infection.

• Preventive Nutrition and Food Science
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• v.15 no.1
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• pp.19-23
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• 2010

This study examined the effects of Acrylamide (ACR) and L-ascorbic acid (AsA) on the proliferation of splenocytes and the mitogen-stimulated lymphocyte proliferation in young (8 weeks) and aged (82 weeks) C57BL/6male mice in vitro. AsA increased splenocyte proliferation in both groups; however, this effect was higher in old mice, while the proliferation of lymphocyte was decreased except for treatment at $1\;{\mu}g/mL$ low concentration in both mice. In addition, ACR treatment resulted in decreased LPS-induced B lymphocyte proliferation and ConA-induced T lymphocyte proliferation in both groups. However, AsA increased LPS/ConA-induced lymphocyte proliferation in young groups and had no effects in old mice except at $0.5\;{\mu}g/mL$ Thus, the present data indicate that there is no difference effect of ACR and AsA on lymphocyte proliferation, whereas the effect of AsA on mitogen-induced cell proliferation was reduced in old mice. Overall, our results suggest that various immunomodulators have differing effects of lymphocytic proliferation on young versus aged mice.

• Journal of Pharmacopuncture
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• v.20 no.4
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• pp.257-264
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• 2017

Introduction: Pharmacopuncture, which combines acupuncture with herbal medicine, is one of the newly developed acupuncture techniques that has recently been put into use. The possible mechanisms of scolopendra pharmacopuncture, as well as its potential effects on depressive symptoms, were investigated in this study by using a mouse model of chronic immobilization stress (CIS). Methods: C57BL/6 male mice were randomly assigned into three groups: mice not stressed with restraint and injected with distilled water, mice stressed with restraint and injected with distilled water, and mice stressed with restraint injected with scolopendra pharmacopuncture at a cervical site. Behavioral tests (an open field test, tail suspension test, and forced swimming test) were carried out after two weeks of CIS and injection treatments. The expression levels of glial fibrillary acidic protein (GFAP) in the hippocampus were determined by using western blot and immunohistochemistry analyses. Results: Mice exposed to CIS showed decreased behavioral activity, while scolopendra pharmacopuncture treatment significantly protected against the depressive-like behaviors induced by CIS. Moreover, scolopendra pharmacopuncture treatment increased GFAP protein levels in the hippocampi of the mice stressed by chronic immobilization. Conclusion: Scolopendra pharmacopuncture has an ameliorating effect on depressive behavior, which is partially mediated through protection against glial loss in the hippocampus.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.9
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• pp.1159-1165
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• 2006

Our preliminary study showed that genistein and daidzein improved blood glucose level in type 2 diabetic mice by enhancing the glucose and lipid metabolism. The objective of this study was to evaluate whether genistein and daidzein are associated with alterations in antioxidant defense mechanism of type 2 diabetic mice. Male C57BL/KsJ-db/db (db/db) mice and age-matched non-diabetic littermates (db/+) were used in this study. The db/db mice were divided into control, genistein (0.02%, w/w) and daidzein (0.02%, w/w) groups. The relative weights of liver, epididymal adipose tissue and perirenal adipose tissue were significantly higher in the db/db group than in the db/+ group, whereas heart weight was lower. The genistein and daidzein supplement did not affect the organ weights in db/db mice. The blood glucose level was positively correlated with superoxide dismutase (SOD, r=0.380, p<0.05) and catalase (CAT, r=0.345, p<0.05) activities and negatively correlated with glutathione peroxidase (GSH Px, r= 0.404, p<0.05) activity in erythrocyte. Therefore, the erythrocyte SOD and CAT activities were significantly elevated in the db/db group compared to the db/+ group and the GSH-Px activity was lowered. However, the supplementation of genistein and daidzein reversed erythrocyte CAT and GSH-Px activities in type 2 diabetic mice. In this current study, the SOD activities in liver, kidney and heart were significantly not different between the groups. The CAT and GSH-Px activities in liver and GSH-Px activity in kidney were significantly higher in the db/db group than in the db/+ group, while the CAT activity in kidney, CAT and GSH-Px activities in heart were lowered. The supplementation of genistein and daidzein significantly attenuated the changes of CAT and/or GSH-Px activities in liver and heart. The supplementation of genistein and daidzein elevated GSH levels in kidney and heart compared to the db/db control group. The lipid peroxide levels in liver, kidney and heart were significantly lowered in the genistein and daidzein supplemented groups compared to the db/db control group. These results suggest that genistein and daidzein might be beneficial for the prevention of type 2 diabetic complication via suppressing changes of antioxidant enzymes activities with simultaneous reduction of lipid peroxidation.

• Journal of Nutrition and Health
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• v.55 no.1
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• pp.36-46
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• 2022

Purpose: Quercetin is a polyphenolic flavonoid abundant in many fruits and vegetables. It has potential health-beneficial properties, such as antioxidant, anti-obesity, anti-cancer, anti-diabetic and anti-inflammatory effects. The purpose of this study was to investigate whether the lipid metabolism improvement effect of quercetin affected the regulation of AMP-activated protein kinase (AMPK) activity and microRNA (miR)-21 expression in the liver of mice fed a high-cholesterol diet. Methods: Male C57BL/6J mice were fed with normal diet, quercetin-free diet and diets containing 0.05% or 0.1% quercetin for six weeks. Hypercholesterolemia was induced by adding 1% cholesterol and 0.5% cholic acid to all diets. Serum and liver triglyceride (TG), and total cholesterol (TC) concentrations were analyzed using a commercial enzymatic colorimetric kit. AMPK activity was quantified using an AMPK kinase assay kit. The levels of miR-21 and genes involved in lipid metabolism were measured by real-time quantitative polymerase chain reaction. Results: Supplementation of quercetin reduced serum and hepatic TG and TC levels without changing body weight and food intake. Dietary quercetin significantly inhibited the mRNA levels of hepatic sterol-regulatory element binding protein-1c, acetyl-CoA carboxylase 1 and fatty acid synthesis, which are involved in hepatic lipogenesis. Dietary quercetin enhanced AMPK activity and suppressed miR-21 expression, promoting hepatic lipid accumulation. Conclusion: These results suggest that the lipid-lowering effect of quercetin on the serum and liver of mice may be partially mediated by the regulation of lipogenic gene expression, AMPK activity and miR-21 expression in the liver of mice fed a high-cholesterol diet.