BACKGROUND/OBJECTIVES: Obesity is a global health problem of significant importance which increases mortality. In place of anti-obesity drugs, natural products are being developed as alternative therapeutic materials. In this study, we investigated the effect of Brassica juncea L. leaf extract (BLE) on fat deposition and lipid profiles in high-fat, high-cholesterol diet (HFC)-induced obese rats. MATERIALS/METHODS: Male Sprague-Dawley rats were divided into four groups (n = 8 per group) according to diet: normal diet group (ND), high-fat/high-cholesterol diet group (HFC), HFC with 3% BLE diet group (HFC-A1), and HFC with 5% BLE diet group (HFC-A2). Each group was fed for 6 weeks. Rat body and adipose tissue weights, serum biochemical parameters, and tissue lipid contents were determined. The expression levels of mRNA and proteins involved in lipid and cholesterol metabolism were determined by reverse transcription polymerase chain reaction and western blot analysis, respectively. RESULTS: The HFC-A2 group showed significantly lower body weight gain and food efficiency ratio than the HFC group. BLE supplementation caused mesenteric, epididymal, and total adipose tissue weights to decrease. The serum levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced, and high-density lipoprotein cholesterol was significantly increased in rats fed BLE. These results were related to lower glucose-6-phosphate dehydrogenase, acetyl-coA carboxylase, and fatty acid synthase mRNA expression, and to higher expression of the cholesterol $7{\alpha}$-hydroxylase and low density lipoprotein-receptor, as well as increased protein levels of peroxisome proliferator-activated receptor ${\alpha}$. Histological analysis of the liver revealed decreased lipid droplets in HFC rats treated with BLE. CONCLUSIONS: Supplementation of HFC with 3% or 5% BLE inhibited body fat accumulation, improved lipid profiles, and modulated lipogenesis- and cholesterol metabolism-related gene and protein expression.
As obesity is known to be related to hyperlipidemia, insulin and leptin resistance, and other chronic diseases, much recent research has focused on functional food materials and their anti-obesity activity. This study was performed to study the effects of Artemisia Iwayomogi oligosaccharide AIPI on the anti-obesity function in normal rats and diet-induced obese (DIO) rats. F344 male rats were divided into four groups: Normal-control (CONT), normal-AIPI, DIO-CONT and DIO-AIPI. The groups were provided with water (in the CONT groups) or another drink for 4 weeks. The final body weights of rats in the DIO-AIPI group were lower than those in the CONT group. Abdominal adipose tissue weight per kg of body weight in the DIO-AIPI group was significantly lower than that in the DIO-CONT group. Also, the final levels of serum-triglyceride, serum-total cholesterol and serum-low density lipoprotein cholesterol in the DIO-AIPI group were lower than those in the DIO-CONT group. Moreover, the serum-high density lipoprotein cholesterol level in the normal-AIPI group was significantly higher than that in the normal-CONT group. Finally, the serum-leptin concentration was significantly lower in the DIO-AIPI group. Total lipid, triglyceride, and total cholesterol contents in the feces of the DIO-AIPI group were as high as 142%, 199%, and 165% of the respective values of the DIO-CONT GROUP. These results indicate that orally administered Artemisia Iwayomogi oligosaccharide not only has hypotriglycemic and hypocholesterolemic effects, but also has the effect of reducing the body weight and the abdominal adipose tissue weights obese rats. Therefore, we expect that Artemisia Iwayomogi oligosaccharide AIPI may have an anti-obesity function in F344 diet-induced obese rats. (Korean J Nutrition 36(5): 437∼445, 2003)
We investigated the hypoglycemic effect of formula containing Euonymus alatus (EA) and Mori Folium (MF) in multiple low dose (MLD) streptozotocin (STZ)-induced diabetic rats. In order to iduce hyperglycemic state 25 mg/kg of STZ was injected intraperitoneally for 5 consecutive days. SD rats were randomly divided into diabetic control and treatment groups. Treatment groups were administered with either 250 mg/kg of EA and 250 mg/kg of MF (E1Ml), or 500 mg/kg of EA mixed with same dose of MF (E2M2) for 3 weeks. Blood glucose levels and body weights were measured every 5th or 6th day. E1Ml and E2M2 both significantly reduced food intake, water intake, and fasting blood and urine glucose levels as compared to those in diabetic control group in a dose dependent manner. Body weight in diabetic control group was increased slightly after 3 weeks. Treatment group, however, showed gradual increase in body weights during 3 week-period. While plasma insulin levels of the diabetic control group were decreased to the level of 387$\pm$14 pg/ml from 534$\pm$36 pg/ml, those levels in E1Ml and E2M2-treated groups were both markedly increased by 13% and 26%, respectively. Urine glucose levels in E1Ml and E2M2-treated groups were also remarkably reduced by 17 and 26% compared to the levels of diabetic control group. While expression of membrane-bound glucose transporter-4 (GLUT-4) protein in skeletal muscle was reduced by 45% in diabetic control compared to the normal control, GLUT-4 protein expressions in E1Ml and E2M2-treated groups were augmented by 2 and 3.5 times compared to the diabetic control, respectively. Pancreatic HE staining experiments showed that E2M2-treated group revealed much less infiltrated mononuclear cells, indicating that E2M2 efficiently blocked insulitis induced by multiple low dose streptozotocin. Taken together, we conclude that formula containing EA and MF may prevent or delay the development of hyperglycemia through overexpression of GLUT-4 protein in skeletal muscle and prevention of insulitis.
The study was designated to investigate the gross findings following treatment with diethylnitrosamine (DEN) in rats. Forty four male rats (Sprague Dawley), initially 5 to 6 weeks of age and 120 to 150gm in body weight were continuously given water containing 0.01% DEN for 13 weeks and 3~6 rats per week were randomly sacrified at intervals of a week from 8 weeks to 17 weeks. The numbers of rats died until 17 weeks were 11 rats and first death occurred at 10 weeks. Body, liver and spleen weights were weighed and the relative weight levels of the liver and spleen per body weights were increased from 4.4% and 0.5% at control groups to 15.1% and 1.1% at 17 weeks. The numbers of RBC were not varied but PCV were decreased from 44.5% in control group to 27.5% in 16 weeks. A few of greyish-white foci or nodules of tumors were developed or not on the surfaces of the livers at 8 weeks but were developed on all livers after 9 weeks. The diameter of the largest tumor from all rat livers was 35.8 mm at 12 weeks. The numbers of developed tumors per a rat liver were appeared to be about 20 in 13 weeks and about 50~60 in 17 weeks. The diameter of some larger tumors were found to be 3~9mm in 13 weeks and 7~15mm in 17 weeks and more number of tumors were developed in the visceral surfaces than in the diaphragmatic surfaces of the livers. The parenchymae of livers were fragility.
Objectives : The objectives of this study was to obtain acute information (single oral dose toxicity) of Red-Koji (Monascus purpureus 12002) Fermented Scutellariae Radix Aqueous Extracts (fSR), has been traditionally used in Korean medicine for treating various diseases including inflammatory diseases. Methods : In order to observe the 50% lethal dose (LD50), approximate lethal dosage (ALD) and target organs, fSR powders were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.). The mortality and changes on body weight, clinical signs and gross observation were monitored during 14days after single oral treatment of fSR with organ weights and histopathological observations of 12 types of principle organs. Results : After single oral treatment of fSR, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents, on the body and organ weights, clinical signs, gross and histopathological observations, except for some accidental findings. Conclusions : The results obtained in this study suggest that the LD50 and ALD of fSR in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2,000 mg/kg and can be safety used in clinics.
Journal of Physiology & Pathology in Korean Medicine
/
v.23
no.5
/
pp.993-1002
/
2009
The object of this study was to evaluate the single dose toxicity of Taeumjowui-tang(TUJWT), a polyherbal formula have been traditionally used as prevention or treatment agent for obesity, in male and female mice. Aqueous extracts of TUJWT (Yield = 10.5%) was administered to female and male ICR mice as an oral dose of 2000, 1000 and 500 mg/kg (body wt.) according to the recommendation of KFDA Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy, organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changes in the body and organ weight except for diarrhea restricted in TUJWT 2000 mg/kg treated one male mouse at 1 day after administration, and increases of popliteal lymph node weights in all TUJWT administered groups. In addition, no TUJWT-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for increases of the frequency of hypertrophy and hyperplasia of lymphoid cells in the popliteal lymph nodes in all TUJWT treatment groups with some sporadic accidental findings. These increases of popliteal lymph node weights with hypertrophy and hyperplasia of lymphoid cells were considered that related to the immune modulate effect of TUJWT not toxicological signs. The results obtained in this study suggest that the TUJWT does not cause any toxicological signs. The 50% lethal dose and approximate lethal dose of TUJWT aqueous extracts in both female and male mice were considered as over 2000 mg/kg.
Eighteen crossbred goats were selected from the Institute's goat herd to determine the changes in hormones, blood metabolites and yield and composition of milk during lactation. The blood and milk samples were collected from each goat in a heparinized vacutainer tubes at fortnightly interval for a period of 150 days. In milk samples, fat, protein and lactose contents were estimated while in blood plasma hormones viz., prolactin, GH, cortisol, insulin, $T_4$ and $T_3$ were measured using radioimmunoassay methods. The plasma concentration of prolactin, GH and cortisol were high during early lactation when the goats acquired peak milk yield. During remainder of lactation their concentration varied. The high NEFA concentration during early lactation indicated mobilization of body reserves as the body weights also decrease during early lactation. However, with the advancement of lactation, the body weights of the goats and the concentration of NEFA declined which indicated utilization of NEFA for energy yielding purposes in addition to fatty acid synthesis. The ambient temperatures did not influence plasma concentration of prolactin, GH, insulin, $T_3$ and $T_4$ during the lactation cycle. The fat content of milk varied significantly (p<0.01) but protein and lactose content of milk remains unchanged during different stages of lactation. Growth hormone was positively correlated with insulin (p<0.05) during lactation while prolactin had a positive correlation with lactose and plasma NEFA (p<0.01) and negative correlation with $T_3$ (p<0.05).
Objectives : The object of this study was to obtain acute information (single oral dose toxicity) of Scutellariae Radix Aqueous Extracts (SR; yield = 27.20%) which traditionally have been used in Korean medicine for treating various diseases including inflammatory diseases. Methods : In order to observe the 50% lethal dose ($LD_{50}$), approximate lethal dosage (ALD) and target organs, SR Aqueous Extracts were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.) according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after single oral treatment of SR according to KFDA Guidelines with organ weights and histopathological observations of 14 types of principle organs. Results : After single oral treatment of SR, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents, on the body and organ weights, clinical signs, gross and histopathological observations, except for some accidental findings. Conclusions : The results obtained in this study suggest that the $LD_{50}$ and ALD of SR in both female and male mice after single oral treatment be considered as over 2,000 mg/kg because no mortalities were detected up to 2,000 mg/kg that was the highest dose recommended by KFDA and OECD, and can be safely used in clinics.
Kim, Seong Mo;Ku, Sae Kwang;Cho, Su Yeon;Park, Soo Jin
Journal of Physiology & Pathology in Korean Medicine
/
v.26
no.5
/
pp.714-723
/
2012
The object of this study was to evaluate the effect of Bupleuri Radix, aqueous extracts of the root part of Bupleurum falcatum on the 6-n-propyl-2-thiouracil (PTU)-induced rat hypothyroidism. Aqueous extracts of Bupleuri Radix (BR; yield = 11.73%) were administered, once day for 42 days from 2 weeks before start of PTU treatment as an oral dose of 300 and 150 mg/kg (body weight), and hypothyroidism was induced by daily subcutaneous treatment of PTU 10 mg/kg for 28 days. The changes on the body weight, thyroid gland weights, serum thyroid hormone - thyroid stimulating hormone (TSH), triiodothyronine ($T_3$) and thyroxine ($T_4$), serum lipid profiles - total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride, liver antioxidant defense system - lipid peroxidation, $H_2O_2$, superoxide dismutase (SOD) and catalase (CAT), serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed with histopathology of thyroid glands. Results were compared with $LevoT_4$ 0.5 mg/kg treated rats. As results of PTU treatment, marked decreases of body weights, triglyceride contents, liver CAT activities and changes of serum thyroid hormone levels were observed with increases of serum AST, HDL contents, liver $H_2O_2$ and SOD activities and thyroid gland weight. In addition, marked hyperplasia of follicular cells with decreases of follicular colloid contents and sizes were demonstrated at histopathological inspections. However, these PTU induced hypothyroidism were dose-dependently inhibited by treatment of BR extracts, and BR extracts effectively regulated the hypothyroidism related changes on the antioxidant defense system. The results obtained in this study suggest that BR extracts have favorable effects on the thyroid hormone productions with beneficial effects on the hypothyroidism mediated by the modulatory effects on the antioxidant defense system.
Phthalate esters have possible effects on the endocrine system. Di-n-butyl phthalate (DBP) is one of the most commonly wed phthalic acid esters (PAEs). It is extensively wed as a plasticizer in elastomers, as a solvent for printing inks and resins, and as a textile lubricating agent. It is also present in the formulations of various cosmetic products. DBP has been identified as a reproductive toxicant in several animal species and also know as a endocrine disruptor. The objective of this study was to investigate the effect of DBP on developmental immune Junction wing rat pups as experimental animals. Timed-bred pregnant SD rats were orally dosed with 0, 250, 500, or 750 mg DBP/kg body weight once a day from gestational day (GD) 5 to 18 and postpartum day (PD) 3 to 18. On PD22, the dams and their pups were euthanized and examined for alteration in parameters associated to immune function. The results showed no significant changes in body weight, thymus weight, thymus and spleen cellularities, the polyclonal activation respones of splenocyte with ConA and LPS, and also the distribution of arterial blood cells and thymocyto subsets in both rat dam and pups. However DBP exposure on rat dam resulted in increases of liver weights of dam and their pups except 750 mg DBP/kg, and body and spleen weights in pups except 750 mg DBP/kg. On the other hands, distribution rates of CD8+ T cells at 500 mg DBP/kg and B cells at 750 mg DBP/kg among splenocyte subsets were significantly increased in rat pups, unlike dams. Reasons of these distribution alterations of CD8+ T cells and B cells in rat pups are under study.
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