• Archives of Pharmacal Research
• /
• 제25권6호
• /
• pp.923-931
• /
• 2002

Sopungsungi-won (SP) is a known for\mula for senile constipation and diabetes mellitus, based on traditional Korean medicine. The preventive effect of SP on the development of overt diabetes in Zucker diabetic fatty (ZDF) rats was evaluated. When administered orally through a diet for 8 weeks, diabetic conditions such as hyperglycemia, polydipsia and hypertriglyceridemia were all ameliorated in SP-treated rats. In parallel with the onset and progression of hyperglycemia in the ZDF control rats; there was a marked decline in plasma insulin concentrations from 26.1 $\mu$U/ml, at age 7 weeks, to 14.8 $\mu$U/ml at age 15 weeks. In the SP-treated rats, however, the plasma insulin concentrations did not decline, and SP at a dose of 5 g/kg significantly increased the insulin levels to 31.9 $\mu$U/ml. Early normalization of plasma insulin and a retained ability to subsequently increase plasma insulin were indicative of a pancreatic $\beta$ cell protective action by the SP for\mula. In addition, expressions of an insulin-responsive gene and corresponding protein, glucose transporter 4 (GLUT4), in skeletal \muscle, were also determined in SP- and rosiglitazone-treated ZDF rats. mRNA and protein levels of GLUT4 in SP-treated rats were upregulated in a dose dependent manner. Furthermore, when ZDF rats were treated with 2 g/kg of the SP for\mula, the activity of glucose-6-phosphatase was decreased by 49%, whereas the activity of glucokinase was increased by 196%, compared to the ZDF control rats. Taken together, these data provide evidence that the SP for\mula markedly lowered the plasma glucose levels, probably through an effect not only on improvement of insulin action, but through a combined sti\mulation of glycolysis and an inhibition of gluconeogenesis in the liver, and also suggest the validity of SP's clinical use in the treatment of type 2 diabetes mellitus following further toxicological investigation.

• The Korean Journal of Physiology and Pharmacology
• /
• 제19권2호
• /
• pp.99-104
• /
• 2015

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, $C_{max}$ was $11.151{\mu}g/mL$ at 5 min after the intravenous injection and $t_{1/2}$ was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

• The Korean Journal of Physiology and Pharmacology
• /
• 제4권2호
• /
• pp.91-97
• /
• 2000

The purpose of the present study was to determine the preventive effects of combined interventional trial of fish oil treatment and exercise training on insulin resistance of skeletal muscle in high-fat fed rats. Male Wistar rats were randomly divided into chow diet (CD), high-fat diet (HF), high-fat diet with fish oil (FO), high-fat diet with exercise training (EX), and FO+EX groups. The rats in control group were fed chow diet containing, as percents of calories, 58.9% carbohydrate, 12.4% fat, and 28.7% protein. High-fat diet provided 32% energy as lard, 18% as corn oil, 27% as carbohydrate and 23% as casein. The fish oil diet had the same composition as the high fat diet except that 100 g menhaden oil was substituted for corn oil. Insulin sensitivity was assessed by in vitro glucose transport in the soleus muscle after diet treatment and treadmill running for 4 weeks. While the FO or EX only partially prevented insulin resistance on glucose transport and visceral obesity induced by high-fat diet, these interventions completely corrected hyperinsulinemia and hyperglycemia from the high-fat diet. The rats in the FO+EX showed normalized insulin action on glucose transport, plasma chemicals and visceral fat mass. Insulin-mediated glucose transport was negatively associated with total visceral fat mass (r=－0.734; p＜0.000), plasma triglyceride (r=－0.403; p＜0.05) and lepin (r=－0.583; p＜0.001) concentrations with significance. Multiple stepwise regression analysis showed that only total visceral fat mass was independently associated with insulin-mediated glucose transport (r=－0.668; p＜0.000). In conclusion, combined interventional trial of FO+EX recovered insulin resistance on glucose transport of skeletal muscle induced by high-fat diet. Visceral fat mass might be more important factor than plasma TG and leptin to induce insulin resistance on glucose transport of skeletal muscle in high-fat fed rats.

• Nutrition Research and Practice
• /
• 제8권2호
• /
• pp.177-182
• /
• 2014

BACKGROUND/OBJECTIVES: Irisin, a newly identified hormone, is associated with energy homeostasis. We investigated whether aged garlic extract (AGE) and exercise training intervention could improve body weight, insulin sensitivity, skeletal muscle fibronectin domain containing protein 5 (FNDC-5) levels, and plasma irisin in high-fat diet (HFD). MATERIALS/METHODS: Male Sprague Dawley rats were fed a ND (normal diet, n=5) or HFD (n=28) for 6 weeks. After 6 weeks, all rats were divided into 5 groups for the next 4 weeks: ND, (normal diet, n=5), HFD (high-fat diet, n=7), HFDA (high-fat diet + aged garlic extract, n=7), HFDE (high-fat diet + exercise, n=7), and HFDEA (high-fat diet + exercise + aged garlic extract, n=7). Exercise groups performed treadmill exercises for 15-60 min, 5 days/week, and AGE groups received AGE (2.86 g/kg, orally injected) for 4 weeks. RESULTS: Significant decreases in body weight were observed in the ND, HFDE, and HFDEA groups, as compared with the HFD group. Neither intervention affected the masses of the gastrocnemius muscle or liver. There were no significant differences in glucose levels across the groups. The homeostatic model assessments of insulin resistance were significantly higher in the HFD group, as compared with the ND, HFDA, HFDE, and HFDEA groups. However, skeletal muscle FNDC-5 levels and plasma irisin concentrations were unaffected by AGE or exercise in obese rats. AGE supplementation and exercise training did not affect skeletal muscle FNDC-5 or plasma irisin, which are associated with insulin sensitivity in obese rats. CONCLUSION: Our results suggest that the protection against HFD-induced increases in body fat/weight and insulin resistance that are provided by AGE supplementation and exercise training may not be mediated by the regulation of FNDC-5 or irisin.

• Journal of Yeungnam Medical Science
• /
• 제9권1호
• /
• pp.121-129
• /
• 1992

STZ투여 전후 2주씩 4주간의 규칙적인 운동 부하가 당뇨흰쥐의 골격근 당섭취와 당내성에 미치는 영향을 알아보기 위하여 Sprague-Dawley종 수컷 흰쥐를 사용하여 soleus근의 당섭취를 시험관에서 $^3H$-3-O-methyl-glucose의 섭취로 추적하였으며 정맥으로 당을 부하 (0.5g/kg BW)하여 당내성을 평가한 본 실험의 결과를 요약하면 다음과 같다. STZ의 투여로 대조군에 비하여 공복시 혈당과 유리지방산이 증가하고 인슐린 농도, soleus근의 당섭취, 인슐린에 대한 예민도와 반응도, 및 근 glycogen농도는 감소하였으며 내당능이 저하하였다. STZ 투여 흰쥐에서 4주간의 규칙적인 운동으로 인한 변화로 안정군에 비하여 공복시 혈당이 감소하고 soleus근의 당섭취와 인슐린에 대한 반응도 및 근glycogen 의 농도가 증가하였으며 유리지방산의 농도가 감소하는 경향을 보였다. 그러나 인슐린 농도는 차이가 없었으며 당내성은 개선되지 않았다. 위의 결과로 보아 4주간의 운동은 STZ 투여후 당뇨 흰쥐 발생율에는 영향을 미치지 못하였으나 골격근의 인슐린 반응도는 향상시켰으며 공복시 혈당도 감소시키는 효과를 나타내었다. 그러나 저하된 내당능은 골격근의 인슐린 반응도가 향상되었음에도 불구하고 개선되지않은 것으로 사료된다.

• Natural Product Sciences
• /
• 제28권2호
• /
• pp.68-74
• /
• 2022

HemoHIM was used as a Korean traditional medicine for anti-inflammatory and antioxidant effects. However, there is no study on the effect of HemoHIM on fatigue. We examined the potential use of HemoHIM to determine whether it can induce anti-fatigue effects. Mice were administered with HemoHIM and VEH for 14 days. On the last day of treatment, mice were subjected to behavioral tests. Subsequently, their plasma and muscle were collected after the treadmill test to measure lactate, lactate dehydrogenase (LDH), ammonia, corticosterone, glycogen, and creatine kinase (CK). We found that HemoHIM moderately increased the running time (s) in the treadmill and mobility duration in the cold swimming tests. In addition, the VEH group showed a significant increase in lactate, LDH, and corticosterone levels in the plasma compared to the group that did not perform the test. However, this was moderately reduced in HemoHIM treatment. Moreover, the HemoHIM-treated group showed significant differences in LDH and glycogen levels, and showed significantly different CK levels in the muscle. HemoHIM is considered to be effective in improving fatigue, given the duration of cold swimming or running time on a treadmill. Also, HemoHIM treatment resulted in reduced concentrations of blood and muscle parameter analysis.

• Asian-Australasian Journal of Animal Sciences
• /
• 제31권1호
• /
• pp.106-115
• /
• 2018

Objective: The goal of this study was to investigate the effects of dietary standard ileal digestible (SID) valine:lysine ratios on performance, intestinal morphology, amino acids of liver and muscle, plasma indices and mRNA expression of branched-chain amino acid (BCAA) metabolism enzymes. Methods: A total of 144 crossbred pigs (Duroc${\times}$Landrace${\times}$Large White) weaned at $28{\pm}4days$ of age ($8.79{\pm}0.02kg$ body weight) were randomly allotted to 1 of 4 diets formulated to provide SID valine:lysine ratios of 50%, 60%, 70%, or 80%. Each diet was fed to 6 pens of pigs with 6 pigs per pen (3 gilts and 3 barrows) for 28 days. Results: Average daily gain increased quadratically (p<0.05), the villous height of the duodenum, jejunum and ileum increased linearly (p<0.05) as the SID valine:lysine ratio increased. The concentrations of plasma ${\alpha}-keto$ isovaleric and valine increased linearly (p<0.05), plasma aspartate, asparagine and cysteine decreased (p<0.05) as the SID valine:lysine ratio increased. An increase in SID lysine:valine levels increased mRNA expression levels of mitochondrial BCAA transaminase and branched-chain ${\alpha}-keto$ acid dehydrogenase in the longissimus dorsi muscle (p<0.05). Conclusion: Using a quadratic model, a SID valine:lysine ratio of 68% was shown to maximize the growth of weaned pigs which is slightly higher than the level recommended by the National Research Council.

• 운동영양학회지
• /
• 제17권2호
• /
• pp.43-48
• /
• 2013

This study aims to investigate changes in plasma lipid concentrations and appetite-regulating hormone levels after a 4% body fat reduction using a 9-week intervention involving aerobic exercise, a fat-oxidizing agent, and diet limitation. After the 9-week intervention, the aerobic exercise plus hydroxycitric acid (EX+HCA), exercise (EX), and diet limitation (DIET) groups achieved the target 4% body fat reduction from the baseline value. None of the plasma lipid indicators showed significant intergroup differences, indicating that plasma lipid levels are not influenced by body weight regulation. With regard to appetite-regulating hormones, no significant intergroup differences were observed in glucose, insulin, or glucagon-like peptide-1 levels, unlike ghrelin and leptin. Ghrelin levels in particular tended to decrease in the DIET group and increase in the HCA+EX and EX groups. Leptin levels significantly decreased in the HCA+EX and EX groups, whereas no differences were observed in the DIET group. Such results indicate that exercise alone without the administration of obesity diet supplements induces elevation in ghrelin levels and reduction in leptin levels, but that diet restriction alone does not influence changes in leptin levels. Taken together, we could not confirm any synergic effects arising from the use of a fat-oxidizing agent during an exercise program to control body weight. Furthermore, diet limitation unsupported by exercise had no effect on muscle mass reduction or appetite-regulating hormone levels; thus, it is not recommended as an effective body weight control method.

• Biomolecules & Therapeutics
• /
• 제5권4호
• /
• pp.419-425
• /
• 1997

The pharmacokinetics of DWP20364 (1-cyclopropyl -5-amino-6,8-difluoro-7-(2,7-diazabiclo [3,3,0] oct-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone containing C7-bicyc-talc structure, were compared with those of ciprofloxacin (CPFX) after single intravenous (i.v.) and oral (p.o.) administration to rats using microbiological assay (bioassay). After i.v. administration to rats, the plasma concentrations of the two drugs declined biexponentially. The terminal half-lives (t$_{1}$2$\beta$/) of DWP20364 were 110$\pm$ 13.2 min and 117$\pm$3.09 min after i.v. and p.o. administration, respectively, and they were significantly higher than those of CPFX (45.5$\pm$9.52 min and 48.3$\pm$ 12.1 min, respectively). Similar results were also obtained from plasma concentrations and area under the plasma concentration-time curves. The total body clearance of DWP20364, 7.82$\pm$0.37 ml/min/kg was significantly slower than that of CPFX, 27.3 $\pm$ 11.1 m1/ min/kg. Above data suggested that the antimicrobial activity of DWP20364 could be longer than that of CPFX. The urinary recovery after i.v. and p.o. administration of DWP20364 was significantly lower than those of CPFX suggesting that the effect of DWP20364 on urinary tract infection could be lower than that of CPFX. The serum protein binding values of DWP20364 at 2$\mu$g/ml were apparently 91.5~93.1% in rats and human. DWP20364 was distributed by the order of liver, lung, kidney, sf)leon, heart, muscle and brain collected at 30 min after orally administered.

• Asian-Australasian Journal of Animal Sciences
• /
• 제20권2호
• /
• pp.229-236
• /
• 2007

This study was conducted to determine effects of different selenium (Se) sources on performance, carcass characteristics, blood measures (whole blood Se concentration and plasma glutathione peroxidase (GSH-Px) activity), and Se concentrations in tissues of finishing Hanwoo steers (Korean native steers). Twenty finishing Hanwoo steers (average body weight=536${\pm}$23.4 kg, average age=approximately 20 months) were allotted to treatments in four groups of five steers per pen for 16 weeks preceding slaughter. Treatments were control (CON), spent mushroom composts from Se-enriched mushrooms (Se-SMC), selenized yeast (Se-Y), and sodium selenite (SS). Dietary Se levels of all treatments except CON were 0.9 mg Se/kg on the dry matter basis. Body weight was measured at the first and final day of trial, and blood samples were collected to analyze whole blood Se concentration and plasma GSH-Px activity at 2, 4, 8, and 16 weeks. At the end of trial, steers were slaughtered to collect muscle and liver samples for their Se analyses, and carcass data were recorded. In terms of dry matter intake, body weight gain and carcass characteristics, no significant differences among treatments were observed. Whole blood Se concentrations were significantly higher (p<0.05) for Se-SMC and Se-Y treatments than for CON at each collection period, with no significant difference between SS and CON. For weeks 2 and 8, there was no significant difference for whole blood Se concentration between Se-SMC and Se-Y, but for weeks 4 and 16, Se-Y treatments were significantly higher (p<0.05) than Se-SMC. No differences were observed for plasma GSH-Px activity between Se-SMC and Se-Y. The Se concentrations in hind leg and liver were significantly different among treatments (p<0.05) and those in both tissues ranked the greatest in Se-Y, followed by Se-SMC, SS, and CON treatments. However, tissue Se concentration for SS was not different from that for CON. These results showed that feeding organic Se sources such as Se-SMC and Se-Y enhanced Se concentration in tissues, while SS, the most common supplement of inorganic Se, was inefficient in Se deposition. Even though Se-Y had a higher Se concentration in tissues than Se-SMC, replacing Se-Y with Se-SMC in diets of beef steers would be an inexpensive way to increase Se concentration in beef.