Peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors and their activation induces regulation of fatty acid storage and glucose metabolism. Therefore, the $PPAR\gamma$ is a major target for the treatment of type 2 diabetes mellitus. In order to generate pharmacophore model, 1080 known agonists database was constructed and a training set was selected. The Hypo7, selected from 10 hypotheses, contains four features: three hydrogen-bond acceptors (HBA) and one general hydrophobic (HY). This pharmacophore model was validated by using 862 test set compounds with a correlation coefficient of 0.903 between actual and estimated activity. Secondly, CatScramble method was used to verify the model. Hence, the validated Hypo7 was utilized for searching new lead compounds over 238,819 and 54,620 chemical structures in NCI and Maybridge database, respectively. Then the leads were selected by screening based on the pharmacophore model, predictive activity, and Lipinski's rules. Candidates were obtained and subsequently the binding affinities to $PPAR\gamma$ were investigated by the molecular docking simulations. Finally the best two compounds were presented and would be useful to treat type 2 diabetes.
Journal of the Korean Society of Food Science and Nutrition
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v.37
no.2
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pp.162-169
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2008
This study was designed to investigate the effect on treatments of garlic and the improvement of lipids in dietary-induced hyperlipidemic rats. Rats were administrated 1% cholesterol to induce hyperlipidemia and were fed diets containing fresh garlic powder (FGP), steamed garlic powder (SGP) and black garlic powder (BGP) by 3% (w/w) for 4 weeks. Body weight gain and food efficiency was not significantly different between control and garlic powder fed groups. Liver weight was significantly higher in control and SGP fed groups. Blood glucose was decreased in FGP and BGP fed groups than control group. The concentration of total lipid was significantly decreased in BGP group. Total cholesterol and triglyceride of serum were significantly lower in garlic powder fed groups than control group. HDL-cholesterol was significantly higher, LDL-, and VLDL-cholesterol were significantly lower in the garlic powder fed groups than the control group. Activities of serum GOT was lower in SGP fed group than control group. Total hepatic lipid and cholesterol concentration were conspicuously decreased by garlic powder fed groups. TBARS concentration of liver was significant different for the added garlic powder administration. Antioxidant activity of liver tended to increase in garlic powder fed groups compared with control group. In this result, we suggest the preventive effect of black garlic against the atherosclerotic process and the improvement of hyperlipidemia through the removal of cholesterol.
An, Jeong-Ran;Kang, Yeon-Kyeong;Chang, Dong-Ho;Lee, In-Seon;Shin, Soon-Shik;Jeong, Hae-Gyeong;Lee, Hee-Young;Lee, Hye-Rim
Journal of Korean Medicine Rehabilitation
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v.21
no.1
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pp.1-22
/
2011
Objectives : This study was undertaken to verify the effects of Wolbigachul-tang1(WBCEx1) on obesity using high fat diet-induced male mice and to investigate the molecular mechanisms involved. Methods : 8-week old C57BL/6 mice were divided into 5 groups; lean control, obese control, WBCEx1, 2, 3. After mice were treated with WBCEx1(water extract), 2(30% ethanol extract), 3(water extract; Ephedra sinica Stapf., Gypsum fibrosum) for 12 weeks, body weight gain, feeding efficiency ratio, plasma lipid and glucose metabolism, the messenger RNA(mRNA) expression of peroxisome proliferator activated receptor(PPAR)$\alpha$ target genes were measured. In addition, $PPAR{\alpha}$ target gene expression was examined in liver, white adipose tissue and skeletal muscle. Results : 1. WBCEx1-treated mice had significantly lower body weight gain and feeding efficiency ratio. 2. Consistent with the effects on body weight gain, WBCEx1 decreased the weights of epididymal and retroperitoneal white adipose tissue, inguinal subcutaneous adipose tissue, and brown adipose tissue. 3. WBCEx1 significantly decreased plasma triglyceride and total cholesterol levels. 4. The size of adipocytes were significantly decreased by WBCEx1, whereas the adipocyte number per unit area was increased. Hepatic lipid accumulation was decreased by WBCEx1. 5. WBCEx1 did not affect the mRNA expression of $PPAR{\alpha}$ target genes in liver, adipose tissue, and skeletal muscle. 6. Plasma asparate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatine concentrations were in the physiological range. Liver and kidney weights were significantly lower following WBCEx treatment compared with obese controls, indicating that WBCEx does not show any toxic effects on liver and kidney. Conclusions : These results suggest that WBCEx1-induced body weight reduction is associated with appetite control and mediated by a mechanism other than the activation of $PPAR{\alpha}$.
White rice consumption, a staple food for the Korean influence the other food consumption and nutrition balance. The aim of this study was to investigate the association with rice consumption based dietary intake and muscle mass for the Korean elderly who are easily in mal-nutrition. A total of 1,433 subjects (658 male and 775 female) 60 years or older from the fifth Korea National Health and Nutritional Examination Survey 2010 participated in this study. One of the findings was that there was association white rice consumption and marital status (single/with/without spouse) as well as education for men. Other interesting finding was the member of highest white rice consumption group showed higher muscle mass in both sexes. The other finding was that the more white rice consumption group showed the less meat consumption as well as the less consumption of other grains, noodle & dumpling, and flours & bread in both sexes. We found the significant association between white rice consumption level and muscle mass and several metabolic syndrome related factors in the elderly. But the association with white rice consumption and glucose metabolism related factor had not shown consistently.
This study was performed to observe the effect of hot-water extracts from garlic and 13 kinds of medicinal plants composites (GMP) on hyperlipidemia and hepatoprotective activity in rats administered with alcohol. Male Sprague-Dawly rats were fed an AIN-93 diet (Normal), a normal diet plus ethanol (control, 10 ml of 40% ethanoljkgjday), a control diet plus 0.5% garlic and 1.0% medicinal plants composites extracts (GMP-I), and a control diet plus 1.0% garlic and medicinal plants composites extracts (GMP-II) for 7 days. Blood glucose was higher than the control, but it was markedly decreased in the GMP-II group. Elevation total lipids, cholesterol, triglyceride and phospholipids in serum were markedly decreased in rats fed with GMP-I. GMP-II also inhibited the increase of lipid content in serum. Activities of GOT, GPT, $\gamma$-GTP and ALP in serum elevated by alcohol were significantly inhibited in the GMP group. TBARS content of serum was significantly decreased in GMP groups administered with garlic and medicinal plant extracts. Extracts of garlic and medicinal plants play an important role in recovering liver function in rats from alcohol induced damage.
The contribution of endogenous transport systems to the blood-brain barrier (BBB) transport of basic and acidic drugs was studied by using a carotid injection technique in rats and an isolated bovine cerebrovascular disease state were compared between the normotensive rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) which have been well established as an animal model with pathogenic similarities to humans. Basic drugs such as eperisone, thiamine and scopolamine inhibited, in a concentration dependent manner the in vivo uptake of $[{^3}H]choline$ through BBB, whereas amino acids and acidic drugs such as salicylic acid and valproic acid did not inhibit the uptake. The uptake of $[^3H]choline$ by B-CAP increased with time and showed a remarkable temperature dependency. The uptake of $[^3H]choline$ by B-CAP showed the very similar inhibitory effects as observed in the in vivo brain uptake, and was competitively inhibited by a basic drug, eperisone. The in vivo BBB uptakes of $[^3H]acetic$ acid and $[^{14}C]salicylic$ acid were dependent on pH of the injectate and the concentration of drugs. Several acidic drugs such such as salicylic acid, benzoic acid and valproic acid inhibited the in vivo uptake of $[^3H]acetic$ acid, whereas amino acid, choline and a basic drug such as eperisone did not inhibit the uptake. The uptake of acetic acid by B-CAP was competitively inhibited by salicylic acid. The permeability surface area product (PS) through BBB for $[^3H]choline$ in SHRSP was significantly lower than that in WKY. The concentration of choline in the brain dialysate in SHRSP was about half of that in WKY, while no significant difference was observed in the plasma concentration of choline between SHRSP and WKY. No significant difference was observed in the transport of monocarboxylic acids, glucose and neutral amino acid through BBB between SHRSP and WKY. From these results, it was concluded that BBB transport system of choline contributes to the transport of basic drugs through BBB, that acidic drugs can be transported via a moncarboxylic acid BBB transport system and that the specific dysfuntion of the BBB choline transport in SHRSP was ascribed to the reduction of the maximum velocity of choline concentration in the brain interstitial fluids.
Purpose: Metabolic Syndrome (MetS) is defined as a cluster of inter-connected metabolic disorders involving the glucose metabolism, dyslipidaemia, high blood pressure, and abdominal obesity. The worldwide prevalence has been rapidly increasing to approximately 20~25%, and the prevalence in Korea as of 2012 was reported to be 31.3%. The association of MetS with various diseases needs to be analyzed by conducting an investigation of frequently consumed foods, such as dairy products, fish, and shellfish in prediabetic subjects. Methods: The dietary intake of subjects who met the criteria of the study from January to December 2015 was assessed using the 24-hour recall method. After adjusting the age, sex, BMI, and total energy intake, which are confounding factors that may affect the dietary intake of the subjects, the associations of dairy products, fish, and shellfish intake with the MetS risk factors was analyzed. Results: In prediabetes, the intake of subjects who consumed more than the dairy products median (187.0 g) and the elevation risk of TC [OR, 2.369; 95% CI, 1.057 to 5.312] showed a significant positive association. In prediabetes, the intake of subjects who consumed more than the fish and shellfish median (44.0 g) and the elevation risk of BP showed a significantly weak negative association [OR, 0.073; 95% CI, 0.010 to 0.520]. The probability that the blood LDL cholesterol was ${\geq}100mg/dL$ decreased 0.397 times [95% CI, 0.189 to 0.832]. Conclusion: To control the metabolic risk factors of pre-diabetic and vascular disease subjects, proper dairy, fish and shellfish intake will be important.
The sea squirt, Halocynthia roretzi, has experienced mass mortality due to softness syndrome. The identification of disease-induced genes can provide insights into the development of this syndrome. To identify the genes, we performed differentially expressed gene (DEG) analysis. The expression of the phosphoglycerate kinase (HrPGK) gene was significantly decreased in diseased sea squirts compared to normal ones. We confirmed the result of the DEG analysis through RT-PCR and real-time PCR. In addition, we detected single nucleotide polymorphisms at position -106 (A/T) and -254 (G/T) in the HrPGK gene promoter by genotyping analysis. At the -106 site of the HrPGK gene, the frequency of the AA allele in disease-resistant sea squirts was about two-fold higher than that of sensitive ones, and the frequency of the TT allele in the disease-resistant sea squirts was about six-fold lower. At the -254 site of the HrPGK gene, the frequency of the GT and the GG allele was approximately two-fold higher and two-fold lower, respectively, in the disease-resistant sea squirts compared to the disease-sensitive ones. Analysis of the relationship between the genotypic variation at the -106/-254 promoter and the expression of HrPGK mRNA showed that HrPGK mRNA expression was higher in the -106/-254 AA/GT genotype samples than in the -106/254 TT/GG genotype ones. These results show that sea squirts harboring the AA/GT genotype may have more resistance to mortality than the sea squirts with other genotypes.
Lee, Bora;Heo, You Jung;Lee, Young Ah;Lee, Jieun;Kim, Jae Hyun;Lee, Seong Yong;Shin, Choong Ho;Yang, Sei Won
Annals of Pediatric Endocrinology and Metabolism
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v.23
no.4
/
pp.196-203
/
2018
Purpose: The hemoglobin glycation index (HGI) represents the degree of nonenzymatic glycation and has been positively associated with cardiometabolic risk factors (CMRFs) and cardiovascular disease in adults. This study aimed to investigate the association between HGI, components of metabolic syndrome (MS), and alanine aminotransferase (ALT) in a pediatric nondiabetic population. Methods: Data from 3,885 subjects aged 10-18 years from the Korea National Health and Nutrition Examination Survey (2011-2016) were included. HGI was defined as subtraction of predicted glycated hemoglobin ($HbA1_c$) from measured $HbA1_c$. Participants were divided into 3 groups according to HGI tertile. Components of MS (abdominal obesity, fasting glucose, triglycerides, high-density lipoprotein cholesterol, and blood pressure), and proportion of MS, CMRF clustering (${\geq}2$ of MS components), and elevated ALT were compared among the groups. Results: Body mass index (BMI) z-score, obesity, total cholesterol, ALT, abdominal obesity, elevated triglycerides, and CMRF clustering showed increasing HGI trends from lower-to-higher tertiles. Multiple logistic regression analysis showed the upper HGI tertile was associated with elevated triglycerides (odds ratio, 1.65; 95% confidence interval, 1.18-2.30). Multiple linear regression analysis showed HGI level was significantly associated with BMI z-score, $HbA1_c$, triglycerides, and ALT. When stratified by sex, age group, and BMI category, overweight/obese subjects showed linear HGI trends for presence of CMRF clustering and ALT elevation. Conclusion: HGI was associated with CMRFs in a Korean pediatric population. High HGI might be an independent risk factor for CMRF clustering and ALT elevation in overweight/obese youth. Further studies are required to establish the clinical relevance of HGI for cardiometabolic health in youth.
Journal of the Korean Applied Science and Technology
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v.36
no.1
/
pp.47-58
/
2019
This study aimed to investigate the improvement effect of turmeric (Curcuma longa L.) on the lipid component, protein and electrolyte concentration in dyslipidemic rats. Sprague-Dawley rats (24 male) were divided into four groups, namely the ND (normal-nondyslipidemic diet), NT (normal-nondyslipidemic diet+5% turmeric), DD (control-dyslipidemic diet), and DT groups (dyslipidemic diet+5% turmeric). Rats were sacrificed at the end of 5 weeks after experiment diet. In this study, turmeric diet (NT, DT) groups in lipid composition as evidenced from the significantly reduction of serum total cholesterol, low density lipoprotein-cholesterol (LDL-cholesterol), atherosclerotic index (AI), cardiac risk factor (CRF), triglyceride (TG), phospholipid (PL), free cholesterol, cholesteryl ester, blood glucose and non esterified fatty acid (NEFA), and elevation of high density lipoprotein-cholesterol (HDL-cholesterol) (p<0.05). The serum globulin concentration was significantly decreased (p<0.05), and the albumin concentrations were increased in turmeric diet than dyslipidemic rats. Concentrations of sodium (Na) and chlorine (Cl) in sera were lower in the DT group than DD group. Concentrations of total calcium (T-Ca), phosphorus (Pi) and potassium (K) in sera were higher in the ND, NT and DT groups than DD group. Therefore, it was concluded that the 5% turmeric diet used in the condition of this study had a beneficial effect on dyslipidemia.
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