• Archives of Pharmacal Research
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• v.29 no.8
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• pp.666-676
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• 2006

Gangliosides are widely distributed in mammalian cells and play important roles in various functions such as cell differentiation and growth control. In addition, diabetes and obesity cause abnormal development of reproductive processes in a variety of species. However, the mechanisms underlying these effects, and how they are related, are not fully understood. This study examined whether the differential expression of gangliosides is implicated in the abnormal follicular development and uterine architecture of streptozotocin (STZ)-induced and db/db diabetic mice. Based upon the mobility on high-performance thin-layer chromatography, mouse ovary consisted of at least five different ganglioside components, mainly gangliosides GM3, GM1, GD1a and GT1b, and diabetic ovary exhibited a significant reduction in ganglioside expression with apparent changes in the major gangliosides. A prominent immunofluorescence microscopy showed a dramatic loss of ganglioside GD1a expression in the primary, secondary and Graafian follicles of STZ-induced and db/db diabetic mice. A significant decrease in ganglioside GD3 expression was also observed in the ovary of db/db mice. In the uterus of STZ-induced diabetic mice, expression of gangliosides GD1a and GT1b was obviously reduced, but gangliosides GM1, GM2 and GD3 expression was increased. In contrast, the uterus of db/db mice showed a significant increase in gangliosides GM1, GD1a and GD3 expression. Taken together, a complex pattern of ganglioside expression was seen in the ovary and uterus of normoglycemic ICR and $db/^+$ mice, and the correspoding tissues in diabetic mice are characterized by appreciable changes of the major ganglioside expression. These results suggest that alterations in ganglioside expression caused by diabetes mellitus may be implicated in abnormal ovarian development and uterine structure.

• Journal of the Korean Society of Radiology
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• v.13 no.5
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• pp.729-737
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• 2019

Fatty pancreas is an abnormal process of lipid deposition in cells, resulting in increased fat tissue and obesity. The result is a risk factor for cardiovascular and metabolic diseases. The aim of this study was to evaluate the usefulness of pancreatic fat as a predictor of cardiovascular disease and metabolic syndrome in pancreatic ultrasonography. In 407 patients who underwent a comprehensive screening at the W Health Care Center in Busan from September 2. 2018 to December 31, 2018, the degree of fat deposition in the pancreas was evaluated as the degree of mild, moderate. Data on non-obstructive atherosclerosis, BMI, hyperlipidemia, hypertension, and diabetes were collected to assess the association of pancreatic fat deposition with cardiovascular disease and metabolic syndrome. In addition, we tried to analyze the correlation between liver dysfunction and thyroid dysfunction as the degree of fat pancreas increased. We examined the relationship between six parameters including atherosclerosis, BMI, hyperlipidemia, hypertension, diabetes, liver dysfunction, and thyroid dysfunction among patients with fatty pancreas. We concluded that the carotid intima-media thickness of atherosclerosis, which is a risk factor of cardiovascular disease, is most closely related to fatty pancreas.

• Korean Journal of Plant Resources
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• v.29 no.1
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• pp.1-10
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• 2016

Obesity is a pro-inflammatory state that contributes to the development of metabolic disorders such as hyperlipidemia, insulin resistance, type 2 diabetes, non-alcoholic fatty liver, and cardiovascular disease. In this study, we evaluated the inhibition of adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice by Peucedanum japonicum Thunberg L. water extract (PJT). Lipid accumulation measurement indicates that PJT markedly inhibited adipogenesis in a dose-dependent manner. RT-PCR results demonstrated that the mRNA expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α (C/EBPα) in 3T3-L1 cells were significantly down-regulated by PJT treatment. Oral administration of PJT (100, 300, and 500 ㎎/㎏, b.w/daily for 4 weeks) was conducted in high-fat diet induced obese mice and C57BL/6 mice. The PJT-administered group of HFD-induced mice had a lower body weight gain, along with decreased serum levels of glucose, triglycerides, and total cholesterol compared with the control mice, however, the HDL-cholesterol/total cholesterol ratio was increased. Furthermore, the elevated mRNA expression levels of adipogenesis related genes in the white adipose tissue of obese mice were significantly suppressed by PJT. These results indicate that PJT exhibits anti-obesity effects in obese mice by decreasing in serum lipid levels and lipogenesis related gene.

• Microbiology and Biotechnology Letters
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• v.44 no.1
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• pp.89-97
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• 2016

Obesity is caused by excess accumulation of body fat and contributes to various pathological disorders such as diabetes, hypertension, cardiovascular disease, and cancer. In this study, we investigated the effect of a 30% ethanol extract of Fructus Rosae laevigata (RLE) on adipogenesis in 3T3-L1 adipocytes, measured by triglyceride accumulation and expression of adipogenesis-related transcription factors during differentiation of pre-adipocytes into adipocytes. RLE decreased the intracellular triglyceride contents (assessed by Oil Red-O staining) in a dose-dependent manner. It also downregulated the expression of adipogenic transcription factors and inhibited cell proliferation during the mitotic clonal expansion phase of adipocyte differentiation by inducing G1 phase arrest. We investigated the alterations in the levels of G1 phase arrest-related proteins. The expression of p21 protein significantly increased, while the levels of Cyclin E, Cdk2, and phospho-Rb decreased in a dose-dependent manner in 3T3-L1 cells treated with RLE. These results suggest that RLE inhibits the differentiation of 3T3-L1 adipocytes by suppressing the expression of adipogenic transcription factors and inducing G1 phase arrest in the early stages of adipocyte differentiation.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3595-3604
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• 2015

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1202-1209
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• 2008

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, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the effects of Ojunghwan on the generation of peroxynitrite ($ONOO^-$), nitric oxide (NO) and superoxide anion radical (${\cdot}\;{O_2}^-$), and on the expression of $NF-{\kappa}B$-dependent inflammatory proteins in ob/ob mice. 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 have received the standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Ojung-hwan 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 blot was performed using anti-phospho $I{\kappa}B-{\alpha}$, $anti-IKK-{\alpha}$, $anti-NF-{\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-VCAM-1 and anti-MMP-9 antibodies, respectively. Ojunghwan inhibited the generation of $ONOO^-$, NO and ${\cdot}\;{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}\;{O_2}^-$ and $PGE_2$ were inhibited in the Ojunghwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas that were improved in the Ojunghwan-administered groups. Ojunghwan inhibited the expression of $phospho-I{\kappa}B-{\alpha}$, $IKK-{\alpha}$, $NF-{\kappa}B$ (p50, p65), COX-2, iNOS, VCAM-1 and MMP-9 genes. These results suggest that Ojunghwan is an effective scavenger of $ONOO^-$, ${\cdot}\;{O_2}^-$, NO and $PGE_2$, and has an inhibitory effect on the expression of $NF-{\kappa}B$-dependent inflammatory genes in ob/ob mice. Therefore, Ojunghwan might be used as a potential therapeutic drug against the inflammation process and inflammation- related diseases.

• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1152-1156
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• 2009

Silent information regulator 2 (Sir2) or sirtuins are NAD(+)-dependent deacetylases, which hydrolyze the acetyllysine residues. In mammals, sirtuins are classified into seven different classes (SIRT1-7). SIRT1 was reported to be involved in age related disorders like obesity, metabolic syndrome, type II diabetes mellitus and Parkinson’s disease. Activation of SIRT1 is one of the promising approaches to treat these age related diseases. In this study, we have used HipHop module of CATALYST to identify a series of pharmacophore models to screen SIRT1 enhancing molecules. Three molecules from Sirtris Pharmaceuticals were selected as training set and 607 sirtuin activator molecules were used as test set. Five different hypotheses were developed and then validated using the training set and the test set. The results showed that the best pharmacophore model has four features, ring aromatic, positive ionization and two hydrogen-bond acceptors. The best hypothesis from our study, Hypo2, screened high number of active molecules from the test set. Thus, we suggest that this four feature pharmacophore model could be helpful to screen novel SIRT1 activator molecules. Hypo2-virtual screening against Maybridge database reveals seven molecules, which contains all the critical features. Moreover, two new scaffolds were identified from this study. These scaffolds may be a potent lead for the SIRT1 activation.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.67 no.4
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• pp.305-318
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• 2022

To minimize the effects of aging-related comorbidities and to maintain a good quality of life and physical independence for a longer period, the improvement of lifestyle and dietary habits is essential, and healthy foods can be helpful. Among them, medicinal plant such as ginseng (Panax ginseng) and bellflower (Platycodon grandiflorum) contain natural functional substances and have been used for disease treatment and prevention since ancient times. This review summarizes the scientific of these treatments basis by investigating the pharmacological and pharmacokinetic effects of major functional substances on the aging-related health effects of Panax ginseng and Platycodon grandiflorum. The main functional substances of Panax ginseng and Platycodon grandiflorum are saponins, which have a similar molecular structure and confirmed anti-inflammatory, antioxidant, neuroprotective, anticancer, and anti-metabolic syndrome effects (improvement of hypertension, dyslipidemia, diabetes, and obesity). Both types of saponins in Panax ginseng (Ginseonside) and Platycodon grandiflorum (Platycoside) have very low absorption profiles in their purified state, but methods to increase absorption in the body through extraction or fermentation have been studied.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.3
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• pp.167-173
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• 2023

This study assesses the urine microalbumin to urine creatinine ratio (uACR) with uric acid and the association with the high-density lipoprotein cholesterol (UA/HDL-C) ratio in Korean adults. Data from the 2019 Korean National Health and Nutrition Examination Survey was procured and included 5,845 adults aged 20 years or older. Several key findings were obtained in the present study. After adjusting for the related variables (age, gender, hypertension, obesity, type 2 diabetes mellitus, and chronic kidney disease), the uACR was found to be positively associated with the quartiles of the UA/HDL-C ratio (P=0.002). Moreover, after adjusting for related variables, the odds ratio (OR) of albuminuria (uACR≥30.0 mg/g) was not significant in quartile 2 (Q2) (OR, 1.015; 95% confidence interval [CI], 0.757~1.361) and Q3 (OR, 1.090; 95% CI, 0.811~1.465) but was significantly higher in Q4 (OR, 1.416; 95% CI, 1.044~1.921) as compared to Q1 of the UA/HDL-C ratio. We conclude that since the UA/HDL-C ratio is positively associated with albuminuria in Korean adults, an increased UA/HDL-C ratio could be applied as a useful measure to assess albuminuria in Korean adults.

• Clinical and Experimental Pediatrics
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• v.48 no.5
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• pp.481-487
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• 2005

Purpose : Adiponectin, adipose tissue-specific protein, has anti-inflammatory and anti-atherogenic properties. It has been found to have a negative correlation with obesity and to play a role in modulating glucose tolerance and insulin sensitivity. Serum adiponectin concentrations are decreased in adults with obesity and type 2 diabetes. We investigated the difference in adiponectin levels between obese and non-obese children, and evaluated the relationship of serum adiponectin with body mass index(BMI), serum fasting insulin, lipid profiles and homeostasis model assessment(HOMA) in children. Methods : We measured serum adiponectin levels by radioimmunoassay in 113 children(82 obese children and 31 non-obese controls) from 8 to 15 years of age, and also checked BMI, fasting serum glucose, insulin and lipid profiles. Fasting and postprandial serum adiponectin concentrations were compared by oral glucose tolerance tests in 27 obese children. The correlations of adiponectin with BMI, insulin, low density lipoprotein(LDL)-cholesterol and HOMA were analyzed by Pearson's correlation. Results : The serum adiponectin levels were significantly lower in the obese group(19.7 mg/mL) than in the non-obese group(27.5 mg/mL)(P<0.01). Serum adiponectin concentrations were negatively correlated with BMI(r=-0.39, P<0.01), serum insulin(r=-0.28, P<0.01), LDL-C(r=-0.20, P<0.01) and HOMA(r=-0.22, P<0.01). At oral glucose tolerance tests in obese children, postprandial 2 hours adiponectin level(19.8 mg/mL) was decreased compared to fasting level(25.8 mg/mL)(P<0.01). Conclusion : Serum adiponectin concentrations were inversely related to adiposity and insulin resistance in children. We suggest the serum adiponectin level could be used as an early marker of insulin resistance in obese children.