• The Korean Journal of Physiology and Pharmacology
• /
• 제22권3호
• /
• pp.235-248
• /
• 2018

Ursolic acid (UA) is a natural triterpene compound found in various fruits and vegetables. There is a growing interest in UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects. It exerts these effects in various tissues and organs: by suppressing nuclear factor-kappa B signaling in cancer cells, improving insulin signaling in adipose tissues, reducing the expression of markers of cardiac damage in the heart, decreasing inflammation and increasing the level of anti-oxidants in the brain, reducing apoptotic signaling and the level of oxidants in the liver, and reducing atrophy and increasing the expression levels of adenosine monophosphate-activated protein kinase and irisin in skeletal muscles. Moreover, UA can be used as an alternative medicine for the treatment and prevention of cancer, obesity/diabetes, cardiovascular disease, brain disease, liver disease, and muscle wasting (sarcopenia). In this review, we have summarized recent data on the beneficial effects and possible uses of UA in health and disease managements.

• BMB Reports
• /
• 제49권2호
• /
• pp.111-115
• /
• 2016

Caffeine has been proposed to have several beneficial effects on obesity and its related metabolic diseases; however, how caffeine affects adipocyte differentiation has not been elucidated. In this study, we demonstrated that caffeine suppressed 3T3-L1 adipocyte differentiation and inhibited the expression of CCAAT/enhancer binding protein (C/EBP)α and peroxisome proliferator-activated receptor (PPAR)γ, two main adipogenic transcription factors. Anti-adipogenic markers, such as preadipocyte secreted factor (Pref)-1 and Krüppel-like factor 2, remained to be expressed in the presence of caffeine. Furthermore, 3T3-L1 cells failed to undergo typical mitotic clonal expansion in the presence of caffeine. Investigation of hormonal signaling revealed that caffeine inhibited the activation of AKT and glycogen synthase kinase (GSK) 3 in a dose-dependent manner, but not extracellular signal-regulated kinase (ERK). Our data show that caffeine is an anti-adipogenic bioactive compound involved in the modulation of mitotic clonal expansion during adipocyte differentiation through the AKT/GSK3 pathway.

• The Korean Journal of Physiology and Pharmacology
• /
• 제20권6호
• /
• pp.613-619
• /
• 2016

Diabetic cardiomyopathy (DCM), a serious complication of diabetes mellitus, is associated with changes in myocardial structure and function. This study sought to explore the ability of insulin-like growth factor-1 (IGF-1) to modulate DCM and its related mechanisms. Twenty-four male Wistar rats were injected with streptozotocin (STZ, 60 mg/kg) to mimic diabetes mellitus. Myocardial fibrosis and apoptosis were evaluated by histopathologic analyses, and relevant proteins were analyzed by Western blotting. Inflammatory factors were assessed by ELISA. Markers of oxidative stress were tested by colorimetric analysis. Rats with DCM displayed decreased body weight, metabolic abnormalities, elevated apoptosis (as assessed by the bcl-2/bax ratio and TUNEL assays), increased fibrosis, increased markers of oxidative stress (MDA and SOD) and inflammatory factors (TNF-${\alpha}$ and IL-$1{\beta}$), and decreased phosphorylation of Akt and glycogen synthase kinase (GSK-$3{\beta}$). IGF-1 treatment, however, attenuated the metabolic abnormalities and myocardial apoptosis, interstitial fibrosis, oxidative stress and inflammation seen in diabetic rats, while also increasing the phosphorylation levels of Akt and GSK-$3{\beta}$. These findings suggest that IGF-1 ameliorates the pathophysiological progress of DCM along with an activation of the Akt/GSK-$3{\beta}$ signaling pathway. Our findings suggest that IGF-1 could be a potential therapeutic choice for controlling DCM.

• 대한지역사회영양학회지
• /
• 제16권6호
• /
• pp.762-770
• /
• 2011

Osteoprotegerin (OPG) plays a core role in bone reformation by antagonizing the effect of receptor activator of nuclear factor ${\kappa}$-B ligand (RANKL), and mediates vascular calcification in cardiovascular disease patients. Thus, we aimed to examine the relationship between serum OPG levels and cardiovascular factors and inflammatory markers in metabolic syndrome patients (MS). This cross-sectional study included 96 men who visited the diet clinic between May and July 2011. Patients were classified into 2 groups based on NCEP-ATP guidelines: normal and with MS (n = 50 and 46, respectively). Physical measurements, biochemical assay were measured. Serum OPG and IL-6, diponectin and hs-CRP were assessed. MS were aged $50.02{\pm}10.85$ years, and normal patients $52.07{\pm}9.56$ years, with no significant differences. Significant differences were not observed in BMI between the 2 groups. Moreover, significant differences were not observed in serum OPG, however, the serum OPG level ($4.41{\pm}1.86pmol/L$) differed significantly between an overweight MS (BMI > 25) and normal patients. OPG was correlated to age (r = 0.410, p = 0.000), HDL-cholesterol (r = 0.209, p = 0.015), and log adiponectin (r = 0.175, p = 0.042). Multiple regression analyses using the enter method showed that age (${\beta}$ = 0.412, p = 0.000) and BMI (${\beta}$ = 0.265, p = 0.000) considerably affected OPG. In conclusion, out study showed that serum OPG levels are correlated with cardiovascular risk factors, such as BMI, HDL-cholesterol and adiponectin in MS and adiponectin, suggesting that serum OPG has potential as a cardiovascular disease indicator and predictor.

• Journal of health informatics and statistics
• /
• 제41권3호
• /
• pp.318-323
• /
• 2016

Objectives: Except the known risk factors for stroke, few studies have identified novel metabolic markers that could effectively detect stroke at an early stage. In this study, we explored the dose-response relationship between serum metabolites and the incidence of stroke. Methods: We studied 213 adults in the Korean Cancer Prevention Study-II (KCPS-II) biobank and estimated dose-response relationship between serum metabolites and stroke (42 cases and 171 controls). Three serum metabolites (Acetylcholine, HexadecylAcetylGlycerol, and 1-acetyl-2-formyl-sn-glycero-3-phosphocholine) were used in this study. The analysis included (1) exploratory nonlinear analysis, (2) estimation of flexion points and slopes at below and above the points. In the model to estimate risk of incidence of stroke, we controlled for conventional risk factors such as age, sex, systolic blood pressure, type 2 diabetes, triglyceride, and smoking status. Results: The relationship between incidence of stroke and log-transformed 1-acetyl-2-formyl-sn-glycero-3-phosphocholine was non-linear with flexion point around intensity score of 8.8, whereas other metabolites, log-transformed Acetylcholine and HexadecylAcetylGlycerol, showed negative linear patterns. Conclusions: The study suggests that metabolic markers are associated with incidence of stroke, particularly, at or above the flexion point. The study result may contribute to developing a novel system for precise stroke prediction.

• BMB Reports
• /
• 제56권11호
• /
• pp.600-605
• /
• 2023

Intrahepatic cholangiocarcinoma (ICC) is a bile duct cancer and a rare malignant tumor with a poor prognosis owing to the lack of an early diagnosis and resistance to conventional chemotherapy. A combination of gemcitabine and cisplatin is the typically attempted first-line treatment approach. However, the underlying mechanism of resistance to chemotherapy is poorly understood. We addressed this by studying dynamics in the human ICC SCK cell line. Here, we report that the regulation of glucose and glutamine metabolism was a key factor in overcoming cisplatin resistance in SCK cells. RNA sequencing analysis revealed a high enrichment cell cycle-related gene set score in cisplatin-resistant SCK (SCK-R) cells compared to parental SCK (SCK WT) cells. Cell cycle progression correlates with increased nutrient requirement and cancer proliferation or metastasis. Commonly, cancer cells are dependent upon glucose and glutamine availability for survival and proliferation. Indeed, we observed the increased expression of GLUT (glucose transporter), ASCT2 (glutamine transporter), and cancer progression markers in SCK-R cells. Thus, we inhibited enhanced metabolic reprogramming in SCK-R cells through nutrient starvation. SCK-R cells were sensitized to cisplatin, especially under glucose starvation. Glutaminase-1 (GLS1), which is a mitochondrial enzyme involved in tumorigenesis and progression in cancer cells, was upregulated in SCK-R cells. Targeting GLS1 with the GLS1 inhibitor CB-839 (telaglenastat) effectively reduced the expression of cancer progression markers. Taken together, our study results suggest that a combination of GLUT inhibition, which mimics glucose starvation, and GLS1 inhibition could be a therapeutic strategy to increase the chemosensitivity of ICC.

• Clinical Nutrition Research
• /
• 제13권1호
• /
• pp.22-32
• /
• 2024

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disorder with widespread synovitis. Isoflavones, the main active component of soy, have been reported to have potent anti-inflammatory effects; the previous RA animal models showed the promising effect of soy supplementation. We aimed to evaluate the effect of soy bread on inflammatory markers and lipid profiles in RA patients. The present study was designed as a randomized controlled trial. RA patients were randomly allocated to obtain soy bread (n = 22) or placebo bread (n = 22) for 8 weeks. Fasting serum levels of lipid profile, total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and DAS28 were checked. Findings showed that there were no significant differences between the two groups in physical activity and dietary intake at the beginning of the study and the end of the study. There were no significant differences between the two groups in measured lipid profile markers, including high-density lipoprotein, low-density lipoprotein, total cholesterol, triglyceride, and very low-density lipoprotein, at the end of the trial. In addition, TAC and CRP also were not significant at the end of the trial between the 2 groups (0.66 and 0.12, respectively). However, the serum levels of TNF-α reduced significantly in the soy bread group at the end of the intervention (p < 0.000) and compared with the control group (p < 0.019). Soy bread consumption only decreased circulating TNF-α serum concentration. Other outcome measures were not changed following supplementation. Future long-term, well-designed studies are needed to confirm these findings.

• Journal of Ginseng Research
• /
• 제35권3호
• /
• pp.301-307
• /
• 2011

To evaluate the difference in expressing pharmacological effects of ginseng by intestinal microflora between Koreans, metabolic activities of ginseng, ginsenoside $Rb_1$ and $Rg_1$ by 100 fecal specimens were measured. The ${\beta}$-glucosidase activity for p-nitrophenyl-${\beta}$-D-glucopyranoside was 0 to 0.42 mmol/min/mg and its average activity (mean${\pm}$SD) was $0.10{\pm}0.07$ mmol/min/mg. The metabolic activities of ginsenosides Rb1 and Rg1 were 0.01 to 0.42 and 0.01 to 0.38 pmol/min/mg, respectively. Their average activities were $0.25{\pm}0.08$ and $0.15{\pm}0.09$ pmol/min/mg, respectively. The compound K-forming activities from ginsenoside Rb1 and ginseng extract were 0 to 0.11 and 0 to 0.02 pmol/min/mg, respectively. Their average compound K-forming activities were $0.24{\pm}0.09$ pmol/min/ mg and $2.14{\pm}3.66$ fmol/min/mg, respectively. These activities all were not different between males and females, or between ages. Although compound K-forming activity from the aqueous extract of ginseng was low compared to that from ginenoside $Rb_1$, their profiles were similar to those of isolated compounds. Based on these findings, we believe that the intestinal bacterial metabolic activities of ginseng components are variable in individuals and may be used as selection markers for responders to ginseng.

• Genomics & Informatics
• /
• 제9권4호
• /
• pp.143-151
• /
• 2011

In this study, we propose a novel, intuitive method of constructing an expression quantitative trait (eQT) network that is related to the metabolic syndrome using LOD scores and peak loci for selected eQTs, based on the concept of gene-gene interactions. We selected 49 eQTs that were related to insulin resistance. A variance component linkage analysis was performed to explore the expression loci of each of the eQTs. The linkage peak loci were investigated, and the "support zone" was defined within boundaries of an LOD score of 0.5 from the peak. If one gene was located within the "support zone" of the peak loci for the eQT of another gene, the relationship was considered as a potential "directed causal pathway" from the former to the latter gene. SNP markers under the linkage peaks or within the support zone were searched for in the database to identify the genes at the loci. Two groups of gene networks were formed separately around the genes IRS2 and UGCGL2. The findings indicated evidence of networks between genes that were related to the metabolic syndrome. The use of linkage analysis enabled the construction of directed causal networks. This methodology showed that characterizing and locating eQTs can provide an effective means of constructing a genetic network.

• 한국자기공명학회논문지
• /
• 제10권2호
• /
• pp.126-140
• /
• 2006

Purpose: Contrary to the human study, it has rarely investigated metabolic alterations in the dorsolateral prefrontal cortex (DLPFC) of depressed rats versus age and sex-matched controls using proton magnetic resonance spectroscopy (MRS). Thus, the purpose of this research was to verify the feasibility of metabolic differences between the normal rat and the depression model rat. Materials and Methods: A homogeneous group of 20 SD male rats was used for MRI and in vivo 1H MRS. To induce a depressed status in SD rats, we performed the forced swimming test (FST). Using image-guide, water suppressed in vivo 1H MRS with 4.7 T MRI/MRS system, NAA/Cr and Cho/Cr ratios were mainly measured between depressed rats and normal subjects. Results: In depressed rats, increased Cho/Cr ratio was measured versus control subjects. However, no significant group effect for NAA/Cr was observed between case-control pairs. Discussion and Conclusions: The present 1H MRS study shows significant brain metabolic alterations of dorsolateral prefrontal cortex with experimental depressed status of SD rat induced by FST compared to normal subjects. This result provides new evidence that in vivo 1 H MRS may be a useful modality for detecting localized functional neurochemical markers alterations in left DLPFC in SD rats.