[Show abstract][Hide abstract] ABSTRACT: To clarify the anti-obesity effect of Allomyrina dichotoma larvae (ADL), we previously reported that ADL block adipocyte differentiation on 3T3-L1 cell lines through downregulation of transcription factors, such as peroxisome proliferator-activated receptor-γ (PPARG) and CCAAT/enhancer binding protein-α (CEBPA). In this study, we tested whether ADL prevent obesity in mice fed a high-fat diet (HFD) and further investigated the mechanism underlying the effects of ADL. All mice were maintained on a normal-fat diet (NFD) for 1 week and then assigned to one of five treatment groups: (1) NFD; (2) HFD; (3) HFD and 100 mg·kg-1·day-1 ADL; (4) HFD and 3000 mg·kg-1·day-1ADL; or (5) HFD and 3000 mg·kg-1·day-1 yerba mate (Ilex paraguariensis, positive control). ADL and yerba mate were administered orally daily. Mice were fed experimental diets and body weight was monitored weekly for 6 weeks. Our results indicated that ADL reduced body weight gain, organ weight and adipose tissue volume in a dose-dependent manner. Body weight gain was approximately 22.4% lower compared to mice fed only HFD, but the difference did not reach the level of statistical significance. Real-time polymerase chain reaction (PCR) analysis revealed that gene expression levels of PPARG, CEBPA and lipoprotein lipase (LPL) in the epididymal fat tissue of HFD-fed mice receiving 3000 mg·kg-1·day-1 ADL were reduced by 12.4-, 25.7-, and 12.3-fold, respectively, compared to mice fed HFD only. Moreover, mice administered ADL had lower serum levels of triglycerides and leptin than HFD-fed mice that did not receive ADL. Taken together our results suggest that ADL and its constituent bioactive compounds hold potential for the treatment and prevention of obesity.
[Show abstract][Hide abstract] ABSTRACT: Although Korean horn beetle (Allomyrina dichotoma) larvae have been long used as an oriental medicine for the treatment of liver diseases in Korea, there is little scientific evidence of their effects. In this study, we investigated the anti‐obesity activity of A. dichotoma larvae extract (ADE) by using 3T3‐L1 cells as an in vitro model of adipogenesis. To analyze its role as an inhibitor of adipogenesis, 3T3‐L1 cells were treated with both ADE and differentiation inducer (DM) at the same time, and then the amount of lipid was quantified. We then analyzed the mRNA and protein expression level of adipogenic or lipogenic genes. The results showed that formation of lipid droplets in differentiated 3T3‐L1 cells was markedly decreased, and triglyceride content was reduced by 22.15% in response to 2000 μg/mL ADE. In addition, ADE downregulated mRNA and protein expression of transcription factors peroxisome proliferator‐activated receptor (PPAR)‐γ and CCAAT/enhancer binding protein (C/EBP)‐α implicated in adipogenesis, and significantly decreased the expression levels of adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), stearoyl‐coenzyme desaturase‐1 (SCD1), and lipoprotein lipase (LPL) related to lipogenesis. Our results demonstrate that ADE suppressed adipogenesis and lipogenesis in 3T3‐L1 cells, suggesting that ADE has anti‐obesity activity as a food supplement.
Entomological Research 01/2014; 44(1). DOI:10.1111/1748-5967.12044 · 0.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate Protaetia brevitarsis as a food material, we investigated its composition of nutritional and harmful components. Analysis of nutritional composition (moisture, crude protein, crude fat, crude ash, crude fiber, and carbohydrates) showed that the content of crude protein, fat, fiber, and ash were %, %, %, and % in Protaetia brevitarsis powder, respectively. Amino acids were composed of 17.68% essential and 33.97% non-essential in Protaetia brevitarsis powder. Protaetia brevitarsis powder contained 61.10% unsaturated fatty acid with oleic acids. Additionally, Protaetia brevitarsis powder had a large quantity of minerals related to body organization, such as K (1597 mg/100 g), P (724.1 mg/100 g), Mg (366.3 mg/100 g), and so on. We also confirmed that all bacteria and all heavy metals analyzed in this study, except for very small amount of Hg ( mg/kg), were not detected in the lysophilized Protaetia brevitarsis powder.
[Show abstract][Hide abstract] ABSTRACT: Although the mealworm larva (Tenebrio molitor) is high protein source, aversion feature of the larva made it difficult for consuming as a food. In this study, we established optimal powder manufacturing process for T. molitor larva for using as a novel food. For this purpose, it should be feed with the bran sterilized by water vapor for 3-5 days, starved without water or food for 3 days, and then the larvae were sterilized before freeze-drying. The sterilized T. molitor was lyophilzed and grinded by a blender. A safety of the powder as a food was validated by evaluation of Raw 264.7 macrophage cytotoxicity using MTS assay. As above results, we propose that optimal powder manufacturing process established in this study can be used in industrial production of T. molitor as a novel food.
[Show abstract][Hide abstract] ABSTRACT: With the objective of developing a functional food source, we established optimal processing conditions for the larvae of Allomyrina dichotoma, which have been used in traditional medicine to treat hepatic disorders in Korea. Without suitable processing, the larvae are difficult to consume as a food because of their disgusting taste and smell; moreover, in this form they might be a potential microbial hazard. In this study, we investigated the effect of feeding material, sterilization, and powdering after freeze-drying on the food quality of the larvae of A. dichotoma and on cytotoxicity against Raw 264.7 cells. Three to five days feeding with the sawdust from discarded oak-trees is sufficient for the breeding process. The sawdust was sterilized by vapor for five minutes. Sterilization of the larvae at a high temperature ( for 5 min, 0.9 ) is necessary to eliminate pathogenic bacteria and fungi. The results of the cytotoxicity assay showed no toxicity in the prepared extract from larvae of A. dichotoma. In addition, to prepare the larvae for human consumption, various feeds were used and the smell, color, and taste were evaluated. Our results suggested that larvae of A. dichotoma could be developed as food source when a suitable processing method is established.
[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer is rare in teenagers, especially without known risk factors. Colon cancer in young age is more likely to be diagnosed at advanced-stage, to present unfavorable tumor histology such as mucinous carcinoma, and poor outcome. We report a case of sporadic mucinous adenocarcinoma of the colon in a 19-year-old male patient without any risk factors. He complained of severe left abdominal pain that developed 1 month ago. He had a distended abdomen with severe tenderness on the left lower quadrant. A distal descending colon mass causing mechanical obstruction was observed on abdominal computed tomography. Emergency colonoscopy showed a large, fungating mass obstructing the lumen at 40 cm from the anal verge. Biopsy of the colonic mass suggested a mucinous adenocarcinoma. After decompression by colonic stent, the patient was transferred to the general surgery department for left hemicolectomy. The lesion was confirmed to be a mucinous adenocarcinoma (7.0×4.5 cm). For hereditary nonpolyposis colorectal cancer evaluation, immunohistochemical staining for MLH1 and MSH2 was normal. Reverse transcription polymerase chain reaction analysis did not detect microinstability in any of the markers tested. The patient had no familial history of cancer. Mucinous adenocarcinoma has high frequencies of poor differentiation, advanced tumor stage, loss of mismatch repair gene expression, and increased MUC2 expression. A mucinous histology is considerably more frequent in children and adolescent than in adults. Adequate invasive study is also necessary for young age patients.
[Show abstract][Hide abstract] ABSTRACT: The present study aimed to determine the role of cystatin C as a prognostic factor for acute kidney injury and survival in cirrhotic patients.
The study investigated 53 liver cirrhosis patients. The renal function was evaluated by serum creatinine, serum and urine cystatin C, and 24-hour creatinine clearance on admission. Acute kidney injury was defined as a serum creatinine level exceeding the normal range (>1.2 mg/dl) and an increase of at least 50% from the baseline value. Multivariate analysis, receiver operating characteristic curve, and survival analysis were used to investigate prognostic factors for acute kidney injury and survival.
Nine of the 53 cirrhotic patients (17.0%) developed acute kidney injury within 3 months. Both serum creatinine and cystatin C were predictive factors for acute kidney injury in univariate analysis, with a diagnostic accuracy of 0.735 (95% confidence interval (CI), 0.525-0.945; p=0.028) for serum cystatin C and 0.698 (95% CI, 0.495-0.901, p=0.063) for creatinine. In multivariate analysis, only serum cystatin C was an independent risk factor for acute kidney injury. The sensitivity and specificity of a serum cystatin C level of >1.23 mg/L to acute kidney injury were 66% and 86%, respectively. Serum cystatin C was positively correlated with the Model for End-Stage Liver Disease (MELD) and MELD-Na scores (r=0.346 and p=0.011, and r=0.427 and p=0.001, respectively). Comparison of the survival rates over the observation period revealed that a serum cystatin C level of >1.23 mg/L was a useful marker for short-term mortality (p<0.001).
The accuracy in predicting acute kidney injury and short-term mortality was higher for a serum cystatin C level of >1.23 mg/L than for the serum creatinine concentration in patients with cirrhosis.
The Korean Journal of Hepatology 09/2010; 16(3):301-7. DOI:10.3350/kjhep.2010.16.3.301
[Show abstract][Hide abstract] ABSTRACT: Inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT) is proposed to be a drug target for the treatment of obesity and type 2 diabetes. Bioassay-guided fractionation of the CH(2)Cl(2)-soluble extract of the stem bark of Erythrina senegalensis, using an in vitro DGAT enzyme assay, resulted in the isolation of eight known prenylflavonoids, 8-prenylleutone (1), auriculatin (2), erysenegalensein O (3), erysenegalensein D (4), erysenegalensein N (5), derrone (6), alpinumisoflavone (7), and 6,8-diprenylgenistein (8). Compounds 1, 2-4, 6, and 8 inhibited DGAT activity, with IC(50) values ranging from 1.1 +/- 0.3 to 15.1 +/- 1.1 microg/mL. On the basis of the data obtained, we propose isoflavonoids with isoprenyl groups as a novel class of DGAT inhibitors.
Archives of Pharmacal Research 02/2009; 32(1):43-7. DOI:10.1007/s12272-009-1116-2 · 2.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The results of previous studies suggest that portion size is a major factor dictating dietary energy intake. We investigated the relationship between frequencies of rice meals, bowl volumes, and dietary energy intake in a sample of patients with type 2 diabetes.
Korean Diabetes Journal 01/2009; 33(4). DOI:10.4093/kdj.2009.33.4.335
[Show abstract][Hide abstract] ABSTRACT: During the screening for diacylglycerol acyltransferase (DGAT) inhibitors from natural products, the lupane-type triterpenoid betulinic acid was isolated from the methanol extract of Alnus hirsuta. It potently inhibited DGAT in the rat liver microsomes with an IC (50) value of 9.6 microM. Enzyme kinetic studies showed apparent Km and Ki values of 13.3 microM and 8.1 microM using [(14)C]oleoyl-CoA as a substrate. A decrease in the apparent Vmax was observed with betulinic acid, whereas the apparent Km remained constant. Therefore, a Lineweaver-Burk plot of DGAT inhibition by betulinic acid showed a non-competitive type of inhibition. In the cell-based assay, betulinic acid inhibited triglyceride (TG) formation by human HepG2 cells. These findings suggest that betulinic acid may be a potential lead compound in the treatment of obesity.
[Show abstract][Hide abstract] ABSTRACT: Human vascular smooth muscle cells (HVSMCs) are resistant to Fas-mediated death under normal physiological conditions. However, HVSMC death by activation of the receptor pathway was reported in the atherosclerotic lesions. In this study, we investigated whether 7-ketocholesterol, one of the major cholesterol oxides in the lesions, altered resistance of HVSMC to Fas-mediated death pathway. Cross-linking of Fas receptor with agonistic anti-Fas antibody (CH11) in the presence of 7-ketocholesterol induced death in human aorta smooth muscle cells (HAoSMC) as detected by morphology, viability, and DNA fragmentation. The agonistic anti-Fas antibody, however, did not induce death in the presence of 7alpha-hydroxycholesterol or cholesterol. The HAoSMC death was significantly inhibited by an antagonistic Fas receptor (FasR) antibody and by expression of dominant negative Fas-associated death domain containing protein (DN-FADD) using adenoviruses. Activation of caspase-3 was observed in HAoSMC destined to death. HAoSMC death was significantly inhibited by pharmacological caspase inhibitor, z-VAD and z-DEVD, and baculovirus caspase inhibitor p35. 7-Ketocholesterol impaired mitochondrial transmembrane potential and ATP production. Overexpression of bcl-xL also significantly inhibited HAoSMC death. In dying HAoSMC, bax was translocated from the cytosol to mitochondria and cytochrome c was released from mitochondria into the cytosol. This is the first report demonstrating implication of the oxysterol in Fas-mediated death pathway. The present study proposes that 7-ketocholesterol would contribute to loss of HVSMC in the atherosclerotic lesions by altering resistance to receptor-mediated death pathway.
Journal of Molecular and Cellular Cardiology 12/2005; 39(5):823-32. DOI:10.1016/j.yjmcc.2005.07.018 · 4.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was undertaken to investigate whether a physiologically compatible concentration of 7-ketocholesterol had any effect on human vascular smooth muscle cells (HVSMCs). We found that 7-ketocholesterol changed the viability of human aorta smooth muscle cells (HAoSMC) not by cytotoxicity but by activation of tumor necrosis factor-alpha receptor (TNFR)-mediated death. Whereas TNF-alpha did not affect the viability in the presence of 7alpha-hydroxycholesterol or cholesterol, the cytokine induced HAoSMC death in the presence of 7-ketocholesterol as detected by morphology, viability, and fragmentation of chromosomal DNA. The HAoSMC death was inhibited by a neutralizing anti-TNF receptor 1 (TNFR1) antibody and by the caspase inhibitors of z-VAD and z-DEVD. Activations of caspase-8 and -3 were detected from dying HAoSMCs. 7-Ketocholesterol inhibited translocation of the nuclear factor kappaB (NF-kappaB) subunits of p65 and p50 from the cytosol into the nucleus, increase of NF-kappaB activity, and expression of caspase-8 homolog Fas ligand interleukin-1-converting enzyme inhibitory protein by TNF-alpha. We also found that X-chromosome-linked inhibitor of apoptosis protein was degraded in dying HAoSMC. The present study proposes that 7-ketocholesterol would contribute to the disappearance of HVSMC in the atherosclerotic lesions by enhancing receptor-mediated death. This is the first report demonstrating induction of TNF-alpha-mediated death by oxysterol in cells.
Biochemical and Biophysical Research Communications 09/2005; 333(4):1093-9. DOI:10.1016/j.bbrc.2005.05.196 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acyl-CoA: cholesterol acyltransferase (ACAT), which plays a role in the absorption, storage, and production of cholesterol, has been explored as a potential target for pharmacological intervention of hyperlipidemia and atherosclerotic disease. In our search for ACAT inhibitors from natural sources, the petroleum ether extract of Panax ginseng showed moderate inhibition of ACAT enzyme from rat liver microsomes. Bioactivity-guided fractionations led to the isolation of one new polyacetylenic compound, (9R,10S)-epoxy-16-heptadecene-4, 6-diyne-3-one (1), in addition to the previously reported polyacetylenic compounds 2 and 3. Their chemical structures were elucidated on the basis of spectroscopic evidence (UV, IR, NMR, and MS). The compounds 1, 2, and 3 showed significant ACAT inhibition with IC(50) values of 35, 47, and 21 microM, respectively.
Journal of Agricultural and Food Chemistry 03/2005; 53(4):919-22. DOI:10.1021/jf040370x · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Leukocyte adhesion to the vascular endothelium is a critical initiating step in inflammation and atherosclerosis. We have herein studied the effect of manassantin A (1) and B (2), dineolignans, on interaction of THP-1 monocytic cells and human umbilical vein endothelial cells (HUVEC) and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HUVEC. When HUVEC were pretreated with 1 and 2 followed by stimulation with TNF-alpha, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with IC50 values of 5 ng/mL and 7 ng/mL, respectively, without cytotoxicity. Also, 1 and 2 inhibited TNF-alpha-induced up-regulation of ICAM-1, VCAM-1 and E-selectin. The present findings suggest that 1 and 2 prevent monocyte adhesion to HUVEC through the inhibition of ICAM-1, VCAM-1 and E-selectin expression stimulated by TNF-alpha, and may imply their usefulness for the prevention of atherosclerosis relevant to endothelial activation.
Archives of Pharmacal Research 02/2005; 28(1):55-60. DOI:10.1007/BF02975136 · 2.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The petroleum ether extract of Panax ginseng showed a significant inhibition of the diacylglycerol acyltransferase (DGAT) enzyme from rat liver microsomes. Bioactivity-guided fractionation led to the isolation of two new polyacetylenic compounds, (9 R,10 S)-epoxyheptadecan-4,6-diyn-3-one ( 1) and 1-methoxy-(9 R,10 S)-epoxyheptadecan-4,6-diyn-3-one ( 2). Their chemical structures were elucidated on the basis of spectroscopic evidence and asymmetric synthesis. IC50 values of 9 microg/mL ( 1) and 32 microg/mL ( 2) were obtained.
[Show abstract][Hide abstract] ABSTRACT: Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase (DGAT). The flavonoids inhibited DGAT activity in a dose-dependent manner with IC50 values of 10.9 microM ( 1), 9.8 microM ( 2), 8.6 microM ( 3), 142.0 microM ( 4) and 250 microM ( 5). The prenylflavonoids without C3-OH ( 1, 2, 3) showed stronger inhibition than those with C3-OH ( 4, 5). On the other hand, flavonoids without side chains (hesperetin, naringenin, quercetin and kaempferol) did not inhibit the enzyme activity at a final concentration of 800 microM. These data suggest that the lavandulyl side chain and the position of the hydroxy group are important for high DGAT inhibitory activity. Compound 1 also inhibited de novo synthesis of triacylglycerol (TG) in Raji cells.
[Show abstract][Hide abstract] ABSTRACT: Cell adhesion inhibitors were isolated from the methanol extract of Saururus chinensis roots by bioactivity-guided fractionation. The active compounds were identified as manassantin A ( 1) and B ( 2), dineolignan compounds. Compounds 1 and 2 inhibited PMA-induced ICAM-1/LFA-1-mediated homotypic aggregation of the HL-60 cells without cytotoxicity with MIC values of 1.0 and 5.5 nM, respectively. Even though 1 and 2 did not affect the adhesion of ICAM-1 to LFA-1, these compounds inhibited PMA-induced ICAM-1 expression in HL-60 cells in a dose-dependent fashion. These results suggest that 1 and 2 inhibit cell aggregation through down-regulation of ICAM-1 expression.