• Korean Journal of Food Science and Technology
• /
• v.35 no.3
• /
• pp.503-509
• /
• 2003

For the development of the anti-obesity natural drug, the inhibitor of adipocyte differentiation was screened from Korean traditional medicinal plants. Phellodendri Cortex was selected as a candidate of adipocyte differentiation inhibitor. An inhibitory compound PC-4 was purified from the methanol (MeOH) extract of Phellodendri Cortex using silica gel and ODS RP-18 column chromatography and HPLC. PC-4 was obtained as yellow powder; UV ${\lambda}_{max}$ (MeOH): 230, 260, 340 and 430 nm. The chemical structure of PC-4 was determined as an isoquionoline alkaloid, berberine, on the basis of various NMR experiments including $^1H-\;and\;^{13}C-NMR$. The PC-4 inhibited the differentiation of preadipocyte NIH-3T3 L1 cells at a concentration of $1\;{\mu}g/mL$.

• Biomolecules & Therapeutics
• /
• v.17 no.4
• /
• pp.348-352
• /
• 2009

Over the last decade, the incidence of overweight and obesity has nearly doubled in many countries and is considered a pandemic. Obesity was identified as a major risk factor for cardiovascular disease as the same level as smoking and diabetes. Visceral fat is considered one of the key contributors to outcome and certain ethnic groups such as Asians seem to be more affected than others. Weight reduction through lifestyle changes was found to be impactful to improve overall health, but weight loss and maintenance thereof is limited and difficult to sustain. Surgical intervention demonstrated a greater weight loss in the severely obese and was associated with improved all-cause mortality. Despite numerous pharmacological targets and a high medical need, only few drugs have been successfully developed. Earlier studies with amphetamine-derived compounds showed significant weight loss but their critical safety profiles led to market withdrawals and disappointment. More recent compounds; orlistat - a lipase inhibitor, rimonabant - a cannaboid-1-receptor antagonist, and sibutramine - a combined serotonin/norepinephrine re-uptake inhibitor, all demonstrated similar significant efficacy; however, they carry specific safety profiles making them unsuitable for every patient. The main limitation of pharmacotherapy is the absence of clear benefit-risk assessments through outcome studies. Such a study - the SCOUT trial - was designed to compare sibutramine versus placebo and the effect on morbidity and mortality in nearly 10,000 obese patients with additional risk factors. Such studies could provide new scientific evidence for obesity treatment and may support future pharmacological approaches.

• Journal of Nutrition and Health
• /
• v.48 no.1
• /
• pp.9-18
• /
• 2015

Purpose: Poncirus trifoliata has been reported to have anti-inflammatory, antioxidant, and immune activities. However, its anti-obesity activity and the mechanism by which the water extract of dried, immature fruit of Poncirus trifoliata (PF-W) acts are not clear. This study suggests a potential mechanism associated with the anti-obesity activity of PF-W. Methods: We measured the effect of PF-W on lipoprotein lipase (LPL) regulation using enzyme-linked immunosorbent assay (ELISA) and an activity assay. The LPL regulation mechanism was examined by reverse transcription polymerase chain reaction (RT-PCR) to measure the mRNA expression of biomarkers related to protein transport and by western blot for analysis of the protein expression of the transcription factor CCAAT-enhancer-binding protein ($C/EBP{\beta}$). Results: The total polyphenol and flavonoid content of PF-W was $52.15{\pm}4.02$ and $6.56{\pm}0.47mg/g$, respectively. PF-W treatment decreased LPL content in media to $58{\pm}5%$ of that in control adipocyte media, and increased LPL content to $117{\pm}3.5%$ of that in control adipocytes, but did not affect the mRNA expression of LPL. PF-W also increased the mRNA expression of sortilin-related receptor (SorLA), a receptor that induces endocytosis and intracellular trafficking of LPL, in a concentration- and time-dependent manner. Finally, cell fractionation revealed that PF-W treatment induced the expression of $C/EBP{\beta}$, a SorLA transcription factor, in the nuclei of 3T3-L1 adipocytes. Conclusion: The LPL secretion and activity assay showed PF-W to be an LPL secretion inhibitor, and these results suggest the potential mechanism of PF-W involving inhibition of LPL secretion through $C/EBP{\beta}$-mediated induction of SorLA expression.

• Korean journal of food and cookery science
• /
• v.18 no.3
• /
• pp.319-324
• /
• 2002

In a previous study, we developed a new food additive as an egg yolk antibody (IgY) against carbohydrate digestion enzymer for the regulation of blood glucose level and weight control. The IgY delayed and decreased the increment if blood glucose level after administration of sucrose in human being by 30% in 20∼30 min. We also developed a lipase inhibitor as a water extract of two kinds of herb, Platycodon grandiflorum and Solanum Melongena, Twenty three volunteers were subjected to the intake of the egg yolk IgY Plus the herbal extracts for 50 days. In average, the treated subjects appeared to lose 1.96 kg of body weight and 3.4 kg of body fat mass during the treated period. Furthermore, Panniculus adiposus and breech size were significantly decreased during the experimental period. Above results suggested that the administration of the dietary additives composed of egg yolk IgY and natural herbal extract improve the obesity by the decrement of body weight and body fat mass.

• Journal of the Korean Chemical Society
• /
• v.48 no.2
• /
• pp.161-170
• /
• 2004

A series of ${\gamma}$-aminobutyric acid-derived, potent human cytosolic phospholipase A$_2$ inhibitors have been prepared from acyl cyanophosphoranes and amine derivatives in a convergent manner. The ${\alpha}$-keto amide functionalities in the inhibitors have been introduced as electrophilic fragments via direct coupling reactions between the labile ${\alpha},{\beta}$-diketo nitriles and ${\gamma}$-aminobutyric acid t-butyl ester derivatives at -78 $^{\circ}C$ in moderate to good yields.

• Journal of Chest Surgery
• /
• v.42 no.2
• /
• pp.263-267
• /
• 2009

A pancreatico-pleural fistula (PPF), caused by rupture of a pancreatic pseudocyststectomy or obstruction of the pancreatic duct, is a rare condition. A 48-year-old man with chronic alcoholism was admitted with a massive pleural effusion. Pleural fluid studies revealed elevated amylase and lipase. A PPF complicated by a ruptured pancreatic pseudocyststectomy was diagnosed by computerized tomography scan. Although the symptoms improved with conservative management, (chest tube drainage, NPO, total parenteral nutrition, and a pancreatic secretion inhibitor), a distal pancreatectomy, including a pseudocystectomy and thoracotomy, were performed for an increasing size of the hemorrhagic pancreatic pseudocyststectomy and a recurrent hemorrhagic pleural effusion. There were no post-operative complications and the patient was discharged on post-operative day 27.

• Biomedical Science Letters
• /
• v.14 no.3
• /
• pp.131-137
• /
• 2008

Adipogenesis is a complex sequence of events that culminates in the differentiation of fibroblast-like preadipocytes into specialized lipid-filled adipocytes and also involves a cascade of expression of many transcription factors such as peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$ and CCAAT/enhancer-binding proteins (C/EBPs). $PPAR{\gamma}$ and C/EBPs transcriptionally transactivate adipocyte specific genes, including fatty acid transport protein (FAT/CD36) and leptin. To determine whether $17{\beta}$-estradiol modulates $C/EBP{\alpha}$ actions on adipogenesis in high fat diet-fed female ovariectomized (OVX) C57BL/6 mice, mice were treated with $17{\beta}$-estradiol for 7 days and the effects of $17{\beta}$-estradiol on adipose tissue mass and expression of adipocyte specific gene as well as $C/EBP{\alpha}$ were measured. Compared to vehicle-treated OVX control mice, OVX mice treated with $17{\beta}$-estradiol for 7 days had lower adipose tissue weights that were similar to weights in high fat diet-fed sham-operated (Sham) mice. OVX mice showed the increased expression of $C/EBP{\alpha}$ mRNA compared with Sham mice. However, $17{\beta}$-estradiol treatment in OVX mice inhibited OVX induced-$C/EBP{\alpha}$ activation, indicating that $17{\beta}$-estradiol may act as an inhibitor of $C/EBP{\alpha}$ action. Moreover, $17{\beta}$-estradiol decreased mRNA levels of adipocyte marker genes, such as lipoprotein lipase, FAT/CD36 and leptin, to levels in Sham mice. These results suggest that down-regulation of adipogenesis by $17{\beta}$-estradiol may be due to reduced adipose $C/EBP{\alpha}$ activities in female OVX C57BL/6 mice.

• Journal of Life Science
• /
• v.13 no.6
• /
• pp.924-932
• /
• 2003

Epigallocatechin-3 Gallate (EGCG), a major constituent of green tea, has attracted increasing interest because of its many reported health benefits. Here we demonstrate for the first time that EGCG stimulates phospholipase D (PLD) activity in U87 human astroglioma cells. EGCG-induced PLD activation was abolished by the phospholipase C (PLC) inhibitor and a lipase inactive PLC-\gama1$ mutant, and was dependent on intracellular $Ca^{ 2+}$, and possibly involved $Ca^{ 2+}$ calmodulin-dependent protein kinase II (CaM kinase II). Interestingly, EGCG induced translocation of PLC-\gama1$ from the cytosol to the membrane and PLC-\gama1$interaction with PLD1. Taken together, these results demonstrate for the first time that in human astroglioma cells, EGCG regulates PLD activity via a signaling pathway involving a PLC-\gama1$ (inositol 1,4,5-trisphosphate-$Ca^{ 2+}$)-CaM kinase II-PLD pathway.

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.4
• /
• pp.299-307
• /
• 2015

Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis.

• Biomolecules & Therapeutics
• /
• v.27 no.6
• /
• pp.591-602
• /
• 2019

Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231. Although G0S2 acts as a direct inhibitor of adipose triglyceride lipase, action of G0S2 in cancer progression is not yet understood. To investigate whether G0S2 affects invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin-regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. In addition, G0S2 downregulation decreased ${\beta}$-catenin expression, while E-cadherin expression was increased. It was demonstrated for the first time that G0S2 mediates the Hippo pathway and induces epithelial to mesenchymal transition (EMT). Taken together, our results suggest that G0S2 is a major factor contributing to cell survival and metastasis of MDA-MB-231 cells.