Woojung Lee

Sargaquinoic acid and sargahydroquinoic acid from Sargassum yezoense stimulate adipocyte differentiation through PPARα/γ activation in 3T3-L1 cells

We screened active compounds from natural marine products able to increase PPARα/γ transcriptional activity. Sargaquinoic acid (SQA) and sargahydroquinoic acid (SHQA) from Sargassum yezoense were identified as novel PPARα/γ dual agonists. The binding affinity of SQA with PPARγ was higher than that of the specific PPARγ agonist troglitazone, leading to an activation of PPARγ transcriptional activity. In parallel, treatment of 3T3‐L1 cells with SQA and SHQA led to an increase in adipocyte differentiation and increased expression of adipogenic marker genes such as aP2, PPARγ, resistin, adiponectin, C/EBPα and Glut4. Collectively, our data suggest that SQA and SHQA are novel PPARα/γ dual agonists and may be beneficial for reducing insulin resistance through regulation of adipogenesis.

Photoautotrophic hydrogen production by eukaryotic microalgae under aerobic conditions

Eukaryotic algae and cyanobacteria produce hydrogen under anaerobic and limited aerobic conditions. Here we show that novel microalgal strains (Chlorella vulgaris YSL01 and YSL16) upregulate the expression of the hydrogenase gene (HYDA) and simultaneously produce hydrogen through photosynthesis, using CO2 as the sole source of carbon under aerobic conditions with continuous illumination. We employ dissolved oxygen regimes that represent natural aquatic conditions for microalgae. The experimental expression of HYDA and the specific activity of hydrogenase demonstrate that C. vulgaris YSL01 and YSL16 enzymatically produce hydrogen, even under atmospheric conditions, which was previously considered infeasible. Photoautotrophic H2 production has important implications for assessing ecological and algae-based photolysis.

Inhibitory effect of chalcones and their derivatives from Glycyrrhiza inflata on protein tyrosine phosphatase 1B

Compounds (1-6) isolated from the CH(2)Cl(2) extract of Glycyrrhiza inflata and semisynthetic licochalcone A derivatives (7-14) were evaluated for their protein tyrosine phosphatase 1B (PTP1B) inhibitory activities. Licochalcones A (4) and E (6), each with an allyl group at position 5 in the B ring exhibited significant inhibitory effects. Licochalcone A derivative 7, the most potent among the series, had an IC(50) value of 11.7+/-2.0 microM, ca. twofold better than that of licochalcone A (4).

Histone Deacetylase Inhibitor Induction of P-Glycoprotein Transcription Requires Both Histone Deacetylase 1 Dissociation and Recruitment of CAAT/Enhancer Binding Protein β and pCAF to the Promoter Region

Although histone deacetylase (HDAC) inhibitors are appreciated as a promising class of anticancer drugs, recent reports show that P-glycoprotein (P-gp) is induced by HDAC inhibitor treatment in cancer cells, resulting in multidrug resistance of cancer cells to other chemotherapeutic agents. In this study, we investigated the molecular mechanism of HDAC inhibitor induction of P-gp expression. HDAC inhibitor treatment causes cell type–specific induction of P-gp expression without changes in the CpG methylation status of the promoter region. In addition, our data show that HDAC inhibitor does not alter the DNA binding activity of Sp1 but facilitates both the recruitment of a coactivator complex that includes CAAT/enhancer binding protein β and pCAF and the dissociation of the repressive complex, HDAC1, to the Sp1 binding region. Subsequently, the hyperacetylated histone H3 becomes enriched in the promoter region, leading to RNA polymerase II recruitment to activate P-gp gene transcription. Furthermore, specific down-regulation of HDAC1, but not HDAC2, by RNA silencing was enough to induce P-gp expression in HeLa cells, strongly supporting the essential role of HDAC1 in HDAC inhibitor induction of P-gp. Concomitantly, cell type–specific induction of P-gp expression seems to be dependent on phosphatidylinositol 3-kinase activity. Taken together, our findings show that HDAC inhibitor treatment leads to an increase in P-gp expression through dynamic changes in chromatin structure and transcription factor association within the promoter region. (Mol Cancer Res 2009;7(5):735–44)

Dendrobium moniliforme Attenuates High-Fat Diet-Induced Renal Damage in Mice through the Regulation of Lipid-Induced Oxidative Stress

Obesity is an important and preventable risk factor for renal disease. The administration of an antioxidant with a lipid-lowering effect is an important therapeutic approach for kidney disease in obese patients. The present study was conducted to examine whether methanolic extract of Dendrobium moniliforme (DM), one of the most famous traditional medicines used in many parts of the world, has an antioxidant effect in vitro and an ameliorative effect on high-fat diet (HFD)-induced alterations such as renal dysfunction and lipid accumulation in vivo. The 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of DM extract (IC(50) = 29.6 μg/mL) was increased in a dose-dependent manner. The LLC-PK1 kidney cell damage induced by oxidative stress was significantly inhibited by the treatments with DM extract. In the animal study, DM extract (200 mg/kg) was orally administered every day for nine weeks to HFD-fed mice, and its effect was compared with that of metformin. The administration of DM extract decreased the elevated serum glucose, total cholesterol concentration and renal lipid accumulation in HFD-fed mice. It also ameliorated renal dysfunction biomarkers including serum creatinine and renal collagen IV deposition. Taken together, these results provide important evidence that DM extract exhibits a pleiotropic effect on obesity induced parameters and exerted a renoprotective effect in HFD-fed mice.

Design, synthesis, and evaluation of bromo-retrochalcone derivatives as protein tyrosine phosphatase 1B inhibitors.

A series of bromo-retrochalcones was designed, synthesized and evaluated as PTP1B inhibitors based on licochalcone A and E. Compounds 6, 12, 13, 14, 25, 36, 37, 39, and 41 showed potent inhibitory effects against PTP1B, and compound 37, the most potent among the series, had an IC(50) value of 1.9 μM, about two-fold better than that of the positive control, ursolic acid.

Chemical and Free Radical-scavenging Activity Changes of Ginsenoside Re by Maillard Reaction and Its Possible Use as a Renoprotective Agent

Reactive oxygen species play critical role in kidney damage. Free radical-scavenging activities of Panax ginseng are known to be increased by heat-processing. The structural change of ginsenoside and the generation of Maillard reaction products (MRPs) are closely related to the increased free radical-scavenging activities. In the present study, we have demonstrated the Maillard reaction model experiment using ginsenoside Re and glycine mixture to identify the renoprotective effect of MRPs from ginseng or ginsenosides. Ginsenoside Re was transformed into less-polar ginsenosides, namely Rg2, Rg6 and F4 by heat-processing. The free radical-scavenging activity of ginsenoside Re-glycine mixture was increased in a temperature-dependant manner by heatprocessing. The improved free radical-scavenging activity by heat-processing was mediated by the generation of antioxidant MRPs which led to the protection of LLC-PK1 renal epithelial cells from oxidative stress. Although the free radical scavenging activities of less-polar ginsenosides were weak, they could protect LLC-PK1 cells from oxidative stress. Therefore, MRPs and less-polar ginsenosides contributed to the combined renoprotective effects against oxidative renal damage.

Anti-obesity and hypolipidemic effects of Rheum undulatum in high-fat diet-fed C57BL/6 mice through protein tyrosine phosphatase 1B inhibition

Protein tyrosine phosphatase 1B (PTP1B) is important in the regulation of metabolic diseases and has emerged as a promising signaling target. Previously, we reported the PTP1B inhibitory activity of Rheum undulatum (RU). In the present study, we investigated the metabolic regulatory effects of RU in a high-fat diet (HFD) model. RU treatment significantly blocked body weight gain, which was accompanied by a reduction of feed efficiency. In addition, it led to a reduction of liver weight mediated by overexpression of PPARα and CPT1 in the liver, and an increase in the expression of adiponectin, aP2, and UCP3 in adipose tissue responsible for the reduction of total and LDL-cholesterol levels. Chrysophanol and physcion from RU significantly inhibited PTP1B activity and strongly enhanced insulin sensitivity. Altogether, our findings strongly suggest that 2 compounds are novel PTP1B inhibitors and might be considered as anti-obesity agents that are effective for suppressing body weight gain and improving lipid homeostasis.

Increase in antioxidant effect of ginsenoside Re-alanine mixture by Maillard reaction.

Ginsenoside Re, one of the major triol type ginsenosides contained in Panax ginseng, has a hydrophobic four-ring steroid-like structure with hydrophilic sugar moieties at carbon-3 and -20. The aim of the present study was to identify the changes in structure and antioxidant activity of ginsenoside Re by the Maillard reaction, which has not been reported yet. The free radical-scavenging activity of ginsenoside Re-alanine mixture was increased by heat-processing. Ginsenoside Re was gradually changed into Rg(2), Rg(6) and F(4) by heat-processing, and the glucosyl moiety at carbon-20 was separated. The improved-free radical-scavenging activity by heat-processing was mediated by the generation of antioxidant Maillard reaction products (MRPs). Antioxidant MRPs were generated from the reaction of glucose and alanine. Based on the viability results of LLC-PK1 renal epithelial cells, MRPs and less-polar ginsenosides contributed to the combined renoprotective effect against oxidative renal damage. Maillard reaction is importantly involved in the increased antioxidant effect of ginsenoside by heat-processing.

Protective effect of esculin on streptozotocin-induced diabetic renal damage in mice.

The present study investigated the presence and mechanism of esculin-mediated renoprotection to assess its therapeutic potential. Esculin was orally administered at 20 mg/kg/day for 2 weeks to streptozotocin-induced diabetic mice, and its effects were compared with those of the vehicle in normal and diabetic mice. After oral administration of esculin to mice, the concentrations of esculin and esculetin in blood were 159.5 ± 29.8 and 9.7 ± 4.9 ng/mL at 30 min, respectively. Food and water intake were significantly increased in the diabetic mice compared to normal mice but attenuated in mice receiving esculin. The elevated blood glucose level and hepatic glucose-6-phosphatase expression were significantly reduced in esculin-treated diabetic mice, supporting the antidiabetic effect of esculin. Esculin also increased the uptake of glucose and induced the insulin-evoked phosphorylation of insulin receptor, Akt, and glycogen synthase kinase 3β in C2C12 myotubes, indicating a potential for improvement of insulin sensitivity. In addition, esculin lessened the elevated blood creatinine levels in diabetic mice and ameliorated diabetes-induced renal dysfunction by reducing caspase-3 activation in the kidney. Data support the beneficial effect of esculin against diabetes and oxidative stress-related inflammatory processes in the kidney.