• Bulletin of the Korean Chemical Society
• /
• 제32권8호
• /
• pp.2717-2721
• /
• 2011

Peroxisome proliferator-activated receptors (PPARs) are a subfamily of nuclear receptors (NRs). Human peroxisome proliferator-activated receptor gamma (hPPAR${\gamma}$) has been implicated in the pathology of numerous diseases, including obesity, diabetes, and cancer. ELISA-based hPPAR${\gamma}$ activation assay showed that biapigenin increased the binding between hPPAR${\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 3-fold. In order to confirm that biapigenin binds to hPPAR${\gamma}$, fluorescence quenching experiment was performed. The results showed that biapigenin has higher binding affinity to hPPAR${\gamma}$ at nanomolar concentrations compared to indomethacin. Biapigenin showed anticancer activity against HeLa cells. Biapigenin was noncytotoxic against HaCa T cell. All these data implied that biapigenin may be a potent agonist of hPPAR${\gamma}$ with anticancer activity. We will further investigate its anticancer effects against human cervical cancer.

• Bulletin of the Korean Chemical Society
• /
• 제33권5호
• /
• pp.1475-1479
• /
• 2012

Human peroxisome proliferator-activated receptor gamma ($hPPAR{\gamma}$) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. In this study, we verified that amentoflavone is an agonist of $hPPAR{\gamma}$ and probed the molecular basis of its action. It was demonstrated that amentoflavone bound $hPPAR{\gamma}$ with high (picomolar) affinity and increased the binding between $hPPAR{\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 4-fold. Based on a docking study, for the first time, we propose a model of amentoflavone and $hPPAR{\gamma}$ binding in which amentoflavone forms three hydrogen bonds with the side chains of His323, Tyr327, and Arg280 in $hPPAR{\gamma}$ and participates in two hydrophobic interactions.

• Clinical and Experimental Reproductive Medicine
• /
• 제40권2호
• /
• pp.67-75
• /
• 2013

Objective: To investigate the effect of peroxisome proliferator activated receptor ${\gamma}$(PPAR${\gamma}$) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis. Methods: Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPAR${\gamma}$ agonist). Results: We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPAR${\gamma}$ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin $E_2$ production in the ESCs of endometriosis. Conclusion: This study suggests that PPAR${\gamma}$ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.

• Journal of Animal Science and Technology
• /
• 제57권11호
• /
• pp.40.1-40.7
• /
• 2015

Background: Activation of peroxisome proliferator activated receptor gamma ($PPAR{\gamma}$) in the alveolar macrophages (AM) by selective synthetic $PPAR{\gamma}$ ligands, improves the ability of the cells to resolve inflammation. In birds, respiratory macrophages are known as free avian respiratory macrophages (FARM) and show distinct functional differences from AM. The effects of treating FARM with $PPAR{\gamma}$ ligands are unclear. Methods: FARM were harvested by lavage of chicken respiratory tract and their morphology assessed at microscopic level. The effects of $PPAR{\gamma}$ agonists on the FARM in vitro viability, phagocytic capacity and proinflammatory cytokine (TNF-${\alpha}$) production were assessed. Results: FARM had eccentric nucleus and plasma membrane ruffled with filopodial extensions. Ultrastructurally, numerous vesicular bodies presumed to be lysosomes were present. FARM treated with troglitazone, a selective $PPAR{\gamma}$ agonist, had similar in vitro viability with untreated FARM. However, treated FARM co-cultured with polystyrene particles, internalized more particles with a mean volume density of 41 % compared to that of untreated FARM of 21 %. Further, treated FARM significantly decreased LPS-induced TNF-${\alpha}$ production in a dose dependent manner. Conclusion: Results from this study show that $PPAR{\gamma}$ synthetic ligands enhance phagocytic ability of FARM. Further the ligands attenuate production of proinflammatory cytokines in the FARM, suggesting potential therapeutic application of $PPAR{\gamma}$ ligands in the management of respiratory inflammatory disorders in the poultry industry.

• Biomolecules & Therapeutics
• /
• 제18권1호
• /
• pp.77-82
• /
• 2010

Peroxisome proliferator-activated receptor $\gamma$ (PPAR${\gamma}$) is a ligand-activated transcription factor that is used as a target for anti-diabetic drug development. In a search for novel PPAR${\gamma}$ agonists, the $\beta$-carboxyethyl-rhodanine derivative SP1818 was identified. We report here the characteristics of SP1818 as a selective PPAR${\gamma}$ agonist. In transactivation assays, SP1818 selectively activated PPAR${\gamma}$, but the degree of PPAR${\gamma}$ stimulation was less than with $1{\mu}M$ rosiglitazone. SP1818 also stimulated glucose uptake in a concentration-dependent manner. The adipocyte differentiation markers adiponectin, scavenger receptor CD36 and aP2 were weakly induced by treatment with SP1818, and TRAP220 subunit was specifically recruited into PPAR${\gamma}$ activated by rosiglitazone but not PPAR${\gamma}$ activated by SP1818.

• Food Science and Biotechnology
• /
• 제17권6호
• /
• pp.1146-1150
• /
• 2008

Peroxisome proliferator-activated receptor-gamma ($PPAR_{\gamma}$), a member of the nuclear receptor of ligand-activated transcription factors, plays a key role in lipid and glucose metabolism or adipocytes differentiation. A lignan compound was isolated from mace (the aril of Myristica fragrans Houtt.) as a $PPAR_{\gamma}$ ligand, which was identified as fragrin A or 2-(4-allyl-2,6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)-propane. To ascertain whether fragrin A has $PPAR_{\gamma}$ ligand-binding activity, it was performed that GAL-4/$PPAR_{\gamma}$ transactivation assay. $PPAR_{\gamma}$ ligand-binding activity of fragrin A increased 4.7, 6.6, and 7.3-fold at 3, 5, and $10{\mu}M$, respectively, when compared with a vehicle control. Fragrin A also enhanced adipocytes differentiation and increased the expression of $PPAR_{\gamma}$ target genes such as adipocytes fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and phosphoenol pyruvate carboxykinase (PEPCK). Furthermore, it significantly increased the expression level of glucose transporter 4 (GLUT4). These results indicate that fragrin A can be developed as a $PPAR_{\gamma}$ agonist for the improvement of insulin resistance associated with type 2 diabetes.

• The Korean Journal of Physiology and Pharmacology
• /
• 제10권4호
• /
• pp.181-186
• /
• 2006

This study was undertaken to evaluate whether peroxisome proliferator-activated-receptor-gamma $(PPAR-{\gamma})$ agonist-rosiglitazone (ROSI) induces postischemic functional recovery in Langendorf heart model. Hearts isolated from normal rats were subjected to 20 min of normoxia or 25 min zero-flow ischemia followed by 50 min reperfusion. In this acute protocol, ROSI $(20\;{\mu}g/ml)$ administered 10 min before ischemia had no effect on hemodynamic cardiac function, but had protective effect on lipid peroxidation in in vitro experiments. In chronic protocol in which ROSI was given by daily gavage (4 mg/kg) for three consecutive days, ROSI could not prevent the hemodynamic alteration on cardiac performance, but has protective effect on the activity of superoxide dismutase (SOD). There was no significant difference in the contents of reduced glutathione (GSH) and catalase activity between ischemia-reperfusion (IR) and ROSI treated IR hearts. Although ROSI had no effect on hemodynamic factor, it had effect on antioxidant activity. Our results indicate that ROSI provides partial beneficial effects by inhibiting lipid peroxidation and/or recovering normal level of SOD activity in the ischemic reperfused heart.

• Clinical and Experimental Pediatrics
• /
• 제56권4호
• /
• pp.151-158
• /
• 2013

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$, PPAR-${\gamma}$, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-${\gamma}$ agonist. Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-${\alpha}$, transforming growth factor (TGF)-${\beta}$, PPAR-${\alpha}$ and PPAR-${\gamma}$ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPAR${\alpha}$ and PPAR-${\gamma}$ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-${\alpha}$, and TGF-${\beta}$ mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-${\beta}$ expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. Conclusion: PPAR-${\alpha}$ and PPAR-${\gamma}$ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• 제23권4호
• /
• pp.346-355
• /
• 2020

Purpose: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. Methods: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. Results: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-β1) was also downregulated in the BDL+TZD group (p=0.0087). Conclusion: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-β1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

• 약학회지
• /
• 제53권4호
• /
• pp.184-188
• /
• 2009

Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs in the treatment of advanced colorectal cancer patients. Capsaicin (N-vanillyl-8-methyl-alpha-nonenamide), a spicy component of hot pepper, is a homovanillic acid derivative that preferentially induces cancer cells to undergo apoptosis. The purpose of the present study is to examine whether capsaicin enhances the anticancer effect of 5-fluorouracil in HT-29 human colon cancer cells by inducing apoptosis, and whether PPARgamma is involved in the capsaicin action in combination treatment with 5-FU. Treatment of the cells with either 5-FU or capsaicin alone for 48 h had little effect on the cell viability up to $50{\mu}M$ concentration, whereas co-treatment of the cells with capsaicin in the presence of 5-FU for 48 h significantly decreased the cell viability in a concentration-dependent manner. In addition, caspase-3 activity, a marker enzyme for apoptosis, was significantly increased by the combined treatment with 5-FU and capsaicin compared to the 5-FU or capsaicin alone treatment. Also, treatment with troglitazone, a peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) agonist, further enhanced the effect of the combination treatment on the cell viability and caspase-3 activity, and bisphenol A diglycidyl ether (BADGE), a $PPAR{\gamma}$ antagonist, blocked the effect of the combination treatment. These results suggest that the combination treatment of HT-29 cells with 5-FU and capsaicin induces apoptotic cell death at relatively low concentration than each drug alone, and the combination treatment may be associated with the $PPAR{\gamma}$ pathway activation.