• Restorative Dentistry and Endodontics
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• v.31 no.3
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• pp.203-214
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• 2006

Dental pulp is a loose, mesenchymal tissue almost entirely enclosed in the dentin. It consists of cells, ground substance, and neural and vascular supplies. Damage to the dental pulp by mechanical, chemical, thermal, and microbial irritants can provoke various types of inflammatory response. Pulpal inflammation leads to the tissue degradation, which is mediated in part by Matrix metalloproteinase leads to accelerate extracellular matrix degradation with pathological pathway We have now investigated the induction of MMPs and inflammatory cytokines by Lipopolysaccharide (LPS) control of inflammatory mediators by peroxisome proliferator-activated receptors (PPARs). Human dental pulp cells exposed to various concentrations of LPS ($1-10{\mu}g/ml$) revealed elevated levels of MMP-2 and MMP-9 at 24 hrs of culture. LPS also stimulated the production of ICAM-1, VCAM-1, $IL-1{\beta},\;and\;TNF-{\alpha}$. Adenovirus $PPAR{\gamma}\;(Ad/PPAR{\gamma})\;and\;PPAR{\gamma}$ agonist rosiglitazone reduced the synthesis of MMPs, adhesion molecules and pro-inflammatory cytokines. The inhibitory effect of $Ad/PPAR{\gamma}$ was higher than that of $PPAR{\gamma}$ agonist. These result offer new insights in regard to the anti-inflammatory potential of $PPAR{\gamma}$ in human dental pulp cell.

• Korean Journal of Plant Resources
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• v.25 no.6
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• pp.670-681
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• 2012

Herb extracts commercially used in Korea were screened for PPAR-${\gamma}$ agonist test and ${\alpha}$-glucosidase inhibition assay. Total 16 herb plants had a PPAR-${\gamma}$ agonist activity. Specially, Alisma orientale Juz (108.41%), Ephedra sinica (98.22%), Sasa japonica Makino var. purpurascens Nakai (140.68%), Astragalus membranaceus Bunge (106.79%) and Cnidium officinale Makino (113.00%) showed high PPAR-${\gamma}$ agonist activity rate compared with rosiglitazone's (167.46%). And Cornus officinalis S. et Z. (90.3%), Cinnamomum cassia Blume (89.2%), Psoralea corylifolia L. (89.8%), Paeonia japonica (Makino) Miyabe (92.4%) and Paeonia suffruticosa Andr (93.2%), showed high ${\alpha}$-glucosidase inhibition rates. These results support previous reports of the efficacy of Oriental medicinal plants used for diabetes mellitus.

• Bulletin of the Korean Chemical Society
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• v.33 no.6
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• pp.1979-1982
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• 2012

Oxime ethers of ${\beta}$-oxo-${\gamma}$-phenylbutanoic acids were prepared to develop more effective PPAR ${\alpha}$ and ${\gamma}$ dual agonists. Among them, compound 11k exhibited potent $in$ $vitro$ activities with $EC_{50}$ of 2.5 nM and 3.3 nM in PPAR ${\alpha}$ and ${\gamma}$, respectively. It showed better glucose lowering effects than rosiglitazone 1 and improved the lipid profile like plasma triglyceride in db/db mice model.

• Clinical and Experimental Pediatrics
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• v.56 no.4
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• pp.151-158
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• 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.

• Journal of Animal Science and Technology
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• v.57 no.11
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• pp.40.1-40.7
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• 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.

• Korean Journal of Food Science and Technology
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• v.38 no.1
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• pp.114-120
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• 2006

Anti-diabetic effects of extracts and fractions of Sasa borealis (SB), white lotus roots (LR) and leaves (LL), and their mixture were determined in 3T3-L1 adipocytes and Min6 cells by investigating insulin-sensitizing activity and glucose-stimulated insulin secretion, respectively. SB, LR, LL, and mixture of SB, LR, and LL (3 : 2 : 3) were extracted using 70% ethanol, and m mixture extract was fractionated by XAD-4 column chromatography with serial mixture solvents of methanol and water. Fractional extractions were utilized for anti-diabetic effect assay. SB and LR extracts increased insulin-stimulated glucose uptake, but not as much as mixture of SB, LR, and LL. Significant insulin-sensitizing activities of 20 and 80% methanol fractions of SB, LR, and LL mixture extract were observed in 3T3-L1 adipocytes, giving 0.5 or $5\;{\mu}g/mL$ each fraction with 0.2 nM insulin to attain glucose uptake level similar to that attained by 10 nM insulin alone. Similar to pioglitazone, peroxisome proliferators-activated $receptor-{\gamma}\;(PPAR-{\gamma})$ agonist, 20 and 80% methanol fractions increased adipocytes by stimulating differentiation from fibroblasts and triglyceride synthesis. LL extract and 20, 60, and 80% methanol fractions of the mixture suppressed ${\alpha}-amylase$ activity, but did not modulate insulin secretion capacity of Min6 cells in both low and high glucose media. These data suggest 20 and 80% methanol tractions contain potential insulin sensitizers with functions similar to that of $PPAR-{\gamma}$ agonist. Crude extract of SB, LR, and LL mixture possibly improves glucose utilization by enhancing insulin-stimulated glucose uptake and inhibiting carbohydrate digestion without affecting insulin secretion in vivo.

• YAKHAK HOEJI
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• v.53 no.4
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• pp.184-188
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• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.9
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• pp.1336-1343
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• 2005

In the present study, we screened candidates for enhancing insulin action and secretion from Cinnamomum camphora (CC) fractions, in 3T3-L1 adipocytes and Min6 cells by investigating insulin- stimulated glucose uptake and glucose-stimulated insulin secretion, respectively. CC were extracted by $70\%$ ethanol followed by XAD-4 column chromatography with serial mixture solvents of methanol and water, and the fractional extractions were utilized for determining insulin action and secretion, and $\alpha$-glucoamylase suppressing activity, A significant insulin-stimulated glucose uptake was observed in 3T3-L1 adipocytes, giving 0.5 or $5{\mu}g/mL$ of $40\%\;and\;60\%$ methanol fractions plus 0.2 nM insulin, compared to the treatment of DMSO plus 0.2 nM insulin. The treatments of $40\%\;and\;60\%$ methanol fractions plus 0.2 nM insulin reached the glucose uptake of 10 nM insulin treatment. The $40\%$ methanol fraction increased triglyceride accumulation by stimulating differentiation and triglyceride synthesis similar to pioglitazone, PPAR-$\gamma$ agonist. No inhibition of $\alpha$-glucoamylase activity of CC fractions was observed. They did not modulate the insulin secretion capacity In either low or high glucose media. These results suggest that $40\%$ methanol fraction contains a potential insulin sensitizer to have a similar function of PPAR-$\gamma$ agonist. Crude CC extract may improve glucose utilization by enhancing insulin-stimulated glucose uptake without elevating glucose stimulated insulin secretion.

• Journal of Life Science
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• v.20 no.7
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• pp.1113-1120
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• 2010

This study investigated the efficacy of macelignan and hot water with Chinese traditional herb (CTH) extract on altering severe diabetic conditions in C57BL/KsJ-db/db mice. Previously, the anti-diabetic effects of macelignan were partly reported as a PPAR $\alpha/\gamma$-dual agonist. Here, we futher studied whether a combination of macelignan and CTH had more beneficial effects or not. The macelignan and CTH compound significantly decreased fasting blood glucose and HbA1c compared to macelignan-treated mice, and also significantly improved postprandial glucose, insulin sensitivity, and plasma lipid profiles (FFA, and TG). On the other hand, insulin levels were not significantly changed compared to the diabetic control group. There were no significant changes in the concentrations of total cholesterol and HDL-cholesterol, but there were changes in HTR and AI. These results suggest that the macelignan and CTH compound ameliorates hyperglycemia and efficiently improves postprandial glucose, insulin sensitivity, and hyperlipidemia compared with macelignan in db/db mice. Moreover, the macelignan and CTH compound seems to be more potent in affecting diabetic complications than macelignan.

• Korean Journal of Food Science and Technology
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• v.39 no.6
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• pp.701-707
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• 2007

Anti-diabetic effect of Platycodi radix (PR) extract fractions was determined if vitro by investigating insulin-like action, insulin sensitizing action, glucose-stimulated insulin secretion, gene expression related to ${\beta}-cell$ function and mass, and ${\alpha}$-glucoamylase suppressing action. Insulin-like activity was not promoted by the treatment of PR methanol factions in 373-L1 fibroblast. However, treatment with 0, 20 and 100% PR methanol fractions along with 1 ng/mL insulin increased insulin-stimulated glucose uptake in 373-L1 adipocytes. In addition, the treatment of 0% and 100% methanol fractions along with differentiation inducers significantly increased the differentiation of 373-L1 fibroblasts to adipocytes. These fractions may contain insulin sensitizer. The 20%, 80% and 100% methanol fractions enhanced glucose-stimulated insulin secretion in Min6 cells, insulin secreting cell line. This was related to the mechanism to promote glucose sensing and ${\beta}-cell$ proliferation, which was regulated by the induction of IRS-2, glucokinase and PDX-1 genes. As expected, 20, 80 and 100% methanol fractions increased mRNA levels of IRS-2, glucokinase and PDX-1 genes. However, PR fractions did not affect the ${\alpha}-glucoamylase$ activity in vitro. These data suggested that PR extract fractions have anti-diabetic actions through improving insulin sensitization, glucose-stimulated insulin secretion, and ${\beta}-cell$ proliferation. Therefore, PR extracts can be beneficial for anti-diabetic treatment in lean diabetic patients.