• The Korean Journal of Physiology and Pharmacology
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• 제21권3호
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• pp.293-300
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• 2017

Prostaglandin $D_2$ ($PGD_2$) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of $PGD_2$ in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether $PGD_2$ can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. $PGD_2$ (0.1 to $10{\mu}M$) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of $PGD_2$ on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 ($1.0{\mu}M$) and AL-8810 ($1.0{\mu}M$), $PGD_2$ and prostaglandin $F2{\alpha}$ ($PGF2{\alpha}$) receptor antagonists, respectively. Moreover, $PGD_2$ clearly upregulated atrial peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and the $PGD_2$ metabolite 15-deoxy-${\Delta}12$, 14-$PGJ_2$ (15d-$PGJ_2$, $0.1{\mu}M$) dramatically increased atrial ANP secretion. Increased ANP secretions induced by $PGD_2$ and 15d-$PGJ_2$ were completely blocked by the $PPAR{\gamma}$ antagonist GW9662 ($0.1{\mu}M$). PD98059 ($10.0{\mu}M$) and LY294002 ($1.0{\mu}M$), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by $PGD_2$. These results indicated that $PGD_2$ stimulated atrial ANP secretion and promoted positive inotropy by activating $PPAR{\gamma}$ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating $PGD_2$-induced atrial ANP secretion.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.380.2-380.2
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• 2002

Peroxisome proliferator-activated receptor (PPAR)-$\gamma$ is a nuclear hormone receptor family that plays an important role in the transcriptional regulation of genes in cellular lipid and energy metabolism. In our search for Iigands for PPAR-$\gamma$ from natural resources. two phenylpropanoids. 3.4.5-Trimethoxy cinnamylalcohol (1) and 3.4.5- Trimethoxy cinnamaldehyde (2). were isolated as PPAR-$\gamma$ agonists from the MeOH extracts of Zanthoxylum schinifolium Sieb. & ZUCCo (Rutaceae) by activity-guided fractionation. These two compoundS bind and activated PPAR-$\gamma$ transcriptional activity in a dose dependent manner assessed by ligand-binding assay. While the maximum activities for PPAR-$\gamma$ of these compounds were comparable with that of rosiglitazone. which is currently used in the treatment of Type II diabetes. the potency of these compounds were much weaker than rosiglitazone ($ED_{50}$=t.2$\mu\textrm{M}$) with the $ED_{50}$ values of 9.08 and 4.08 $\mu\textrm{M}$. respectively. To examine the structure-activity relationship of phenylpropanoids. we prepared several phenylpropanoid derivatives and measured the activity. We observed that substituents at 4'- position could playa key role in determining the potency for PPAR-$\gamma$ agonistic activity .

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.180-180
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• 2003

Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, is involved in the suppression of growth of several types of tumors such as liposarcoma, cancers of breast, prostate, and colon, possibly through induction of cell cycle arrest and/or apoptosis.(omitted)

• 대한화장품학회지
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• 제35권2호
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• pp.117-123
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• 2009

후박추출물은 중국 원산인 당후박에서 제조되며, 항산화 및 항염증 효과로 알려져 있다. 후박의 성분으로는 폴레페놀인 honokiol 및 magnolol 등이 알려져 있다. 이 연구에서, 우리는 후박추출물이 triglyceride (TG)의 축척을 감소시킴으로써 지방세포 분화를 억제한다는 표면적인 결과를 얻었다. 또한, 후박 추출물이 hormone sensitive lipase (HSL) 단백질 수준을 증가시키고 adipocyte에 specific한 transcription factors로 peroxisome proliferator activated receptor (PPAR)-${\gamma}$의 단백질과 mRNA 수준을 억제하였다. 결과적으로, 후박추출물이 항비만제로서 adipogenic transcription factor와 그들의 특이적인 유전자의 발현을 억제함으로써 지방세포 분화를 억제한다고 사료된다.

• Archives of Pharmacal Research
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• 제29권5호
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• pp.394-399
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• 2006

Benzothiazole derivatives of thiazolidinediones (TZD) were synthesized using a modified Mitsunobu reaction of 2-(benzothiazol-2-ylmethylamino)ethanol (2) with 5-(4-hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione and assayed for activity on peroxisome proliferator-activated receptor (PPAR) subtypes and inhibitory activity of NO production in lipopolysaccharide-activated macrophages. Most of the tested compounds were identified as potent $PPAR_\gamma$ agonists, indicating their potential as drug candidates for diabetes.

• 대한본초학회지
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• 제20권2호
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• pp.91-102
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• 2005

Objectives : By examining the effects of Jwa Kum-Whan composed of Coptidis Rhizoma and Evodiae Fructus by the ratio of 6:1 the effects of Soo Ryeon-Whan and composed of Coptidis Rhizoma and Evodiae Fructus by the ratio of 1:1 on hyperlipidemia, the present study attempted to reveal the change of effects based on the ratio of combination. Methods : Jwa Kum-Whan and Soo Ryeon-Whan were injected to rats suffered from induced hyperlipidemia, and then its influence on lipid. During the cultivation of hepatocytes, Jwa Kum-Whan and Soo Ryeon-Whan were added to culture media, and the expression of the enzymes relevant to fat metabolism of hepatocytes was examined. Results : 1. Jwa Kum-Whan significantly decreased total cholesterol(Tc), triglyceride(TG), and LDL-cholesterol(LDLc) of rats suffering from hyperlipidemia induced by high cholesterol diet. Soo Ryeon-Whan decreased LDLc, but had no significant on Tc and TG. 2. Jwa Kum-Whan increased the expression of cholesterol esterase, LDL-receptor, diacylglycerol acyltransferase (DGAT), acylCoA-cholesterol-acyltransferase (ACAT), peroxisome proliferator activated receptor gamma $(PPAR{\gamma})$, peroxisome proliferator activated receptor alpha $(PPAR{\alpha})$ of cultivated hepatocytes. In addition, Soo Ryeon-Whan increased the expression of cholesterol esterase, LDL-Receptor, DGAT, $PPAR{\gamma},\;PPAR{\alpha}$ of cultivated hepatocytes, but had no significant effects on the expression of ACAT. Conclusion : Both Jwa Kum-Whan and Soo Ryeon-Whan were composed of Coptidis Rhizoma and Evodiae Fructus, but the fonner is more effective in hyperlipidemia.

• Radiation Oncology Journal
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• 제30권2호
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• pp.88-95
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• 2012

Purpose: The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) ${\alpha}$ and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF). Materials and Methods: Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. Results: In HeLa cells total SOD activity was increased with increasing FF doses up to 30 ${\mu}M$. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, $PPAR{\alpha}$ and $PPAR{\gamma}$ were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and $PPAR{\alpha}$ were not increased with FF. However, the mRNA of $PPAR{\gamma}$ was increased with FF. Conclusion: FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with $PPAR{\alpha}$.

• 약학회지
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• 제54권2호
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• pp.91-96
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• 2010

Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects, including anti-inflammation. It has been reported that berberine inhibits experimental colitis through inhibition of IL-8, and that inhibitory effect of berberine on inflammatory cytokine expression is mediated through peroxisome proliferator activated receptor (PPAR)-$\gamma$. In this study, we examined the effects and action mechanism of berberine on the tumor necrosis factor (TNF)-$\alpha$-induced monocyte adhesion to HT29 human colonic epithelial cells, which is commonly used as an in vitro model of inflammatory bowel disease (IBD). Berberine significantly inhibited the TNF-$\alpha$-induced monocyte adhesion to HT29, which is similar to the effect of PDTC, a nuclear factor (NF)-$\kappa$B inhibitor. However, ciglitazone and GW, the ligands of PPAR-$\gamma$, did not suppress the TNF-$\alpha$-induced monocyte adhesion to HT29 cells. In addition, TNF-$\alpha$-induced chemokine expression and NF-$\kappa$B transcriptional activity were significantly inhibited by berberine in a concentration-dependent manner. The results suggest that inhibitory effect of berberine on colitis is mediated through suppression of NF-$\kappa$B and NF-$\kappa$B-dependent chemokine expression.

• Biomolecules & Therapeutics
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• 제31권3호
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• pp.312-318
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• 2023

The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesis-inducing activity by macakurzin C derivatives (2-7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.14-40
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• 2002

15-Deoxy-${\Delta}^{12, 14}$-prostaglandin $J_2$ (15-deoxy-$PGJ_2$), a naturally occurring ligand activates the peroxisome proliferator-activated $receptor-{\gamma}(PPAR-{\gamma}$). Activation of $PPAR-{\gamma}$ has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-$PGJ_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-$PGJ_2$ (0.2 to 1.6 ${\mu}M$) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/ml). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-$PGJ_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-$PGJ_2$(0.8 ${\mu}M$) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-$PGJ_2$ on the expression of p38 MAP kinase and activation of AP-1, The promoting ability of 15-deoxy-$PGJ_2$ did not occur through $PPAR-{\gamma}$, as synthetic PPAR-${\gamma}$ agonist andantagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), $PPAR-{\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and $PGE_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of f 5-deoxy-$PGJ_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-$PGJ_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 single pathway may be important in the promoting activity of 15-deoxy-$PGJ_2$ cells.