• YAKHAK HOEJI
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• v.54 no.2
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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.

• Radiation Oncology Journal
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• v.30 no.2
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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 $PPAR{\alpha}$.

• Bulletin of the Korean Chemical Society
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• v.32 no.1
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• pp.201-207
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• 2011

Peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors and their activation induces regulation of fatty acid storage and glucose metabolism. Therefore, the $PPAR\gamma$ is a major target for the treatment of type 2 diabetes mellitus. In order to generate pharmacophore model, 1080 known agonists database was constructed and a training set was selected. The Hypo7, selected from 10 hypotheses, contains four features: three hydrogen-bond acceptors (HBA) and one general hydrophobic (HY). This pharmacophore model was validated by using 862 test set compounds with a correlation coefficient of 0.903 between actual and estimated activity. Secondly, CatScramble method was used to verify the model. Hence, the validated Hypo7 was utilized for searching new lead compounds over 238,819 and 54,620 chemical structures in NCI and Maybridge database, respectively. Then the leads were selected by screening based on the pharmacophore model, predictive activity, and Lipinski's rules. Candidates were obtained and subsequently the binding affinities to $PPAR\gamma$ were investigated by the molecular docking simulations. Finally the best two compounds were presented and would be useful to treat type 2 diabetes.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.207.3-208
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• 2003

Peroxisome proliferator-activated receptor (PPAR), a member of the nuclear hormone receptor superfamily, is a transcription factor activated by specific natural or synthetic ligands. It is involved in various cellular processes including adipogenesis, inflammation, cell cycle progression and carcinogenesis. Here, we report the production and characterization of a PPARgamma subtype-specific monoclonal antibody P${\gamma}$ 48.34A, which was raised against full-length human PPARgamma protein. (omitted)

• Journal of Microbiology and Biotechnology
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• v.25 no.3
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• pp.334-342
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• 2015

4-O-Methylhonokiol (MH), a bioactive compound derived from Magnolia officinalis, is known to exhibit antitumor effects in various cancer cells. However, the precise mechanism of its anticancer activity in cervical cancer cells has not yet been studied. In this study, we demonstrated that MH induces apoptosis in SiHa cervical cancer cells by enhancing peroxisome proliferator-activated receptor-gamma (PPARγ) activation, followed by inhibition of the PI3K/Akt pathway and intrinsic pathway induction. MH upregulated PPARγ and PTEN expression levels while it decreased p-Akt in the MH-induced apoptotic process, thereby supporting the fact that MH is a PPARγ activator. Additionally, MH decreased the expression of Bcl-2 and Bcl-XL, inducing the intrinsic pathway in MH-treated SiHa cells. Furthermore, MH treatment led to the activation of caspase-3/caspase-9 and proteolytic cleavage of polyADP ribose polymerase. The expression levels of Fas (CD95) and E6/E7 oncogenes were not altered by MH treatment. Taken together, MH activates PPARγ/PTEN expression and induces apoptosis via suppression of the PI3K/Akt pathway and mitochondria-dependent pathways in SiHa cells. These findings suggest that MH has potential for development as a therapeutic agent for human cervical cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.321-331
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• 2021

Vancomycin, an antibiotic used occasionally as a last line of treatment for methicillin-resistant Staphylococcus aureus, is reportedly associated with nephrotoxicity. This study aimed at evaluating the protective effects of lutein against vancomycin-induced acute renal injury. Peroxisome proliferator-activated receptor gamma (PPARγ) and its associated role in renoprotection by lutein was also examined. Male BALB/c mice were divided into six treatment groups: control with normal saline, lutein (200 mg/kg), vancomycin (250 mg/kg), vancomycin (500 mg/kg), vancomycin (250 mg/kg) with lutein, and vancomycin (500 mg/kg) with lutein groups; they were euthanized after 7 days of treatment. Thereafter, samples of blood, urine, and kidney tissue of the mice were analyzed, followed by the determination of levels of N-acetyl-β-D-glucosaminidase (NAG) in the urine, renal creatine kinase; protein carbonyl, malondialdehyde, and caspase-3 in the kidney; and the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappaB (NF-κB) in renal tissue. Results showed that the levels of protein carbonyl and malondialdehyde, and the activity of NAG, creatine kinase and caspase-3, were significantly increased in the vancomycin-treatment groups. Moreover, the levels of Nrf2 significantly decreased, while NF-κB expression increased. Lutein ameliorated these effects, and significantly increased PPARγ expression. Furthermore, it attenuated vancomycin-induced histological alterations such as, tissue necrosis and hypertrophy. Therefore, we conclude that lutein protects against vancomycin-induced renal injury by potentially upregulating PPARγ/Nrf2 expression in the renal tissues, and consequently downregulating the pathways: inflammation by NF-κB and apoptosis by caspase-3.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.149.2-150
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• 2002

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.150.1-150.1
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• 2002

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.495-495
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• 2021

• Molecules and Cells
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• v.44 no.1
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• pp.1-12
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• 2021

The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is the master transcriptional regulator in adipogenesis. PPARγ forms a heterodimer with another nuclear receptor, retinoid X receptor (RXR), to form an active transcriptional complex, and their transcriptional activity is tightly regulated by the association with either coactivators or corepressors. In this study, we identified T-cell death-associated gene 51 (TDAG51) as a novel corepressor of PPARγ-mediated transcriptional regulation. We showed that TDAG51 expression is abundantly maintained in the early stage of adipogenic differentiation. Forced expression of TDAG51 inhibited adipocyte differentiation in 3T3-L1 cells. We found that TDAG51 physically interacts with PPARγ in a ligand-independent manner. In deletion mutant analyses, large portions of the TDAG51 domains, including the pleckstrin homology-like, glutamine repeat and proline-glutamine repeat domains but not the proline-histidine repeat domain, are involved in the interaction with the region between residues 140 and 506, including the DNA binding domain, hinge, ligand binding domain and activation function-2 domain, in PPARγ. The heterodimer formation of PPARγ-RXRα was competitively inhibited in a ligand-independent manner by TDAG51 binding to PPARγ. Thus, our data suggest that TDAG51, which could determine adipogenic cell fate, acts as a novel negative regulator of PPARγ by blocking RXRα recruitment to the PPARγ-RXRα heterodimer complex in adipogenesis.