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

• Nutrition Research and Practice
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• 제5권5호
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• pp.464-470
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• 2011

Growing evidence suggests an elevated risk for colorectal neoplasia among individuals with low levels of vitamin D, the biological actions of which are mediated by the vitamin D receptor (VDR). To investigate the association among vitamin D status, VDR polymorphisms (FokI, and BsmI), and colorectal adenoma, we conducted a meta-analysis of nine studies of circulating levels of 25-hydroxyvitamin D (25(OH)D) and five studies of FokI or BsmI polymorphisms in relation to colorectal adenomas. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. A total of 3398 coloreetal adenomas for 25(OH)D and 1754 colorectal adenomas for VDR were included in the meta-analysis. We identified a significant inverse association between colorectal adenoma (combined RR, 0.93; 95% CI, 0.87-0.98 per 10 ng/mL increase in 25(OH)D levels). When we examined FokI and BsmI polymorphisms in the meta-analysis, we found no association for either FokI (combined RR, 1.00; 95% CI, 0.95-1.06) or BsmI (combined RR, 0.99; 95% CI, 0.93-1.05) in the additive model. These data suggest an inverse association between circulating 25(OH)D levels and colorectal adenoma risk.

• Archives of Pharmacal Research
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• 제17권4호
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• pp.263-268
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• 1994

This study was conducted to characterize the in vivo pharmacology of KR-30988, KR-30992 and losartan, new AT antagonists, given as i.v. cumulative doses, in two antimal models of high renin, conscious renal artery-ligated hypertensinve rats (RHRs) and nomotensive rats anesthetized with urethane (90 mg/kg, i.p.) and .alpha.-chloralose (90 mg/kg, i.p.), with a special emphasis on the phamacological characterization of the latter model. In conscious RHRs, KR-30988, KR-30992, losartan and captopril caused a dose-dependent decrease in blood pressure, their relative potencise ($ED_{20}$) being 0.057, 0.028, 0164 and 0.018 mg/kg, i.v., repectively. In anesthetized rats, 2 hours after anesthesia, plasma renin activity was increased from 7.31 tp 34.07 ng/ml/h, the level approximately 1.5 times greater than the highest level in RHRs. In anesthtized rats, the $ED_{20}$s for all four compounds were 0.004 mg/kg i.v., respectively. By comparison, $ED_{20}$sfrom anesthetized rats were 4 to 5 times smaller than those from conscious RHRs, with a good correlation (.gamma. = 0.999) noted between thetized rats to the hypotensive activity of the compounds and the same order of potencies intwo models. These results suggest that, in addition to PHRs, the normotensive rats anesthetized as above can serve as a suitable model for the rapid phamacological evaluation of $AT_1$ receptor antagonists.

• Biomolecules & Therapeutics
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• 제14권3호
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• pp.125-131
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• 2006

The inhibitory effects of (-)-epigallocatechin gallate (EGCG), a major compound of green tea, on the development of locomotor sensitization, conditioned place preference (CPP) and dopamine receptor supersensitivity induced by the repeated administration of morphine were investigated in mice. A single administration of morphine produces hyperlocomotion. The repeated administration of morphine develops sensitization, a progressive enhancement of locomotion, which is used as a model for studying the craving and drug-seeking behaviors characterizing addiction, and CPP, which is used as a model for studying drug reinforcement, respectively. EGCG inhibited morphine-induced hyperlocomotion, sensitization and CPP. In addition, EGCG inhibited the development of postsynaptic dopamine receptors supersensitivity, which may be an underlying common mechanism that mediates the morphine-induced dopaminergic behaviors such as sensitization and CPP. Apomorphine (a dopamine agonist)-induced climbing behaviors also were inhibited by a single direct administration of EGCG These results provide evidence that EGCG has anti-dopaminergic activity, as inhibiting the development of dopamine receptor supersensitivity and apomorphine-induced climbing behaviors. Therefore, it is suggested that green tea may be useful for the prevention and therapy of these adverse actions of morphine.

• 대한약침학회지
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• 제19권2호
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• pp.163-166
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• 2016

Objectives: Quercetin is a flavonoid and an important dietary constituent of fruits and vegetables. In recent years, several pharmacological activities of quercetin, such as its neuroprotective activity and, more specifically, its anti-convulsant effects in animal models of epilepsy, have been reported. This study evaluated the role of quercetin pretreatment on gene expression of ${\gamma}$-amino butyric acid type A ($GABA_A$) receptor beta subunits in kainic acid (KA)-induced seizures in mice. Methods: The animals were divided into four groups: one saline group, one group in which seizures were induced by using KA (10 mg/kg) without quercetin pretreatment and two groups pretreated with quercetin (50 and 100 mg/kg) prior to seizures being induced by using KA. Next, the messenger ribonucleic acid (mRNA) levels of the $GABA_A$ receptor ${\beta}$ subunits in the hippocampus of each animal were assessed at 2 hours and 7 days after KA administration. Quantitative real-time polymerase chain reaction (RT-PCR) assay was used to detect mRNA content in hippocampal tissues. Results: Pretreatments with quercetin at doses of 50 and 100 mg/kg prevented significant increases in the mRNA levels of the ${\beta}_1$ and the ${\beta}_3$ subunits of the $GABA_A$ receptor at 2 hours after KA injection. Pretreatment with quercetin (100 mg/kg) significantly inhibited ${\beta}_1$ and ${\beta}_3$ gene expression in the hippocampus at 7 days after KA injection. But, this inhibitory effect of quercetin at 50 mg/kg on the mRNA levels of the ${\beta}_3$ subunit of the $GABA_A$ receptor was not observed at 7 days after KA administration. Conclusion: These results suggest that quercetin (100 mg/kg) modulates the expression of the $GABA_A$ receptor ${\beta}_1$ and ${\beta}_3$ subunits in the KA model of epilepsy, most likely to prevent compensatory responses. This may be related to the narrow therapeutic dose range for the anticonvulsant activities of quercetin.

• 대한본초학회지
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• 제22권3호
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• pp.57-65
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• 2007

Objectives : We examined to know the effect of Cordyceps sinensis(CS) on arthritis mouse induced by type II collagen. Methods : To analyse immunomodulatory effects of CS, arthritis index, incidence, hind paw edema, DTH, spleen weight, the number of hemocytes, and surface-receptor expression of CD4+, CD8+ and CD19+ cells in DBA/IJ mice which is experimental model of arthritis induced by collagen were measured in vivo. Results: CS reduced arthritis index, incidence, hind paw edema and DTH significantly as compared with the control group in experimental model of arthritis induced by collagen. CS enhanced the spleen weight significantly as compared with the control group but didn't enhanced the number of leukocytes and thrombocytes in experimental model of arthritis. CS enhanced the number of activating cells and surface-receptor expression of CD4+, CD8+ cells as compared with the control group but didn't enhanced those of CD19+ cells in experimental model of arthritis. Conclusion : We found out that CS may have a suppressing effect againist auto-immune disease and will be need continuous research in looking for the more effective mechanism in the future.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7515-7520
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• 2014

Many studies have indicated possible associations between a polymorphism of adiponectin receptor 1 (ADIPOR1) rs1342387 and risk of cancer, but contradictory results have been reported. The main aim of this study was to draw a reliable conclusion about the relationship between the rs1342387 polymorphism and cancer incidence, by conducting a literature search of Pubmed, Embase, Wanfang and Cochrane libraries. Eleven studies including 3, 738 cases and 4, 748 controls were identified in this meta-analysis. The ADIPOR1 rs1342387 polymorphism was associated with risk of colorectal cancer for all genetic comparison models (GG vs AA, OR: 1.44, 95%CI: 1.21-1.70; G carriers vs A carriers, OR: 1.23, 95%CI: 1.11-1.36; dominant model, OR: 1.28, 95%CI: 1.10-1.49 and recessive model, OR: 1.31, 95%CI: 1.12-1.55). Stratified by ethnicity, the rs1342387 polymorphism was significantly associated with risk of colorectal cancer in Asian ancestry for all genetic comparison models (GG vs AA, OR: 1.56, 95%CI: 1.26-1.92; G carriers vs. A carriers OR: 1.30, 95%CI: 1.18-1.43; dominant model OR: 1.31, 95%CI: 1.08-1.60 and recessive model OR: 1.44, 95%CI: 1.26-1.64), but not in Caucasian or mixed (Caucasian mainly) groups. In summary, the ADIPOR1 rs1342387 polymorphism is significantly associated with risk of colorectal cancer among individuals of Asian ancestry.

• 한국대기환경학회지
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• 제21권3호
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• pp.329-341
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• 2005

The purpose of this study is to study the $PM_{2.5}$ source characteristics affecting the Seoul area using a chemical mass balance (CMB) receptor model. This study was also to evaluate the $PM_{2.5}$ source profiles, which were directly measured and developed. Asian Dust Storm usually occurred in the spring, and very high $PM_{2.5}$ concentrations were observed in the fall among the sampling periods. So the ambient data collected in the spring and fall were evaluated. The CMB model results as well as the $PM_{2.5}$ source profiles were validated using the diagnostic categories, such as: source contribution estimate, t-statistic, R-square, Chi-square, and percent of total mass explained. In the spring months, the magnitude of $PM_{2.5}$ mass contributors was in the following order: Chinese aerosol $(31.7\%)>$ secondary aerosols ($22.3\%$: ammonium sulfate $13.4\%$ and ammonium nitrate $8.9\%)>$ vehicles ($16.1\%$: gasoline vehicle $1.4\%$ and diesel vehicles $14.7\%)>$biomass burning $(15.5\%)>$ geological material $(10.5\%)$. In the fall months, the general trend of the $PM_{2.5}$ mass contributors was the following: biomass burning $(31.1\%)>$ vehicles ($26.9\%$: gasoline vehicle $5.1\%$ and diesel vehicles $21.8\%)>$ secondary aerosols ($23.0\%$: ammonium sulfate $9.1\%$ and ammonium nitrate $13.9\%)>$ Chinese aerosol $(10.7\%)$. The results show that the $PM_{2.5}$ mass in the Seoul area was mainly affected by the Chinese area.

• Journal of Ginseng Research
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• 제46권4호
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• pp.526-535
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• 2022

Background: During the pathogenesis of tendinopathy, the chronic inflammation caused by the injury and apoptosis leads to the generation of scars. Ginsenoside Rg1 (Rg1) is extracted from ginseng and has anti-inflammatory effects. Rg1 is a unique phytoestrogen that can activate the estrogen response element. This research aimed to explore whether Rg1 can function in the process of tendon repair through the estrogen receptor. Methods: In this research, the effects of Rg1 were evaluated in tenocytes and in a rat model of Achilles tendinitis (AT). Protein levels were shown by western blotting. qRT-PCR was employed for evaluating mRNA levels. Cell proliferation was evaluated through EdU assay and cell migration was evaluated by transwell assay and scratch test assay. Results: Rg1 up-regulated the expression of matrix-related factors and function of tendon in AT rat model. Rg1 reduced early inflammatory response and apoptosis in the tendon tissue of AT rat model. Rg1 promoted tenocyte migration and proliferation. The effects of Rg1 on tenocytes were inhibited by ICI182780. Rg1 activates the insulin-like growth factor-I receptor (IGF1R) and MAPK signaling pathway. Conclusion: Rg1 promotes injured tendon healing in AT rat model through IGF1R and MAPK signaling pathway activation.

• 통합자연과학논문집
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• 제9권2호
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• pp.121-127
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• 2016

CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils. The neutrophilic inflammation in the lung diseases is found to be largely regulated through CXCR2 receptor. Antagonist of CXCR2 may reduce the neutrophil chemotaxis and alter the inflammatory response. Hence, in the present study, ligand based Comparative molecular field analysis (CoMFA) was performed on a series of CXCR2 antagonist named pyrimidine-5-carbonitrile-6-alkyl derivatives. The optimum CoMFA model was obtained with statistically significant cross-validated coefficients ($q^2$) of 0.568 and conventional coefficients ($r^2$) of 0.975. The contour maps suggest the important structural modifications and this study can be used to guide the development of potent CXCR2 antagonist.