• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.1
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• pp.15-21
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• 2018

Skin-aging is accelerated by the increased expression of MMP-1 caused by the increased skin temperature induced by IR/visible light as well as UV. Thus, the control of skin temperature is important to inhibit heat-induced aging. Many studies have been conducted to lower the skin temperature through the controlling transient receptor potential melastatin 8 channel (TRPM8), which is known as the cold and menthol receptor 1 (CMR1) and is activated at temperature below $25^{\circ}C$. In this study, we first investigated the effect of Ganoderma lucidum extract (GLE) on the TRPM8 expression. Results showed that GLE, hexane (Hex) fractions and water fractions increased the TRPM8 expression in a dose dependent manner. Active compound in Hex fractions were separated by chromatography and analyzed by $^1H$ and $^{13}C$ NMR spectroscopy. The isolated compounds were identified as ergosterol and it also significantly increased the TRPM8 expression. Taken together, these results strongly suggest that G. lucidum extract and ergosterol have the potential as a new cooling ingredient in the cosmetics.

• Journal of Integrative Natural Science
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• v.5 no.1
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• pp.32-37
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• 2012

Chemokine receptor antagonists have potential applications in field of drug discovery. Although the chemokine receptors are G-protein-coupled receptors, their cognate ligands are small proteins (8 to 12 kDa), and so inhibiting the ligand/receptor interaction has been challenging. The application of structure-based in-silico methods to drug discovery is still considered a major challenge, especially when the x-ray structure of the target protein is unknown. Such is the case with human CCR2 and CCR5, the most important members of the chemokine receptor family and also a potential drug target. Herein, we review the success stories of combined receptor modeling/mutagenesis approach to probe the allosteric nature of chemokine receptor binding by small molecule antagonists for CCR2 and CCR5 using Rhodopsin as template. We also urged the importance of recently available ${\beta}2$-andrenergic receptor as an alternate template to guide mutagenesis. The results demonstrate the usefulness and robustness of in-silico 3D models. These models could also be useful for the design of novel and potent CCR2 and CCR5 antagonists using structure based drug design.

• Bulletin of the Korean Chemical Society
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• v.31 no.12
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• pp.3760-3764
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• 2010

We screened 10,000 heterocyclic small molecules and identified a novel hit core skeleton of 3-(8-chloro-6-(trifluoromethyl) imidazo[1,2-a]pyridine-2-yl)phenyl acetate derivatives. It has been selected as a potential glucagon-like peptide 1 receptor (GLP-1R) activator and demonstrated its effects in increasing GLP-1 secretion, and thereby increasing the glucose responsiveness in both in vitro and pharmacology analyses. Further studies are currently underway to optimize the potency and selectivity of 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl acetate derivatives (hit compounds 2 and 8), and address their in vivo efficacy and therapeutic potential. These molecules may serve as useful evidence showing that compounds with a 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl acetate moiety are selective GLP-1R agonists, and have potential as anti-diabetic treatment agents.

• Archives of Pharmacal Research
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• v.28 no.4
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• pp.405-412
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• 2005

A vanilloid receptor (VR1, now known as TRPV1) is an ion channel activated by vanilloids, including capsaicin (CAP) and resiniferatoxin (RTX), which are pungent ingredients of plants. Putative endogenous activators (anandamide and metabolites of arachidonic acid) are weak activators of VR1 compared to capsaicin and RTX, and the concentrations of the physiological condition of those activators are not sufficient to induce significant activation of VR1. One way to overcome the weak activation of endogenous activators would be the sensitization of VR1, with the phosphorylation of the channel being one possibility. The phosphorylation of VR1 by several kinases has been reported, mostly by indirect evidence. Here, using an in vivo phosphorylation method, the VR1 channel was shown to be sensitized by phosphorylation of the channel itself by multiple pathways involving PKA, PKC and acid. Also, in sensitizing VR1, BK appeared to show activation of PKC for the sensitization of VR1 by phosphorylation of the channel.

• Molecules and Cells
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• v.44 no.12
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• pp.900-910
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• 2021

Sour is one of the fundamental taste modalities that enable taste perception in animals. Chemoreceptors embedded in taste organs are pivotal to discriminate between different chemicals to ensure survival. Animals generally prefer slightly acidic food and avoid highly acidic alternatives. We recently proposed that all acids are aversive at high concentrations, a response that is mediated by low pH as well as specific anions in Drosophila melanogaster. Particularly, some carboxylic acids such as glycolic acid, citric acid, and lactic acid are highly attractive to Drosophila compared with acetic acid. The present study determined that attractive carboxylic acids were mediated by broadly expressed Ir25a and Ir76b, as demonstrated by a candidate mutant library screen. The mutant deficits were completely recovered via wild-type cDNA expression in sweet-sensing gustatory receptor neurons. Furthermore, sweet gustatory receptors such as Gr5a, Gr61a, and Gr64a-f modulate attractive responses. These genetic defects were confirmed using binary food choice assays as well as electrophysiology in the labellum. Taken together, our findings demonstrate that at least two different kinds of receptors are required to discriminate attractive carboxylic acids from other acids.

• Fisheries and Aquatic Sciences
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• v.18 no.2
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• pp.211-220
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• 2015

We investigated the differences in the expression of the neurohormones kisspeptin (Kiss) and gonadotropin-inhibitory hormone (GnIH) and cytochrome P450 aromatase (P450arom), gonadotropin hormones (GTHs), and sex steroids in the goldfish Carassius auratus exposed to light-emitting diodes (LEDs). The expression levels of Kiss1, Kiss2, G-protein-coupled receptor 54 (GPR54), GTHs, GnIH, and P450arom were compared between the control (white light) and LED-treated goldfish. Furthermore, we measured the plasma levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The levels of Kiss1 mRNA and protein; Kiss2, GPR54, and $GTH{\alpha}$ protein; GTH mRNA; and plasma FSH and LH in the hypothalamus and cultured hypothalamus cells were significantly higher in the green and purple LED treatment groups than in the other groups. These results suggested that red LEDs inhibit the sex maturation hormones, Kiss, GPR54, GTHs, and P450arom, and that GnIH plays a role in the negative regulation of reproductive function in goldfish.

• Toxicological Research
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• v.29 no.3
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• pp.217-219
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• 2013

Hypertension is a serious health problem due to high frequency and concomitant other diseases including cardiovascular and renal dysfunction. Olmesartan cilexetil is a new antihypertensive drug associated with angiotensin II receptor antagonist. This study was conducted to evaluate the mutagenicity of olmesartan cilexetil by bacterial reverse mutation test using Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) and Escherichia coli (WP2 uvrA). At the concentrations of 0, 62, 185, 556, 1667, and 5000 ${\mu}g$/plate, olmesartan cilexetil was negative in both Salmonella typhimurium and Escherichia coli regardless of presence or absence of metabolic activation system (S9 mix). These results demonstrate that olmesartan cilexetil does not induce bacterial reverse mutation.

• Molecules and Cells
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• v.39 no.4
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• pp.310-315
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• 2016

Coumarin is a phenolic compound that mainly affects the liver due to its metabolization into a toxic compound. The deterrent and ovicidal activities of coumarin in insect models such as Drosophila melanogaster have been reported. Here we explore the molecular mechanisms by which these insects protect themselves and their eggs from this toxic plant metabolite. Coumarin was fatal to the flies in a dosage-dependent manner. However, coumarin feeding could be inhibited through activation of the aversive gustatory receptor neurons (GRNs), but not the olfactory receptor neurons. Furthermore, three gustatory receptors, GR33a, GR66a, and GR93a, functioned together in coumarin detection by the proboscis. However, GR33a, but not GR66a and GR93a, was required to avoid coumarin during oviposition, with a choice of the same substrates provided as in binary food choice assay. Taken together, these findings suggest that anti-feeding activity and oviposition to avoid coumarin occur via separate mechanisms.

• Bulletin of the Korean Chemical Society
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• v.27 no.9
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• pp.1285-1286
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• 2006

• Bulletin of the Korean Chemical Society
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• v.29 no.8
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• pp.1479-1484
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• 2008

Protein tyrosine phosphatase (PTP) 1B is the superfamily of PTPs and a negative regulator of multiple receptor tyrosine kinases (RTKs). Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a strategy for the treatment of type 2 diabetes and obesity. Recently, it has been reported that amentoflavone, a biflavonoid extracted from Selaginella tamariscina, inhibited PTP1B. In the present study, docking model between amentoflavone and PTP1B was determined using automated docking study. Based on this docking model and the interactions between the known inhibitors and PTP1B, we determined multiple pharmacophore maps which consisted of five features, two hydrogen bonding acceptors, two hydrogen bonding donors, and one lipophilic. Using receptor-oriented pharmacophore-based in silico screening, we searched the biflavonoid database including 40 naturally occurring biflavonoids. From these results, it can be proposed that two biflavonoids, sumaflavone and tetrahydroamentoflavone can be potent allosteric inhibitors, and the linkage at 5',8''-position of two flavones and a hydroxyl group at 4'-position are the critical factors for their allosteric inhibition. This study will be helpful to understand the mechanism of allosteric inhibition of PTP1B by biflavonoids and give insights to develop potent inhibitors of PTP1B.