• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.115-115
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• 2001

Oxidative stress induced by reactive oxygen and/or nitrogen species has been considered as a major cause of cellular injuries in a variety of neurodegenerative disorders including Alzheimers disease (AD). Inflammatory as well as oxidative tissue damage has been associated with pathophysiology of AD, and non-steroidal anti-inflammatory drugs have been reported to have beneficial effects in the treatment or prevention of AD.(omitted)

• Natural Product Sciences
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• 제16권2호
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• pp.59-67
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• 2010

Flavonoids are well-known anti-inflammatory agents that exert their effects via a variety of mechanisms including antioxidative action, inhibition of eicosanoid metabolizing enzymes and regulation of theexpression of proinflammatory molecules. In this review, synthetic approaches to obtain more useful flavonoid derivatives are summarized. Human clinical trials of flavonoid therapy are discussed. Through continual investigation to identify more potent and comparable flavonoids, new anti-inflammatory flavonoid therapy will be successfully launched, especially for the treatment of chronic inflammatory disorders.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6541-6548
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• 2013

Pigmented rice is mainly black, red, and dark purple, and contains a variety of flavones, tannin, polyphenols, sterols, tocopherols, ${\gamma}$-oryzanols, amino acids, and essential oils. The present study evaluated the cytotoxic effects of purple rice extracts (PREs) combined with chemotherapeutic drugs on human cancer cells and mechanisms of cell death. Methanolic (MeOH) and dichloromethane (DCM) extracts of three cultivars of purple rice in Thailand: Doisaket (DSK), Nan and Payao (PYO), were tested and compared with white rice (KK6). Cytotoxicity was determined by 3-(4, 5-dimethyl)-2, 5-diphenyltetrazolium bromide (MTT) assay in human hepatocellular carcinoma HepG2, prostate cancer LNCaP and murine normal fibroblast NIH3T3 cells. MeOH-PYO-PRE was the most cytotoxic and inhibited HepG2 cell growth more than that of LNCaP cells but was not toxic to NIH3T3 cells. When PREs were combined with paclitaxel or vinblastine, they showed additive cytotoxic effects on HepG2 and LNCaP cells, except for MeOH-PYO-PRE which showed synergistic effects on HepG2 cells when combined with vinblastine. MeOH-PYO-PRE plus vinblastine induced HepG2 cell apoptosis with loss of mitochondrial transmembrane potential (MTP) but no ROS production. MeOH-PYO-PRE-treated HepG2 cells underwent apoptosis via caspase-9 and-3 activation. The level of ${\gamma}$-oryzanol was highest in DCM-PYO-PRE (44.17 mg/g) whereas anthocyanin content was high in MeOH-PYO-PRE (5.80 mg/g). In conclusion, methanolic Payao purple rice extract was mostly toxic to human HepG2 cells and synergistically enhanced the cytotoxicity of vinblastine. Human HepG2 cell apoptosis induced by MeOH-PYO-PRE and vinblastine was mediated through a mitochondrial pathway.

• 대한치과교정학회지
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• 제19권1호
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• pp.61-75
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• 1989

Recently, indirect evidences suggest that Na-Ca exchange mechanism is involved in bone resorption. To study this suggestion, effects of several drugs which increase the intracellular sodium concentration by different mechanisms on the PTH-induced bone resorption were analysed employing organ culture. Ulnae and radii were removed from 19-day fetal rats, prelabelled by subcutaneous injection of $200{\mu}\;Ci^{45}CaC1_2$ on the 17th day of gestation, and then explanted on the membrane filters in organ culture dishes. For studying the effects of amiloride, ouabain, monensin, and veratridine on the PTH-induced bone resorption, control group was cultured in BGJb media containing PTH (0.4U/ml) while experimental group was cultured in BGJb media containing PTH and drugs. The effects of drugs on the PTH-induced bone resorption were observed by the ratios of $\%-release$ of $^{45}Ca$ between paired control and experimental groups. The results were as follows: 1. $^{45}Ca$ release was significantly increased by PTH (0.4U/ml) at 48 and 72 hours of culture. 2. Amiloride, at concentration of $500{\mu}M$, significantly inhibited the PTH-induced bone resorption after 48 and 72 hours of culture. 3. Ouabain, at concentration of 0.1 mM, presented significant inhibition of PTH-induced bone resorption after 48 and 72 hours of culture, and at 0.5mM and 1mM, presented significant inhibition of PTH-induced bone resorption after 72 hours of culture. 4. Monensin, at concentration of 500nM, significantly inhibited PTH-induced bone resorption after 72 hours of culture. 5. Veratridine, at concentration of 0.5mM, presented significant inhibition of PTH-induced bone resorption after 48 and 72 hours of culture, and at 1mM, presented significant inhibition of PTH-induced bone resorption after 72 hours of culture. Taken altogether, these results suggest that Na-Ca exchange mechanism play a role in PTH-induced bone resolution.

• Journal of Pharmaceutical Investigation
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• 제21권4호
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• pp.237-245
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• 1991

Matrix type silicone rubber devices were designed for long-term implantable drug delivery system. Release controlling agents (RCA), i.e., polypropylene glycol, polyethylene glycol, were employed to control drug release from the devices. The release rate of drug from RCA dispersed silicone matrices was mainly dependent on hydrophilicity-hydrophobicity of drug and RCA. In the case of hydrophilic drug, the release from the RCA dispersed matrix was regulated by swelling kinetics. Especially when the relatively hydrophobic polypropylene glycol was used, swelling control mechanism induced zero-order release kinetics. Whereas, the release of hydrophobic drug was resulted from partition mechanism. The effect of RCA was to increase drug diffusivity.

• Biomolecules & Therapeutics
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• 제26권5호
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• pp.494-502
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• 2018

Breast cancer is currently the most prevalent cancer in women, and its incidence increases every year. Azole antifungal drugs were recently found to have antitumor efficacy in several cancer types. They contain an imidazole (clotrimazole and ketoconazole) or a triazole (fluconazole and itraconazole) ring. Using human breast adenocarcinoma cells (MCF-7 and MDA-MB-231), we evaluated the effects of azole drugs on cell proliferation, apoptosis, cell cycle, migration, and invasion, and investigated the underlying mechanisms. Clotrimazole and ketoconazole inhibited the proliferation of both cell lines while fluconazole and itraconazole did not. In addition, clotrimazole and ketoconazole inhibited the motility of MDA-MB-231 cells and induced $G_1$-phase arrest in MCF-7 and MDA-MB-231 cells, as determined by cell cycle analysis and immunoblot data. Moreover, Transwell invasion and gelatin zymography assays revealed that clotrimazole and ketoconazole suppressed invasiveness through the inhibition of matrix metalloproteinase 9 in MDA-MB-231 cells, although no significant changes in invasiveness were observed in MCF-7 cells. There were no significant changes in any of the observed parameters with fluconazole or itraconazole treatment in either breast cancer cell line. Taken together, imidazole antifungal drugs showed strong antitumor activity in breast cancer cells through induction of apoptosis and $G_1$ arrest in both MCF-7 and MDA-MB-231 cells and suppression of invasiveness via matrix metalloproteinase 9 inhibition in MDA-MB-231 cells. Imidazole drugs have well-established pharmacokinetic profiles and known toxicity, which can make these generic drugs strong candidates for repositioning as antitumor therapies.

• Molecules and Cells
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• 제38권6호
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• pp.562-572
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• 2015

We previously reported the role of histone deacetylase 3 (HDAC3) in response to anti-cancer drugs. The decreased expression of HDAC3 in anti-cancer drug-resistant cancer cell line is responsible for the resistance to anti-cancer drugs. In this study, we investigated molecular mechanisms associated with regulation of HDAC3 expression. MG132, an inhibitor of proteasomal degradation, induced the expression of HDAC3 in various anti-cancer drug-resistant cancer cell lines. Ubiquitination of HDAC3 was observed in various anti-cancer drug-resistant cancer cell lines. HDAC3 showed an interaction with SIAH2, an ubiquitin E3 ligase, that has increased expression in various anti-cancer drug-resistant cancer cell lines. miRNA array analysis showed the decreased expression of miR-335 in these cells. Targetscan analysis predicted the binding of miR-335 to the 3'-UTR of SIAH2. miR-335-mediated increased sensitivity to anti-cancer drugs was associated with its effect on HDAC3 and SIAH2 expression. miR-335 exerted apoptotic effects and inhibited ubiquitination of HDAC3 in anti-cancer drug-resistant cancer cell lines. miR-335 negatively regulated the invasion, migration, and growth rate of cancer cells. The mouse xenograft model showed that miR-335 negatively regulated the tumorigenic potential of cancer cells. The down-regulation of SIAH2 conferred sensitivity to anti-cancer drugs. The results of the study indicated that the miR-335/SIAH2/HDAC3 axis regulates the response to anti-cancer drugs.

• Journal of Menopausal Medicine
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• 제24권3호
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• pp.143-149
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• 2018

Lack of adequate sleep has become increasingly common in our 24/7 modern society. Reduced sleep has significant health consequences including metabolic and cardiovascular disorders, and mental problems including depression. In addition, although the increase in life expectancy has provided a dream of longevity to humans, the occurrence of osteoporosis is a big obstacle to this dream for both male and female. It is known that insomnia and bone health problems, which are very critical conditions in human life, interestingly, share a lot of pathogenesis in recent decades. Nevertheless, due to another side effects of the synthetic drugs being taken for the treatment of insomnia and osteoporosis, patients have substantial anxiety for the safety of drugs with therapeutic expectation. This review examines the pathogenesis shared by sleep and osteoporosis together and herbal medicine, which has recently been shown to be safe and efficacious in the treatment of both diseases other than synthetic drugs. We suggestions for how to treat osteoporosis. These efforts will be the first step toward enabling patients to have comfortable and safe prescriptions through a wide selection of therapeutic agents in the future.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2169-2177
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• 2014

Matrine, a main active component extracted from dry roots of Sophora flavecens, has been reported to exert antitumor effects on A549 human non-small lung cancer cells, but its mechanisms of action remain unclear. To determine effects of matrine on proliferation of A549 cells and assess possible mechanisms, MTT assays were employed to detect cytotoxicity, along with o flow cytometric analysis of DNA content of nuclei of cells following staining with propidium iodide to analyze cell cycle distribution. Western blotting was performed to determined expression levels of Bax, Bcl-2, VEGF and HDAC1, while a microarray was used to assessed changes of miRNA profiles. In the MTT assay, matrine suppressed growth of human lung cancer cell A549 in a dose- and timedependent manner at doses of 0.25-2.5 mg/ml for 24h, 48h or 72h. Matrine induced cell cycle arrest in G0/G1 phase and decreased the G2/M phase, while down-regulating the expression of Bcl2 protein, leading to a reduction in the Bcl-2/Bax ratio. In addition, matrine down regulated the expression level of VEGF and HDAC1 of A549 cells. Microarray analysis demonstrated that matrine altered the expression level of miRNAs compared with untreated control A549 cells. In conclusion, matrine could inhibit proliferation of A549 cells, providing useful information for understanding anticancer mechanisms.

• 한국자기공명학회논문지
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• 제22권4호
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• pp.82-90
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• 2018

The term "hangover" refers to symptoms such as headache, heartburn, nausea, and dizziness caused by acetaldehyde created through alcohol decomposition in the body after alcohol intake. Many scientists have conducted research on diverse drugs, foods, and medicinal herbs aimed at eliminating hangovers. However, research on metabolism to objectively verify or measure their effects on hangover symptoms has been lacking. Accordingly, in this study, deep sea water minerals were administered orally at varying concentrations to rats that consumed alcohol, and changes in the levels of amino acids in their bodies were measured using nuclear magnetic resonance spectroscopy to gauge the minerals' effects on hangover symptoms. Thus far, biochemical research on hangover cures has been confined to basic research measuring changes in the levels of alcohol dehydrogenase and acetaldehyde dehydrogenase as well as in the concentrations of ethanol, acetaldehyde, and acetate using spectroscopes such as enzyme-linked immunosorbent assay kits or gas chromatography-mass spectrometers. In comparison, this study presents pharmacokinetic research that simultaneously tracked biomaterials including amino acids and organic acids, metabolites associated with hangover, to clarify hangover mechanisms more specifically. In addition, this study examined hangover mechanisms without an external supply of tracked materials not overlapping with alcohol metabolism-related materials, such as external amino acids and sugars.