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Archives of pharmacal research : a publication of ... 23건

  1. [국내논문]   Induction of Phase I, II and III Drug Metabolism/Transport by Xenobiotics   피인용횟수: 2

    Xu Chang Jiang (Department of Pharmaceutics, Ernest Mario School of Pharmacy ) , Li Christina YongTao (Department of Pharmaceutics, Ernest Mario School of Pharmacy ) , Kong AhNg Tony (Department of Pharmaceutics, Ernest Mario School of Pharmacy)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.3 ,pp. 249 - 268 , 2005 , 0253-6269 ,

    초록

    Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Most of the tissues and organs in our body are well equipped with diverse and various DMEs including phase I, phase II metabolizing enzymes and phase III transporters, which are present in abundance either at the basal unstimulated level, and/or are inducible at elevated level after exposure to xenobiotics. Recently, many important advances have been made in the mechanisms that regulate the expression of these drug metabolism genes. Various nuclear receptors including the aryl hydrocarbon receptor (AhR), orphan nuclear receptors, and nuclear factor-erythoroid 2 p45-related factor 2 (Nrf2) have been shown to be the key mediators of drug-induced changes in phase I, phase II metabolizing enzymes as well as phase III transporters involved in efflux mechanisms. For instance, the expression of CYP1 genes can be induced by AhR, which dimerizes with the AhR nuclear translocator (Arnt) , in response to many polycyclic aromatic hydrocarbon (PAHs). Similarly, the steroid family of orphan nuclear receptors, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), both heterodimerize with the ret-inoid X receptor (RXR), are shown to transcriptionally activate the promoters of CYP2B and CYP3A gene expression by xenobiotics such as phenobarbital-like compounds (CAR) and dexamethasone and rifampin-type of agents (PXR). The peroxisome proliferator activated receptor (PPAR), which is one of the first characterized members of the nuclear hormone receptor, also dimerizes with RXR and has been shown to be activated by lipid lowering agent fib rate-type of compounds leading to transcriptional activation of the promoters on CYP4A gene. CYP7A was recognized as the first target gene of the liver X receptor (LXR), in which the elimination of cholesterol depends on CYP7A. Farnesoid X receptor (FXR) was identified as a bile acid receptor, and its activation results in the inhibition of hepatic acid biosynthesis and increased transport of bile acids from intestinal lumen to the liver, and CYP7A is one of its target genes. The transcriptional activation by these receptors upon binding to the promoters located at the 5-flanking region of these GYP genes generally leads to the induction of their mRNA gene expression. The physiological and the pharmacological implications of common partner of RXR for CAR, PXR, PPAR, LXR and FXR receptors largely remain unknown and are under intense investigations. For the phase II DMEs, phase II gene inducers such as the phenolic compounds butylated hydroxyanisol (BHA), tert-butylhydroquinone (tBHQ), green tea polyphenol (GTP), (-)-epigallocatechin-3-gallate (EGCG) and the isothiocyanates (PEITC, sul­foraphane) generally appear to be electrophiles. They generally possess electrophilic-medi­ated stress response, resulting in the activation of bZIP transcription factors Nrf2 which dimerizes with Mafs and binds to the antioxidant/electrophile response element (ARE/EpRE) promoter, which is located in many phase II DMEs as well as many cellular defensive enzymes such as heme oxygenase-1 (HO-1), with the subsequent induction of the expression of these genes. Phase III transporters, for example, P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and organic anion transporting polypeptide 2 (OATP2) are expressed in many tissues such as the liver, intestine, kidney, and brain, and play crucial roles in drug absorption, distribution, and excretion. The orphan nuclear receptors PXR and GAR have been shown to be involved in the regulation of these transporters. Along with phase I and phase II enzyme induction, pretreatment with several kinds of inducers has been shown to alter the expression of phase III transporters, and alter the excretion of xenobiotics, which implies that phase III transporters may also be similarly regulated in a coord

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  2. [국내논문]   Open Channel Block of hKv1.5 by Psoralen from Heracleum moellendorffii Hance   피인용횟수: 4

    Eun Jae Soon (College of Pharmacy, Woosuk University ) , Cho Bok Hee (Department of Pharmacology, Chonbuk National University Medical School ) , Park Jeong Ah (Department of Pharmacology, Chonbuk National University Medical School ) , Lee Ggot Im (Department of Pharmacology, Chonbuk National University Medical School ) , Lee Taek Yul (College of Pharmacy, Woosuk University ) , Kim Dae Keun (College of Pharmacy, Woosuk University ) , Jung Young Hoon (College of Pharmacy, Woosuk University ) , Yoo Dong Jin (Department of Chemistry, Seonam University ) , Kwak Yong Geun (Department of Pharmacology, Chonbuk National University Medical School)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.3 ,pp. 269 - 273 , 2005 , 0253-6269 ,

    초록

    A furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7-one), was isolated from the n-hexane fraction of Heracleum moellendorffii Hance. We examined the effects of psor-alen on a human Kv1.5 potassium channel (hKv1.5) cloned from human heart and stably expressed in Uk- cells. We found that psoralen inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC $_{50}$ value of 180 $\pm$ 21 nM at +60 mV. Psoralen accelerated the inactivation kinetics of the hKv1.5 channel, and it slowed the deactivation kinetics of the hKv1.5 current resulting in a tail crossover phenomenon. These results indicate that psoralen acts on the hKv1.5 channel as an open channel blocker. Furthermore, psoralen prolonged the action potential duration of rat atrial muscles in a dose-dependent manner. Taken together, the present results strongly suggest that psoralen may be an ideal antiarrhythmic drug for atrial fibrillation.

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  3. [국내논문]   Inhibition of interleukin-12 production in mouse macrophagesvia decreased nuclear factor-κB DNA binding activity by myricetin, a naturally occurring flavonoid  

    Kang, Bok Yun , Kim, Seung Hyun , Cho, Daeho , Kim, Tae Sung
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.3 ,pp. 274 - 279 , 2005 , 0253-6269 ,

    초록

    A furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7-one), was isolated from the n-hexane fraction of Heracleum moellendorffii Hance. We examined the effects of psor-alen on a human Kv1.5 potassium channel (hKv1.5) cloned from human heart and stably expressed in Uk- cells. We found that psoralen inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC $_{50}$ value of 180 $\pm$ 21 nM at +60 mV. Psoralen accelerated the inactivation kinetics of the hKv1.5 channel, and it slowed the deactivation kinetics of the hKv1.5 current resulting in a tail crossover phenomenon. These results indicate that psoralen acts on the hKv1.5 channel as an open channel blocker. Furthermore, psoralen prolonged the action potential duration of rat atrial muscles in a dose-dependent manner. Taken together, the present results strongly suggest that psoralen may be an ideal antiarrhythmic drug for atrial fibrillation.

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  4. [국내논문]   Inhibition of Interleukin-12 Production in Mouse Macrophages via Decreased Nuclear $Factor-\kappaB$ DNA Binding Activity by Myricetin, a Naturally Occurring Flavonoid   피인용횟수: 2

    Kang Bok Yun (College of Pharmacy and Research Institute of Drug Development, Chonnam National University ) , Kim Seung Hyun (College of Pharmacy and Research Institute of Drug Development, Chonnam National University ) , Cho Dae Ho (Department of Life Science, Sookmyung Womens University ) , Kim Tae Sung (College of Pharmacy and Research Institute of Drug Development, Chonnam National University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.3 ,pp. 274 - 279 , 2005 , 0253-6269 ,

    초록

    Pharmacological inhibition of interleukin-12 (IL-12) production may be a therapeutic strategy for preventing the development and progression of disease in experimental models of autoimmunity. In this study, the effects of myricetin, a naturally occurring flavonoid present in fruits, vegetables and medicinal herbs, on the production of IL-12 were investigated in mouse macrophages stimulated with lipopolysaccharide (LPS). Myricetin significantly inhibited the LPS­induced IL-12 production from both primary macrophages and the RAW264.7 monocytic cell-line in a dose-dependent manner. The effect of myricetin on IL-12 gene promoter activation was analyzed by transfecting RAW264.7 cells with IL-12 gene promoter/luciferase constructs. The repressive effect was mapped to a region in the IL-12 gene promoter containing a binding site for NF- ${\kappa}B$ . Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the NF- ${\kappa}B$ site, which significantly decreased upon addition of myricetin, indicating that myricetin inhibited IL-12 production in LPS-activated macrophages via the down­regulation of NF-KB binding activity.

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    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  5. [국내논문]   Sesquiterpenes from Syneilesis palmata and Their Cytotoxicity Against Human Cancer Cell Lines In Vitro   피인용횟수: 5

    Lee Kyu Ha (Natural Products Laboratory, College of Pharmacy, Sungkyunkwan University ) , Cho Sang Un (Research Institute of Chemical Technology ) , Lee Kang Ro (Natural Products Laboratory, College of Pharmacy, Sungkyunkwan University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.3 ,pp. 280 - 284 , 2005 , 0253-6269 ,

    초록

    The chromatographic separation of the MeOH extract from the aerial parts of Syneilesis palmata led to the isolation of a new sesquiterpene glycoside 4, together with four known compounds. Their structures were characterized to be 4 $\beta$ ,5 $\beta$ -epoxy-caryophill-8,(15)-ene (1), 3 $\beta$ ­hydroxy-gultin-5-ene (2), 4 $\alpha$ ,5 $\beta$ -dihydroxy-caryophill-8,(15)-ene (3), (-)-oplopan-4-one-10- $\alpha$ -O­ $\beta$ -D-glucose (4) and 3-hexenyl-1-O- $\beta$ -D-glucopyranose (5), based on spectroscopic and chemical methods. Compound 2 showed moderate cytotoxicity against five human tumor cell lines in vitro with its EDso values ranging from 5.90-1 0.83 $\mu$ g/mL.

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  6. [국내논문]   New Cytotoxic Sulfated Saponins from the Starfish Certonardoa semiregularis  

    Wang Wei Hong (College of Pharmacy, Pusan National University ) , Jang Hyo Jin (College of Pharmacy, Pusan National University ) , Hong Jong Ki (Basic Science Institute ) , Lee Chong Ok (Korea Research Institute of Chemical Technology ) , Bae Song Ja (Silla University ) , Shin Sook (Sahmyook University ) , Jung Jee H. (College of Pharmacy, Pusan National University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.3 ,pp. 285 - 289 , 2005 , 0253-6269 ,

    초록

    Two new sulfated saponins designated as certonardosides P $_{2}$ and I $_{3}$ (1 and 2) were isolated from the brine shrimp active fraction of the MeOH extract of the starfish Certonardoa semiregularis. The structures were determined on the basis of spectral analysis. Compounds 1 and 2 were tested for cytotoxicity against five human tumor cell lines (A549, SK-OV-3, SK-MEL-2, XF498, and HCT15), and compound 1 displayed significant cytotoxicity against the SK-MEL-2 skin cancer cell.

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  7. [국내논문]   Cytotoxic Constituents of the Octocoral Dendronephthya gigantea  

    Han Ah Reum (College of Pharmacy, Ewha Womans University ) , Song Jun Im (College of Natural Science, Ewha Womens University ) , Jang Dae Sik (Department of Herbal Parmaceutical Development, Korea Institute of Oriental Medicine ) , Min Hye Young (College of Pharmacy, Ewha Womans University ) , Lee Sang Kook (College of Pharmacy, Ewha Womans University ) , Seo Eun Kyoung (College of Pharmacy, Ewha Womans University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.3 ,pp. 290 - 293 , 2005 , 0253-6269 ,

    초록

    A known monoalkyl glycerol ether, ( $\pm$ )-1-nonadecyloxy-2,3-propanediol (1) was isolated from the ethyl acetate extract of a soft coral Dendronephthya gigantea as a weakly cytotoxic constituent against four human cancer cell lines, A549, HT-29, HT-1080, and SNU-638. In addition, a known ceramide, (28,3R,4E,8E)-N-hexadecanoyl-2-amino-4,8-octadecadiene-1 ,3-diol (2), was also isolated as an inactive constituent. This is the first report on the isolation of the compounds 1 and 2 from the octocoral, Dendronephthya species.

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  8. [국내논문]   Potentially Bioactive Two New Natural Sesquiterpenoids from the Rhizomes of Zingiber zerumbet  

    Jang Dae Sik (Department of Herbal Pharmaceutical Development, Korea Institute of Oriental Medicine ) , Seol Eun Kyoung (College of Pharmacy, Ewha Womans University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.3 ,pp. 294 - 296 , 2005 , 0253-6269 ,

    초록

    Repeated chromatography of the n-hexane-soluble fraction of the MeOH extract of the rhizomes of Zingiber zerumbet led to the isolation of two isomers of 6-methoxy-2E,9E-humula-dien-8-one (1 and 2) and stigmast-4-en-3-one. The structures of 1 and 2 were determined by spectroscopic methods including 10 and 2D-NMR elucidated by analysis of spectroscopic data as well as by comparison with published values. This is the first report on the isolation of compounds 1 and 2 from the nature. Stigmast-4-en-3-one was first isolated from this plant.

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  9. [국내논문]   Flavonoids Differentially Modulate Nitric Oxide Production Pathways in Lipopolysaccharide-Activated RAW264.7 Cells   피인용횟수: 3

    Kim Ae Ra (College of Pharmacy, Pusan National University ) , Cho Jae Youl (School of Biotechnology and Bioengineering, Kangwon National University ) , Zou Yani (College of Pharmacy, Pusan National University ) , Choi Jae Sue (Faculty of Food Science and Biotechnology, Pukyong National University ) , Chung Hae Young (College of Pharmacy, Pusan National University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.3 ,pp. 297 - 304 , 2005 , 0253-6269 ,

    초록

    Naturally occurring flavonoids are known to modulate various inflammatory and immune processes. Based on structural property, in this study, molecular mechanism of flavonoids in modulating nitric oxide (NO) production and its signaling pathway were investigated using lipopolysaccharide (LPS)-activated RAW264.7 cells. Although flavonol-typed flavonoids (kaempferol and quercetin) more potently scavenged reactivity of nitric oxide ( $\cdot$ NO) as well as peroxynitrite (ONOO $\kappa$ ) than isoflavones (genistein and genistin), kaempferol, quercetin and genistein showed a little difference in inhibition of both inducible NO synthase expression and NO production, with IC $_{50}$ values of 13.9, 20.1 and 26.8 $\mu$ M. However, there was a striking pattern related to structural feature in modulation of LPS-mediated signaling pathways. Thus, flavonols only inhibited transcription factor AP-1 activation, whereas isoflavones suppressed the DNA binding activation of NF- $\kappa$ B and C/EBP $\beta$ . Therefore, these data suggest that structural feature may be linked to decide drugs target molecule in LPS-mediated signaling pathways, rather than its potency.

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    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  10. [국내논문]   Agastache rugosa leaf extract inhibits the iNOS expression in ROS 17/2.8 cells activated with TNF-α and IL-1β  

    Oh, Hwa Min , Kang, Young Jin , Kim, Sun Hee , Lee, Young Soo , Park, Min Kyu , Heo, Ja Myung , Sun, Jin ji , Kim, Hyo Jung , Kang, Eun Sil , Kim, Hye Jung , Seo, Han Geuk , Lee, Jae Heun , Yun-Choi, Hye Sook , Chang, Ki Churl
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.3 ,pp. 305 - 310 , 2005 , 0253-6269 ,

    초록

    Naturally occurring flavonoids are known to modulate various inflammatory and immune processes. Based on structural property, in this study, molecular mechanism of flavonoids in modulating nitric oxide (NO) production and its signaling pathway were investigated using lipopolysaccharide (LPS)-activated RAW264.7 cells. Although flavonol-typed flavonoids (kaempferol and quercetin) more potently scavenged reactivity of nitric oxide ( $\cdot$ NO) as well as peroxynitrite (ONOO $\kappa$ ) than isoflavones (genistein and genistin), kaempferol, quercetin and genistein showed a little difference in inhibition of both inducible NO synthase expression and NO production, with IC $_{50}$ values of 13.9, 20.1 and 26.8 $\mu$ M. However, there was a striking pattern related to structural feature in modulation of LPS-mediated signaling pathways. Thus, flavonols only inhibited transcription factor AP-1 activation, whereas isoflavones suppressed the DNA binding activation of NF- $\kappa$ B and C/EBP $\beta$ . Therefore, these data suggest that structural feature may be linked to decide drugs target molecule in LPS-mediated signaling pathways, rather than its potency.

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