• 제목/요약/키워드: Systems pharmacology

검색결과 282건 처리시간 0.035초

신약개발과 안전성약리시험 가이드라인 (Drug Development and Guideline for Safety Pharmacology Studies)

  • 최기환;박인숙;임화경;오우용;왕소영;김소희;김주일;김동섭
    • 약학회지
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    • 제47권2호
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    • pp.104-109
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    • 2003
  • The present paper reviews the notion and comparison of the Korea Food and Drug Administration(KFDA) general pharmacology and the International Conference on Harmonisation (ICH) safety pharmacology. General pharmacology or safety pharmacology is termed the study to determine the potential of a compound to induce adverse pharmacological effects. KFDA general pharmacology studies have been considered an important component in drug safety assessment and these were originally referred to those designed to examine effects other than the primary therapeutics effect of a drug candidate. The KFDA notified the Guideline for General Pharmacology in 1997. Safety pharmacology studies were focused on identifying adverse effects on physiological functions. In the ICH came into place S7A Safety Pharmacology Studies for Human Pharmaceuticals in 2001. A new chemical entity should be assessed for its side effects, initially in those physiological systems which are generally agreed to be the key systems that are essential for life; these "core system" include the central nervous system, cardiovascular system and respiratory system in safety pharmacology studies. These studies should be performed in compliance with Good Laboratory Practice (GLP).

Systems Biology - A Pivotal Research Methodology for Understanding the Mechanisms of Traditional Medicine

  • Lee, Soojin
    • 대한약침학회지
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    • 제18권3호
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    • pp.11-18
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    • 2015
  • Objectives: Systems biology is a novel subject in the field of life science that aims at a systems' level understanding of biological systems. Because of the significant progress in high-throughput technologies and molecular biology, systems biology occupies an important place in research during the post-genome era. Methods: The characteristics of systems biology and its applicability to traditional medicine research have been discussed from three points of view: data and databases, network analysis and inference, and modeling and systems prediction. Results: The existing databases are mostly associated with medicinal herbs and their activities, but new databases reflecting clinical situations and platforms to extract, visualize and analyze data easily need to be constructed. Network pharmacology is a key element of systems biology, so addressing the multi-component, multi-target aspect of pharmacology is important. Studies of network pharmacology highlight the drug target network and network target. Mathematical modeling and simulation are just in their infancy, but mathematical modeling of dynamic biological processes is a central aspect of systems biology. Computational simulations allow structured systems and their functional properties to be understood and the effects of herbal medicines in clinical situations to be predicted. Conclusion: Systems biology based on a holistic approach is a pivotal research methodology for understanding the mechanisms of traditional medicine. If systems biology is to be incorporated into traditional medicine, computational technologies and holistic insights need to be integrated.

Systems pharmacology approaches in herbal medicine research: a brief review

  • Lee, Myunggyo;Shin, Hyejin;Park, Musun;Kim, Aeyung;Cha, Seongwon;Lee, Haeseung
    • BMB Reports
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    • 제55권9호
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    • pp.417-428
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    • 2022
  • Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which impedes the development and application of herbal medicine. To address this, recent studies are increasingly adopting systems pharmacology, which interprets pharmacological effects of drugs from consequences of the interaction networks that drugs might have. Most conventional network-based approaches collect associations of herb-compound, compound-target, and target-disease from individual databases, respectively, and construct an integrated network of herb-compound-target-disease to study the complex mechanisms underlying herbal treatment. More recently, rapid advances in high-throughput omics technology have led numerous studies to exploring gene expression profiles induced by herbal treatments to elicit information on direct associations between herbs and genes at the genome-wide scale. In this review, we summarize key databases and computational methods utilized in systems pharmacology for studying herbal medicine. We also highlight recent studies that identify modes of action or novel indications of herbal medicine by harnessing drug-induced transcriptome data.

Pharmacology of enantiomers of higenamine and related tetrahydroisoquinolines

  • Park, Min-Kyu;Huh, Ja-Myung;Lee, Young-Soo;Kang, Young-Jin;Seo, Han-Geuk;Lee, Jae-Heun;Park, Hye-Sook-Yun-;Lee, Duck-Hyung;Chang, Ki-Churl
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2004년도 Annual Meeting of KSAP : New Drug Development from Natural Products
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    • pp.3-10
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    • 2004
  • Oxidative stress is a constant threat to all living organisms and an immense repertoire of cellular defense systems is being employed by most pro- and eukaryotic systems to eliminate or to attenuate oxidative stress. Ischemia and reperfusion is characterized by both a significant oxidative stress and characteristic changes in the antioxidant defense. Heme oxigenase-l (HO-l) is up-regulated by various stimuli including oxidative stress so that it is thought to participate in general cellular defense mechanisms against ischemic injury in mammalian cells. Higenamine, an active ingredient of Aconite tuber, has been shown to have antioxidant activity along with inhibitory action of inducible nitric oxide synthase (iNOS) expression in various cells. In the present study, we investigated whether higenamine and related analogs protect cells from oxidative cellular injuries by modulating antioxidant enzymes, such as HO-l, MnSOD etc. R-form of YS-51 was the most potent inducer of HO-l in bovine endothelial cells, which inhibited apoptotic cell death by H$_2$O$_2$. HO-1 induction by YS 51 was mediated by PI3 kinase activation in which PKA- as well as PKG pathway is considered as important regulators. YS-51 also induced Mn-SOD mRNA expression by activating c-jun N-terminal kinase in endothelial cells and Hela cells. In ROS 17/2.1 cells, higenamine and enetiomers of related compounds inhibited iNOS expression by cytokine mixtures. Taken together, higenamine and related compounds can be developed as possible protective agents from oxidative cell injury or death.

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METHAMPHETAMINE-INDUCED CYTOTOXICITY IN HUMAN SEROTONERGIC CELLS

  • Kim, Kyu-Bong;Suh, Soo-Kyung;Lee, Bo-Kyung;Park, Chang-Won;Seo, Kyung-Won;Kim, Jong-Won;Kim, Kwang-Jin;Kim, Jae-Hee;Park, Chan-Woong
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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    • pp.190-190
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    • 2002
  • Methamphetamine (META) is a psychostimulant and has become popular recreational drug of abuse in many countries. The neurotoxic damage caused by METH is characterized by degeneration of the dopaminergic and serotonergic systems in striatum and hippocampus.(omitted)

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인삼사포닌의 전처치 부위에 따른 Morphine 진통력 길항작용 (Antagonism of Morphine Analgesia by the Pretreatment Sites with Ginseng Total Saponin)

  • Kim, Hack-Seang;Oh, Ki-Wan;Oh, Sei-Kwan;Ryu, Hang-Mook;Seong, Yeon-Hee
    • Journal of Ginseng Research
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    • 제15권1호
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    • pp.6-12
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    • 1991
  • The analgesic effect of morphine was antagonized in mice pretreated with ginseng total saponin intraperitoneally, intracerebrally and intrathecally. The antagonized effects of morphine analgesia were reversed predominantly by treatment with L-3, 4-dihydroxyphenylalanine in the tail pinch test and 5-hydroxytryptophan in the tail flick test respectively. These indicate that the antagonistic action of ginseng total saponin might be due to their inhibitions of the activation of descending ihibitory systems at the cerebral site as well as spinal. In addition, any appreciable changes of brain biogenic monoamine levels were not observed in mice pretreated with ginseng total saponin at various time intervals. These results obtained suggest that a newly equilibrated state of neurologic function could be found in mice pretreated with ginseng total saponin, and modification of neurologic function in the mechanism for the antagonism of morphine analgesia by ginseng total saponin was more important than the changes of brain biogenic monoamine levels.

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Influence of the Central Benzodiazepinergic System on Peripheral Cardiovascular Regulation

  • Koh, Jeong-Tae;Ju, Jeong-Min;Shin, Dong-Ho;Cho, Han-Ho;Choi, Bong-Kyu;Kim, Jae-Ha
    • The Korean Journal of Physiology and Pharmacology
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    • 제2권3호
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    • pp.287-295
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    • 1998
  • Diazepam is known to have cardiovascular depressive effects through a combined action on benzodiazepinergic receptor and the GABA receptor-chloride ion channel complex. Moreover, it is known that barbiturates also have some cardiovascular regulatory effects mediated by the central GABAergic system. Therefore, this study was undertaken to delineate the regulatory actions and interactions of these systems by measuring the responses of the cardiovascular system and renal nerve activity to muscimol, diazepam and pentobarbital, administered intracerebroventricularly in rabbits. When muscimol $(0.03{\sim}0.3\;{\mu}\;g/kg)$, diazepam $(10{\sim}100\;{\mu}\;g/kg)$ and pentobarbital $(1{\sim}10\;{\mu}\;g/kg)$ were injected into the lateral ventricle of the rabbit brain, there were similar dose-dependent decreases in blood pressure (BP) and renal nerve activity (RNA). The relative potency of the three drugs in decreasing BP and RNA was muscimol > pentobarbital > diazepam. Muscimol and pentobarbital also decreased the heart rate in a dose-dependent manner; however, diazepam produced a trivial, dose-independent decrease in heart rate. Diazepam $(30\;{\mu}g/kg)$ augmented the effect of muscimol $(0.1\;{\mu}g/kg)$ in decreasing blood pressure and renal nerve activity, but pentobarbital $(3\;{\mu}g/kg)$ did not. Bicuculline $(0.5\;{\mu}g/kg)$, a GABAergic receptor blocker, significantly attenuated the effect of muscimol in decreasing BP and RNA, either alone or with diazepam, and that of pentobarbital in decreasing BP and RNA, either alone or with muscimol. We inferred that the central benzodiazepinergic and barbiturate systems help regulate peripheral cardiovascular function by modulating the GABAergic system, which adjusts the output of the vasomotor center and hence controls peripheral sympathetic tone. Benzodiazepines more readily modulate the GABAergic system than barbiturates.

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Assay development and HTS on microfluidic Lab-on-a-chip

  • Yang, Eun-Gyeong
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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    • pp.73-78
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    • 2002
  • Microfluidic lab-on-a-chip (LOC) systems have enabled a new generation ofassay technologies in chemical and biomedical sciences. Caliper's microfluidic LOC systems contain a network of microscopic channels through which fluids and chemical are moved in order to perform experiments. The main advantages of these continuous-flow devices are integration and automation of multiple steps in complex analytical procedures to improve the reproducibility of the results, and eliminated the manual labor, time and pipetting errors involved in analyses. The present talk is devoted to give a brief introduction of microfluidic basics and to present in applying continuous-flow microchips to drug screening with model enzyme assays.

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죽염의 일반약리작용 (General Pharmacology of Bamboo Salt)

  • 유태무;김순선;노용남;이숙영;김옥희;류항묵;양지선
    • Biomolecules & Therapeutics
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    • 제8권1호
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    • pp.93-98
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    • 2000
  • This study has been carried out to investigate general pharmacological action of bamboo salt (jukyom) in terms of effects on central nervous system and cardiovascular system in experimental animals. After bamboo salt, crude salt or reagent-grade NaCl were orally administered into male ICR mice with dose of 2.0 g/kg, general behavioural syndromes such as body weight and locomotor activity, spontaneous motor activity, pento-barbital-induced sleeping time, muscle incoordination, electroshock-induced convulsion, body temperature and writhing response caused by 0.6% acetic acid solution were observed. Bamboo salt had no influences in these indices for examinition of effect on central nervous system. Additionally, conscious male Sprague Dawley rats fastened overnight won ere treated with bamboo salt, crude salt or reagent-grade NaCl (2.0 g/kg, p.o.) to examine the effect of these salts cardiovascular system. Systolic, median and diastolic food pressure and heart rate were dertemined using tail cuff indirect method. Treatment with Hydralazine (50 mg/kg, p.o) as a positive control produced the decreases in systolic, median and diastolic blood treasure and an increase in heart rate. whereas no changes were observed in bamboo salt, crude salt and reagent-grade NaCl treated groups. These results strongly suggest that bamboo salt may have no effects on general pharmacology of central nervous systems and cardio-vascular systems.

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