• Title/Summary/Keyword: mechanisms of action

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Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach

  • Park, Sa-Yoon;Park, Ji-Hun;Kim, Hyo-Su;Lee, Choong-Yeol;Lee, Hae-Jeung;Kang, Ki Sung;Kim, Chang-Eop
    • Journal of Ginseng Research
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    • v.42 no.1
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    • pp.98-106
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    • 2018
  • Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng, it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng, a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

Molecular Mechanisms of Casticin Action: an Update on its Antitumor Functions

  • Rasul, Azhar;Zhao, Bin-Ji;Liu, Jun;Liu, Bao;Sun, Jia-Xin;Li, Jiang;Li, Xiao-Meng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9049-9058
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    • 2014
  • Casticin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone) is an active compound isolated from roots, stems, leaves, fruits and seeds of a variety of plants. It is well known for its pharmacological properties and has been utilized as an anti-hyperprolactinemia, anti-tumor, anti-inflammatory, neuroprotetective, analgesic and immunomodulatory agent. Recently, the anticancer activity of casticin has been extensively investigated. The resulkts showed that it exerts protective potential by targeting apoptosis, considered important for cancer therapies. In this article, our aim was to review the pharmacological and therapeutic applications of casticin with specific emphasis on its anticancer functions and related molecular mechanisms. Chemotherapeutic effects are dependent on multiple molecular pathways, which may provide a new perspective of casticin as a candidate anti-neoplastic drug. This review suggests that additional studies and preclinical trials are required to determine specific intracellular sites of action and derivative targets in order to fully understand the mechanisms of its antitumor activity and validate this compound as a medicinal agent for the prevention and treatment of various cancers.

Intracellular Mechanisms of Growth Hormone Action on Apoptosis in Cultured Porcine Ovarian Granulosa Cells

  • Sirotkin, A.V.;Makarevich, A.V.;Pivko, J.;Genieser, H.G.
    • Asian-Australasian Journal of Animal Sciences
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    • v.15 no.7
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    • pp.1045-1050
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    • 2002
  • The aims of this study were to detect spontaneously occurring apoptosis in cultured porcine ovarian cells, to examine the role of growth hormone (GH), tyrosine kinase (TK), protein kinase G (PKG) and cyclin-dependent kinase (CDK) in the control of this process, and to determine whether the effect of GH on apoptosis is mediated by TK-, PKG- and cdc2-dependent intracellular mechanisms. We studied the action of pGH (10 ng/ml), blockers of TK (genistein, lavendustin, both 100 ng/ml), PKG (Rp-Br-PET-cGMPS, 50 nM; KT5823, 100 ng/ml) and CDK (olomoucine, $1{\mu}g/ml$), as well as combinations of GH with these blockers, on the onset of apoptosis in cultured granulosa cells isolated from antral (3-6 mm) porcine follicles. The functional characteristics of an early apoptotic event, DNA fragmentation, were determined using terminal deoxynucleotidyltransferase (TdT)-mediated dUTP nick end labelling (TUNEL), whilst morphological signs of advanced apoptosis such as pyknosis, chromatin marginalization, shrinkage and fragmentation of nucleus, were detected using routine light microscopy. After culture, some ovarian granulosa cells exhibited DNA fragmentation, which in some cases was associated with morphological apoptosis-related changes (pyknosis, shrinkage and fragmentation of the nucleus). GH significantly reduced the proportion of TUNEL-positive cells. Neither TK nor CDK blockers when given alone, significantly affected the percentage of TUNEL-positive cells although both PKG blockers significantly increased this index. Furthermore, TK and PKG blockers given together with GH, prevented or reversed the inhibitory effect of GH on apoptosis, whilst the CDK blocker olomoucine promoted it. These observations demonstrate apoptosis in porcine ovaries and suggest the involvement of GH, TK, PKG and CDK in the control of this process. They also suggest that the effect of GH on ovarian apoptosis is mediated or regulated by multiple signalling pathways including TK-, PKG- and CDK-dependent intracellular mechanisms.

Collapse-resistant performance of a single-story frame assembly and multi-story sub-frame under an internal column-removal scenario

  • Zhong, Wei-hui;Tan, Zheng;Tian, Li-min;Meng, Bao;Zheng, Yu-hui;Daun, Shi-chao
    • Steel and Composite Structures
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    • v.41 no.5
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    • pp.663-679
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    • 2021
  • To elucidate the differences in the collapse behavior between a single-story beam-column assembly and multi-story frame, two 1/3-scale two-bay composite frames, including a single-story composite beam-column assembly and a three-story composite sub-frame, were designed and quasi-statically tested. The load-displacement responses, failure modes, and internal force development of the two frames were analyzed and compared in detail. Furthermore, the resistance mechanisms of the two specimens were explored, and the respective contributions of different load-resisting mechanisms to the total resistances were quantitatively separated to gain deeper insights. The experimental tests indicated that Vierendeel action was present in the two-dimensional multi-story frames, which led to an uneven internal force distribution among the three stories. The collapse resistance of TSDWA-3S in the flexural stage was not significantly increased by the structural redundancy provided by the additional story, as compared to that of TSDWA-1S. Although the development of the load response was similar in the two specimens at flexural stage, the collapse mechanisms of the multi-story composite frame were much more complicated than those of the single-story beam-column assembly, and the combined action between stories was critical in determining the internal force redistribution and rebalancing of the remaining structure.

Light Therapy : Basic Principle and Clinical Practice (광치료의 기본원리와 임상 실제)

  • Joe, Sook-Haeng
    • Sleep Medicine and Psychophysiology
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    • v.5 no.2
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    • pp.170-176
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    • 1998
  • Nowadays light therapy is accepted practice in the treatment for Seasonal Affective Disorder. The author reviewed the practical aspects of light therapy, latest treatment research on optimal parameters of light therapy and the mechanisms of action of light therapy. Therapeutic efficacy of light therapy using light visors & dawn simulators has been suggested but further studies are needed to clarify the efficacy. The treatment most strongly supported by research studies is light therapy using a light box to administer bright white light (2500 lux for 2 hours or 10000 lux for 30 minutes). Although some patients may be selective responders to morning light exposure, the optimal timing of light exposure still remains controversial. In practice, generally the duration of exposure can be increased or decreased as necessary and also the timing of exposure can be splitted (e.g. AM/PM usage) if optimal response is obtained. For most, a positive response of light therapy is usually noted within $4{\sim}5\;days$ and optimal response is obtained within 2 weeks. Generally the relapse of symptom occurs within days of discontinuation of light therapy, so to prevent relapse, light therapy should be continued throughout the winter season for typical seasonal affective disorder. Side effects of light therapy appear to be mild and well tolerated. Several theories for the mechanisms of action of light therapy at the basis of seasonal affective disorder had been suggested but remain still controversial. Further studies on the optimal parameters and the mechanisms of light therapy help us to better understand and treat not only seasonal affective disorders but also chronobiological disorders and nonseasonal affective disorders.

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How Extracellular Reactive Oxygen Species Reach Their Intracellular Targets in Plants

  • Jinsu Lee;Minsoo Han;Yesol Shin;Jung-Min Lee;Geon Heo;Yuree Lee
    • Molecules and Cells
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    • v.46 no.6
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    • pp.329-336
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    • 2023
  • Reactive oxygen species (ROS) serve as secondary messengers that regulate various developmental and signal transduction processes, with ROS primarily generated by NADPH OXIDASEs (referred to as RESPIRATORY BURST OXIDASE HOMOLOGs [RBOHs] in plants). However, the types and locations of ROS produced by RBOHs are different from those expected to mediate intracellular signaling. RBOHs produce O2•- rather than H2O2 which is relatively long-lived and able to diffuse through membranes, and this production occurs outside the cell instead of in the cytoplasm, where signaling cascades occur. A widely accepted model explaining this discrepancy proposes that RBOH-produced extracellular O2•- is converted to H2O2 by superoxide dismutase and then imported by aquaporins to reach its cytoplasmic targets. However, this model does not explain how the specificity of ROS targeting is ensured while minimizing unnecessary damage during the bulk translocation of extracellular ROS (eROS). An increasing number of studies have provided clues about eROS action mechanisms, revealing various mechanisms for eROS perception in the apoplast, crosstalk between eROS and reactive nitrogen species, and the contribution of intracellular organelles to cytoplasmic ROS bursts. In this review, we summarize these recent advances, highlight the mechanisms underlying eROS action, and provide an overview of the routes by which eROS-induced changes reach the intracellular space.

Somatotropic Axis and Nutrition in Young Ruminants around Weaning Time

  • Katoh, K.;Takahashi, T.;Kobayashi, Y.;Obara, Y.
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.7
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    • pp.1156-1168
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    • 2007
  • The somatotropic (GH-IGF-I) axis consists of many hormonal and nutritional factors that control GH release from the somatotrophs in the anterior pituitary. The GH-releasing substances are GHRH and GHS (GHRP or ghrelin), while the GH release-inhibiting substances are somatostatin (SRIF), insulin-like growth factor-I (IGF-I), leptin and glucocorticoids. However, there is evidence showing that nutrition is involved in the control of the somatotropic axis. In addition, weaning is a drastic event for neonates because their alimentary and endocrine circumstances are changed due to the switch, even if gradual, from a liquid milk diet to one composed of such solids as hay and grains. The biological role of ghrelin is one of the hormonal factors that have been focused on ever since ghrelin was discovered at the end of the last century. A 27-amino acid peptide that is mainly synthesized and released from the abomasum epithelium, ghrelin has not been fully evaluated in relation to the somatotropic axis of the ruminant. It has also proven difficult even to investigate the cellular mechanisms of ghrelin action, because this hormone exerts animal-species-dependent actions via a complex set of intracellular signaling pathways. This is also the case for the action of leptin. Another substance, IGF-I, shows a partial inhibitory action on GH secretion in the ruminant. The effect of nutrition is also different among animal species. This is evident by the fact that undernutrition suppresses the circulating GH levels in rodents, but increases it in ruminants and humans. Recently, weaning has been shown to change the postprandial GH responses in ruminants; milk feeding increases, but hay and concentrate feeding suppress, the postprandial circulating GH levels. Even if the postprandial GH level is increased, the ghrelin level is decreased by milk feeding. Macronutrients also possess stimulatory and inhibitory actions on GH secretion in vivo and in vitro. These findings indicate the complexity of the control mechanisms of the somatotropic axis. In the present review, we summarize recent findings on the factors controlling the axis of the ruminant.

Computational Model of a Mirror Neuron System for Intent Recognition through Imitative Learning of Objective-directed Action (목적성 행동 모방학습을 통한 의도 인식을 위한 거울뉴런 시스템 계산 모델)

  • Ko, Kwang-Eun;Sim, Kwee-Bo
    • Journal of Institute of Control, Robotics and Systems
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    • v.20 no.6
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    • pp.606-611
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    • 2014
  • The understanding of another's behavior is a fundamental cognitive ability for primates including humans. Recent neuro-physiological studies suggested that there is a direct matching algorithm from visual observation onto an individual's own motor repertories for interpreting cognitive ability. The mirror neurons are known as core regions and are handled as a functionality of intent recognition on the basis of imitative learning of an observed action which is acquired from visual-information of a goal-directed action. In this paper, we addressed previous works used to model the function and mechanisms of mirror neurons and proposed a computational model of a mirror neuron system which can be used in human-robot interaction environments. The major focus of the computation model is the reproduction of an individual's motor repertory with different embodiments. The model's aim is the design of a continuous process which combines sensory evidence, prior task knowledge and a goal-directed matching of action observation and execution. We also propose a biologically inspired plausible equation model.

Influence of Clonidine on Renal Function of Dogs (Clonidine이 개의 신장기능에 미치는 영향)

  • 고석태;김기환
    • YAKHAK HOEJI
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    • v.27 no.4
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    • pp.271-282
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    • 1983
  • This study is an attempt to study the influence of clonidine, which has a central sympatholytic action, on the renal function in dogs and to elucidate its mechanism of action. Clonidine ($15\mu$g/kg) injected into a cephalic vein of the dog produced a marked increase in urine flow and in amounts of $Na^{+}$ and $K^{+}$ excreted in urine, and clearances of free water and osmolar substance, the reabsorption rates of $Na^{+}$ and $K^{+}$ in renal tubules were significantly decreased. Clonidine ($50.0]mu$g/kg) administered intravenouly elicited a transient reduction in urine flow, along with inhibition of all renal functions. Intravenous clonidine-induced diuretic effect was completely blocked by pretreatment with reserpine, and was lessened by water diuresis. Clonidine ($3.0\mu$g/kg) injected tnto a carotid artery revealed a transient diuresis with a increase in clearance of free water. Clonidine injected into a renal artery showed a significant antidiuretic effect and all functions of an experimental kidney were reduced. Antidiuretic action induced by clonidine given into a renal artery markedly suppressed by pretreatment with reserpine. The above results suggest that clonidine has dual mechanisms: 1) diuretic effect due to the central sympatholytic action and inhibition of release of antidiuretic hormone, and 2) antidiutetic effect indued by indirect symptheic stimulation in the periphery.

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Effects of Phyllostachyos Folium (PF) on solid tumor in mice (죽엽이 생쥐의 복강암에 미치는 영향)

  • Song, Jin-Soo;Park, Soo-Yeon;Choi, Jeong-Hwa;Kim, Jong-Han
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.22 no.2
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    • pp.39-49
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    • 2009
  • Objective : Phyllostachyos Folium (PF) has been used to treat patients with febrile disease consuming the body fluids marked by fever with restlessness, thirst etc. In the theory of herbology, PF can clear away heat and promote the production of the body fluids, relieve restlessness. Recently PF is known to have anti-bacterial, anti-oxidantic effects. Methods : The present study was carried out to investigate the effects of PF on solid tumor in mice in terms of immune-potentiating and direct cytotoxic action of PF in vitro and vivo study. The present author investigated thymocyte and splenocyte proliferation to confirm immune-potentiating activity of PF and also investigated tumor/body weight ratio and survival rates in tumor bearing mice. Result : In this study, administration of PF decreased tumor/body weight ratio significantly, and prolonged survival duration compared to non-treated control. In addition, treatment with PF suppressed proliferation rate of Sarcoma 180 (S-180) cells significantly, and elevated proliferation rates of thymocytes isolated from normal mice. These results were co-related with in vivo study. Conclusion : In conclusion, these results suggest that PF is useful to treat patient with solid tumor, because PF has direct toxic action for tumor cell and immune -potentiating action for T cells. Further study will need to elucidate exact mechanisms related in anti-cancer action of PF.

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