• Title/Summary/Keyword: Mechanism of action

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Effects of Saenghyetang on Learning and Memory Performances in Mice (생혜탕(生慧湯)이 흰쥐의 학습(學習)과 기억(記憶)에 미치는 영향(影響))

  • Yu Geum-Ryoung;Chang Gyu-Tae;Kim Jang-Hyeon
    • The Journal of Pediatrics of Korean Medicine
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    • v.15 no.1
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    • pp.77-104
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    • 2001
  • The effects of the oriental herbal medicine Saenghyetang(SHT, 生慧湯), which consists of Rehmanniae Radix (熟地黃 九蒸: was made by 9th steam) 40g, Corni Fructus(山茱黃) 16g, Polygalae Radix(遠志) 8g, Zizyphi Spinosae Semen(酸棗仁) 2g, Biotae Semen(柏子仁 去油: oil ingredient was removed) 20g, Poria Cocos(茯笭) 12g, Ginseng Radix(人蔘) 12g, Acori Graminei Rhizoma(石菖蒲) 2g, Sinapis Semen(白芥子) 8g, on learning ability and memory were investigated. Hot water extract(HWE) and ethanol extract(EE) from SHT were used for the studies. Learning ability and memory are related to modifications of synaptic strength among neurons that interactive. Enhanced synaptic coincidence detection leads to improved learning ability and memory. If the NMDA receptor, a synaptic coincidence detector, acts as a graded switch for memory formations, enhanced signal detection by NMDA receptors should enhance learning ability and memory. It was shown that NR2B was increased in the forebrains of oriental medicine-administrated mice, leading to enhanced activation of NMDA receptors and facilitating synaptic potentiation in response to stimulation at 10-100 Hz. These HWE-SHT treated mice exhibited that superior ability in learning and memory when performing various behavioral tasks, showing that NR2B is enhanced by HWE-SHT treatment and also is critical in gating the age-dependent threshold for plasticity and memory formation. NMDA receptor-dependent modifications, which were mediated in part by HWE administration, of synaptic efficacy, therefore, represent a mechanism for associative learning ability and memory. Results suggest that oriental medical enhancement of NR2B contributes to increase intelligence and memory in mammals On the other hand, to examine the effects of EE-SHT on the learning ability and memory in experimental mice, EE-SHT was tested on passive and active avoidance responses. The EE-SHT ameliorated the memory retrieval deficit induced by ethanol in mice, but not other memory impairments. EE-SHT(10, 20mg/100 g, p.o.) did not affect the passive avoidance responses of normal mice in the step through and step down tests, the conditioned and unconditioned avoidance responses of normal mice in the shuttle box, lever press performance tests and the ambulatory activity of normal mice in a normal condition. However, EE-SHT at 20 mg/kg significantly decrease the spontaneous motor activity during the shuttle box test, and also to extend the sleeping time induced by pentobarbital in mice. These results suggest that SHT has an ameliorating effect on memory retrieval impairments and a weak tranquilizing action.

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Choi Han-gi's Change of Ontological and Epistemological Paradigm (최한기의 존재와 인식에 관한 패러다임의 전환)

  • Rhee, Myung-Su
    • The Journal of Korean Philosophical History
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    • no.57
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    • pp.9-30
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    • 2018
  • The paradigm of existence and recognition was changed in the context of modernity in Choi Han-gi's thought, in which the resource of all things and all affairs was not li but ki and li could be guessed from ki. And there are lis in the sphere of recognition as well as in that of existence in Choi Han-gi's thought, which might be different from traditional thought system such as Neo-Confutionism. li is called Yuhaenguili in his ontological theory and Chucheukuili as one epistemological part. At anyhow there are many lis, which may be approached as the meaning of mechanism, in his philosophy. Besides there are, not only ontologically but also epistemologically, energetic factors, named as Unhwaki, whch are generating, moving, changing and altering. In his Kihak as an ki categorical thought, above all one's experience is of importance. He believed moral act, for example the expose of saving mind that was called Cheukeunjisim by Mencius, could be derived from social experience or contact. And he thought that the recognition of moral act might be achieved by the action of mysterious energy names as sinki of the essence of mind. Like these aspects, all things and all ones have their active, movable, and changeable natures in the sphere of both existence and recognition in Choi Han-gi's thought. In this way he got out of the previous ideas and presented practical and modern way of life to us.

Sulfasalazine Induces Apoptosis and Cell Cycle Arrest in RAW 264.7 Macrophages (마우스 대식세포에서 설파살라진의 세포사멸 및 세포주기 정체에 미치는 영향 연구)

  • Seong Mi Kim;Sohyeon Park ;Jin-Kyung Kim
    • Journal of Life Science
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    • v.33 no.10
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    • pp.767-775
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    • 2023
  • Sulfasalazine is a disease-modifying antirheumatic abiotic agent. It is a derivative of aminosalicylic acid and has been used for the treatment of various inflammatory diseases, such as rheumatoid arthritis, ulcerative colitis, and Crohn's disease, since it was first synthesized in 1941 and approved as a medicine in the United States in 1950. However, its mechanism of action has not yet been clearly identified. In this study, the effects of sulfasalazine on cell survival, apoptosis, and cell cycle progression in macrophages, which are major immune cells that regulate inflammatory responses, were investigated using mouse macrophage RAW 264.7 cells. Sulfasalazine inhibited the viability of RAW 264.7 cells in a dose-dependent manner, starting at a concentration of 0.25 mM. Annexin-V staining was used to confirm that the decrease in cell viability was due to apoptosis, and the number of Annexin-V-positive cells increased significantly at a concentration of 0.25 mM or higher. The effect of sulfasalazine on the expression of key proteins that regulate the G0/G1 phase of the cell cycle was also investigated. Sulfasalazine treatment significantly increased the expression of the cyclin-dependent kinase inhibitors p21 and p27 in RAW 264.7 cells. Although sulfasalazine is frequently used as a control drug in studies on inflammatory diseases, such as inflammatory colitis and rheumatoid arthritis, studies on its effect on macrophages are very limited. Therefore, the results of this study are expected to provide vital information on the use of sulfasalazine as a disease treatment.

Heat Shock Protein Augmentation of Angelica gigas Nakai Root Hot Water Extract on Adipogenic Differentiation in Murine 3T3-L1 Preadipocytes

  • Lumbera, Wenchie Marie L.;Cruz, Joseph dela;Yang, Seung-Hak;Hwang, Seong Gu
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.3
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    • pp.419-427
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    • 2016
  • There is a high association of heat shock on the alteration of energy and lipid metabolism. The alterations associated with thermal stress are composed of gene expression changes and adaptation through biochemical responses. Previous study showed that Angelica gigas Nakai (AGN) root extract promoted adipogenic differentiation in murine 3T3-L1 preadipocytes under the normal temperature condition. However, its effect in heat shocked 3T3-L1 cells has not been established. In this study, we investigated the effect of AGN root hot water extract in the adipogenic differentiation of murine 3T3-L1 preadipocytes following heat shock and its possible mechanism of action. Thermal stress procedure was executed within the same stage of preadipocyte confluence (G0) through incubation at $42^{\circ}C$ for one hour and then allowed to recover at normal incubation temperature of $37^{\circ}C$ for another hour before AGN treatment for both cell viability assay and Oil Red O. Cell viability assay showed that AGN was able to dose dependently (0 to $400{\mu}g/mL$) increase cell proliferation under normal incubation temperature and also was able to prevent cytotoxicity due to heat shock accompanied by cell proliferation. Confluent preadipocytes were subjected into heat shock procedure, recovery and then AGN treatment prior to stimulation with the differentiation solution. Heat shocked preadipocytes exhibited reduced differentiation as supported by decreased amount of lipid accumulation in Oil Red O staining and triglyceride measurement. However, those heat shocked preadipocytes that then were given AGN extract showed a dose dependent increase in lipid accumulation as shown by both evaluation procedures. In line with these results, real-time polymerase chain reaction (RT-PCR) and Western blot analysis showed that AGN increased adipogenic differentiation by upregulating heat shock protection related genes and proteins together with the adipogenic markers. These findings imply the potential of AGN in heat shock amelioration among 3T3-L1 preadipocytes through heat shock factor and proteins augmentation and enhanced adipogenic marker expression.

Effect of Retinoids on Human Breast Cancer Cells (인체 유방암 세포에서 retinoids의 영향에 대한 연구)

  • 윤현정;신윤용;공구
    • Environmental Mutagens and Carcinogens
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    • v.24 no.2
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    • pp.51-66
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    • 2004
  • Retinoids, better known as vitamin A, have been reported to inhibit the growth of several breast cancer cell lines in culture and to reduce breast tumor growth in animal models. Furthermore, retinoids can augment the action of other breast cancer cell growth inhibitors both in vitro and in vivo. Clinically, interest has increased in the potential use of retinoids for the prevention and treatment of human breast cancer. We have examine the effect of all-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) on human breast cancer cell(MCF-10A, T47-D, MCF-7) proliferation using MTT assay and cell cycle analysis(FACS). Overexpression of cyclin D1 protein is observed in the majority of breast cancers, suggesting that dysregulated expression of cyclin D1 might be a critical event in breast cancer carcinogenesis. We investigated whether tRA and 9-cis RA might affect expression of cyclin D1 on human breast cancer cells(MCF-10A, T47-D, MCF-7) using RT-PCR and west-ern bolt. In MCF-10A cells, either tRA or 9-cis RA treatment did not affect the cell proliferation. In T47-D cells and MCF-7 cells, either tRA or 9-cis RA treatment showed the inhibition of the cell proliferation over control cells and also inhibit the estrogen stimulated cell proliferation when it was given together with estrogen. The effect of retinoids was dose- and time- dependent. T47-D cells treated with 1.0 $\muM$ tRA undergo G0/G1-phase arrest by Day 5. MCF-7 cells treated with 1.0 $\muM$ tRA undergo S-phase arrest by Day 5. All-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) inhibited the cyelin D1 mRNA and protein expression levels of human MCF-7 and T47-D breast carcinoma cells in vitro. The data indicate that retinoids can reduce cyclin D1 expression levels in a variety of breast cell lines in vitro and result in inhibition of cell proliferation. tRA-mediated growth inhibition and cyclin D1 expression inhibition is more potent than 9-cis RA mediated that. tRA-mediated inhibition effect is more potent on T47-D cells than on MCF-7 cells. Our data suggest that retinoids activity is different according to property of cell lines. Future chemoprevention of breast cancer studies using retinoids will be necessary to determine the mechanism of the retinoids-mediated growth inhibition.

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Effects of Watering Method and BA Concentration on Growth and Morphological Characteristics of Mungbean Sprouts (관수방법과 BA 처리농도가 숙주나물의 생장과 형태에 미치는 영향)

  • Ryu Yeong-Seop;Hong Dong-Oh;Lee Chang-Woo;Kim Hong-Young;Kang Jin-Ho
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.51 no.3
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    • pp.204-208
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    • 2006
  • Utilization of synthetic benzyladenine (BA) for bean sprout production should be reduced or minimized because of elevating production cost and not ascertaining action mechanism to human body. The study was done to compare the effects of BA concentrations under different watering methods (overspraying or underwatering) on growth and morphological characteristics of mungbean sprouts. Seeds of cv. Zhong-Lu 1 were soaked for 5 hours in the solutions with different BA concentrations (0, 10, 20, 30, 40, 50 ppm) before 4 hour aeration, and then were cultured for 6 days by both watering systems. Their morphological characters, fresh and dry weights were measured. Regardless of watering methods, lateral roots were sharply dropped over 30 ppm BA concentrations, and hypocotyl, root and total lengths were shortened with increased BA concentrations although ratios of hypocotyl to root lengths and hypocotyl diameters were enlarged with their increment. Total fresh weights were increased up to 20 ppm in overspraying method but up to 30 ppm in underwatering method mainly due to increment of hypocotyl fresh weights. The sprouts were faster grown in overspraying method than in underwatering method because the former showed longer lengths of hypocotyl and root, and total fresh weights.

Forskolin-Induced Potentiation of Catecholamine Secretion Evoked By Ach, DMPP, McN-A-343 and Excess $K^+$ From the Rat Adrenal Gland (Forskolin의 흰쥐적출관류부신으로 부터 Ach, Excess $K^+$, DMPP, McN-A-343에 의한 Catecholamine 분비효과의 증강작용)

  • Lim, Dong-Yoon;Kim, Won-Shik;Choi, Cheol-Hee
    • The Korean Journal of Pharmacology
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    • v.27 no.2
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    • pp.167-181
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    • 1991
  • The present study was an attempt to investigate the effect of forskolin on secretion of catecholamines (CA) evoked by Ach, excess $K^+$, DMPP, McN-A-343 and caffeine from the isolated perfused rat adrenal glands and to elucidate its mechanism of action. The perfusion with forskolin (1.0 uM) for 1 min into the adrenal vein enhanced markedly the secreation of CA evoked by Ach (50 ug), excess $K^+$ (56 mM) DMPP (100 uM) and by caffeine (0.3 mM) but did not that by McN-A-343. Forskolin alone did not potentiate the CA secretion. Moreover, forskolin augmented the CA release evoked by the above same stimulation even in the absence of extracellular calcium. The 1 min perfusion of 300 uM-dibutyryl cyclic AMP (DBcAMP), which is known to increase cyclic AMP levels, led to enhancement of Ca secretion evoked by Ach, excess $K^+$ and DMPP but did not that by McN-A-343 and caffeine. DBcAMP by itself also did not augment the CA secretion. In the calcium-free medium DBcAMP significantly enhanced the CA secretion by the same stimulation, except for the case of McN-A-343. These experimental results suggest that forskolin activates adenylate cyclase, resulting the elevation of cyclic AMP which may potentiate cholinergic nicotinic receptor-mediated and also depolarization-dependent CA secretion and that it may alter the intracellular calcium homeostasis in the rat adrenal glands.

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Autocrine Regulation of Gonadotropin-releasing Hormone (GnRH) Operates at Multiple Control levels of GnRH Gene Expression in GT1-1 Neuronal Cells

  • Jin Han;Sehyung Cho;Woong Sun;Kyungjin Kim
    • Animal cells and systems
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    • v.2 no.4
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    • pp.483-488
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    • 1998
  • We previously found that a potent gonadotropin-releasing hormone (GnRH) agonist, buserelin, decreases GnRH promoter activity together with GnRH mRNA level, providing evidence for an autoregulatory mechanism operating at the level of GnRH gene transcription in immortalized GT1-1 neuronal cells. To examine whether agonist-induced decrease in GnRH mRNA level requires the continuous presence of buserelin, we performed a pulse-chase experiment of buserelin treatment. Short-term exposure (15 min) of GT1-1 neuronal cells to buserelin ($10{\mu}M$) was able to decrease GnRH mRNA levels when determined 24 h later. When GT1-1 cells were treated with buserelin ( $10{\mu}M$) for 30 min and then incubated for 1, 3, 6, 12, 24, and 48 h after buserelin removal, a significant decrease in GnRH mRNA levels was observed after the 12 h incubation period. These data indicate that inhibitory signaling upon buserelin treatment may occur rapidly, but requires a long time (at least 12 h) to significantly decrease the GnRH mRNA level. To examine the possible involvement of de novo synthesis and/or mRNA stability in buserelin-induced decrease in GnRH gene expression, actinomycin D ($5{\mu}m/ml$), a potent RNA synthesis blocker, was co-treated with buserelin. Actinomycin D alone failed to alter basal GnRH mRNA Revel, but blocked the buserelin-induced decrease in GnRH mRNA level at 12 h of post-treatment. These data suggest that buserelin may exert its inhibitory action by altering the stability of GnRH mRNA. Moreover, a polvsomal RNA separation by sucrose gradient centrifugation demonstrated that buserelin decreased the translational efficiency of the transcribed GnRH mRNA. Taken together, these results clearly indicate that GnRH agonist buserelin acts as an inhibitory signal at multiple levels such as transcription mRNA stability, and translation.

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Inhibitory Effects of Gardenia jasminoides var. radicans Makino on HIV-1 Enzymes and Prediction of Inhibitory Factor by QSAR (꽃치자나무 추출물의 HIV-1 효소 억제 활성과 QSAR에 의한 활성인자 예측)

  • Yu, Young-Beob
    • Korean Journal of Plant Resources
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    • v.27 no.1
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    • pp.22-28
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    • 2014
  • In this study, we conducted the anti-HIV-1 enzymes assay in vitro and its active components were predicted by QSAR in silico for the elucidation of action mechanism on anti-HIV of natural resources. The extracts of Gardenia jasminoides var. radicans Makino were tested for their inhibitory effects on the reverse transcriptase (RT), protease and ${\alpha}$-glucosidase. In the enzyme inhibition assay, the methanol extracts of Gardenia jasminoides var. radicans Makino stem showed a strong activity of 32.5% on the enzyme activity to cleave an oligopeptide, resembling one of the cleavage sites in the viral polyprotein which can only be processed by HIV-1 protease. Moreover the methanol extracts of stem exhibited alpha-glucosidase inhibitory activities of 26.1%. The methanol extracts ($100{\mu}g/ml$) of stem showed a weak activity of 13.4% on anti-HIV-1 RT using Enzyme Linked Oligonucleotide Sorbent Assay (ELOSA) method. However, all extracts of leaf and stem didn't exhibit the HIV-1-induced cytopathic effects with IC (inhibitory concentration) of $100{\mu}g/ml$ in HIV-1-infected human T-cell line. From these results, it is suggested that Gardenia jasminoides var. radicans Makino extracts may possibly be involved in the inhibition of reverse transcriptase, protease and alpha-glucosidase but can't vitally concerned with the viral replication in vitro.

Protective Effect of Dopaol β-D-glucoside Isolated from East Asian Monk'shood on Cisplatin-Induced Nephrotoxicity (한라돌쩌귀로부터 분리된 Dopaol β-D-glucoside의 신장독성 보호효과)

  • Nho, Jong Hyun;Jung, Ja Kyun;Jung, Ho Kyung;Jang, Ji Hun;Jung, Da Eun;Lee, Ki Ho;Kim, A Hyeon;Sung, Tae Kyoung;Park, Ho;Cho, Hyun Woo
    • Korean Journal of Medicinal Crop Science
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    • v.25 no.4
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    • pp.231-237
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    • 2017
  • Background: Cisplatin is one of the most extensively used chemotherapeutic agents for the treatment of cancer, including bladder, and ovarian cancers. However, it has been shown to induce nephrotoxicity, despite being an outstanding anti-cancer drug. In this study, we investigated the protective effect of dopaol ${\beta}$-D-glucoside (dopaol) on cisplatin-induced nephrotoxicity. Methods and Results: To confirm the protective effect of dopaol on cisplatin-induced nephrotoxicity, HK-2 cells were treated with $20{\mu}M$ cisplatin and $80{\mu}M$ dopaol. Cisplatin increased apoptosis, caspase-3 activity and mitochondrial dysfunction; however pretreatment with $80{\mu}M$ dopaol successfully attenuated apoptosis, caspase-3 activity and mitochondrial dysfunction. To evaluate the protective effect dopaol on cisplatin-induced nephrotoxicity in vivo, we used an animal model (balb/c mice, 20 mg/kg, i.p. once/day for 3 day). The results were similar to those obtained using HK-2 cells; renal tubular damage and neutrophilia induced by cisplatin reduced following dopaol injection (10 mg/kg, i.p. once/day for 3 day). Conclusions: These results indicate that dopaol treatment reduced cisplatin-induced nephrotoxicity in vitro and in vivo, and can be used to treat cisplatin-induced nephrotoxicity. However, further studies are required to determine the toxicity high dose dopaol and the signal pathways involved in its mechanism of action in animal models.