• Title/Summary/Keyword: Drug screen

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Screening on Receptor Tyrosine Kinase Inhibitory Activity of Marine Algae-Derived Symbiotic Microorganisms (해조류 공생미생물의 Receptor Tyrosine Kinase 억제효능 검색)

  • Yun, Keum-Ja;Yang, Guohua;Feng, Zhile;Nenkep, Viviane N.;Xavier, Siwe-Noundou;Leutou, Alain S.;Kim, Gun-Do;Cho, Hee-Yeong;Choi, Hong-Dae;Son, Byeng-Wha
    • Korean Journal of Pharmacognosy
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    • v.41 no.1
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    • pp.43-47
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    • 2010
  • In order to screen new receptor tyrosine kinase inhibitor which is expected to be anticancer drug lead, we have investigated receptor tyrosine kinase inhibitory activity on the marine alga-derived symbiotic microorganisms (500 strains). The significant activities (over 70% inhibition at $10\;{\mu}g/ml$) were observed in the extracts of ten strains (Strain No.: MFA018, 019, 206, 242, 325, 335, 343, 344, 354, 356), isolated from marine red algae, five strains (Strain No.: MFA030, 126, 213, 324, 339), isolated from the brown algae, and one strain (Strain No.: MFA272), isolated from the marine green algae, respectively. Among the active strains, MFA019 and 356 showed strong receptor tyrosine kinase inhibitory activity with $IC_{50}$ values of 0.6 and $0.9\;{\mu}g/ml$, respectively.

Regulation of AKT Activity by Inhibition of the Pleckstrin Homology Domain-PtdIns(3,4,5)P3 Interaction Using Flavonoids

  • Kang, Yerin;Jang, Geupil;Ahn, Seunghyun;Lee, Youngshim;Shin, Soon Young;Yoon, Youngdae
    • Journal of Microbiology and Biotechnology
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    • v.28 no.8
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    • pp.1401-1411
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    • 2018
  • The serine-threonine kinase AKT plays a pivotal role in tumor progression and is frequently overactivated in cancer cells; this protein is therefore a critical therapeutic target for cancer intervention. We aimed to identify small molecule inhibitors of the pleckstrin homology (PH) domain of AKT to disrupt binding of phosphatidylinositol-3,4,5-trisphosphate (PIP3), thereby downregulating AKT activity. Liposome pulldown assays coupled with fluorescence spectrometry were used to screen flavonoids for inhibition of the AKT PH-PIP3 interaction. Western blotting was used to determine the effects of the inhibitors on AKT activation in cancer cells, and in silico docking was used for structural analysis and optimization of inhibitor structure. Several flavonoids showing up to 50% inhibition of the AKT PH-PIP3 interaction decreased the level of AKT activation at the cellular level. In addition, the modified flavonoid showed increased inhibitory effects and the approach would be applied to develop anticancer drug candidates. In this study, we provide a rationale for targeting the lipid-binding domain of AKT, rather than the catalytic kinase domain, in anticancer drug development.

Development of Estimation Methods of Skin Oxidation and Evaluation of Anti-Oxidative Effects of Genistein in Topical Formulations

  • Kim, Seong-Yeon;Na, Yeon-Joo;Kim, Dong-Ju;Kim, Yeong-Seok;Kim, Hyeong-Min;Hwang, Sung-Ha;Kwak, Ji-Yeon;Kuh, Hyo-Jeong;Lee, Jae-Hwi
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.3
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    • pp.205-209
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    • 2012
  • The objective of the present study was to establish the method of measurement of hydrogen peroxide and to estimate the anti-oxidative effect of genistein in the skin. UVB induced skin oxidation and anti-oxidative effect of genistein formulations were evaluated by determining levels of hydrogen peroxide. The mechanism involved in the determination of hydrogen peroxide is based on a color reaction between ferric ion ($Fe^{3+}$) and xylenol orange, often called FOX assay and subsequent monitoring of absorbance values of the reactant at 540 nm. The reaction was to some extent pH-dependent and detection sensitivity was greatest at pH 1.75. Genistein liposomal gel demonstrated better anti-oxidative effect with regard to lowering hydrogen peroxide levels elevated by UVB irradiation compared to genistein-suspended gel. A linear relationship has been observed between anti-oxidative effect of genistein and drug deposition in the skin tissue. Genistein liposomal gel resulting in the localization of the drug in the deeper skin led to improved anti-oxidative effect compared to genistein gel. The suggested method for evaluation of oxidation of the skin can be used as a tool to screen effective anti-oxidative agents and their delivery systems acting on the skin.

Integrative applications of network pharmacology and molecular docking: An herbal formula ameliorates H9c2 cells injury through pyroptosis

  • Zhongwen Qi;Zhipeng Yan;Yueyao Wang;Nan Ji;Xiaoya Yang;Ao Zhang;Meng Li;Fengqin Xu;Junping Zhang
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.228-236
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    • 2023
  • Background: QiShen YiQi pills (QSYQ) is a Traditional Chinese Medicine (TCM) formula, which has a significant effect on the treatment of patients with myocardial infarction (MI) in clinical practice. However, the molecular mechanism of QSYQ regulation pyroptosis after MI is still not fully known. Hence, this study was designed to reveal the mechanism of the active ingredient in QSYQ. Methods: Integrated approach of network pharmacology and molecular docking, were conducted to screen active components and corresponding common target genes of QSYQ in intervening pyroptosis after MI. Subsequently, STRING and Cytoscape were applied to construct a PPI network, and obtain candidate active compounds. Molecular docking was performed to verify the binding ability of candidate components to pyroptosis proteins and oxygen-glucose deprivation (OGD) induced cardiomyocytes injuries were applied to explore the protective effect and mechanism of the candidate drug. Results: Two drug-likeness compounds were preliminarily selected, and the binding capacity between Ginsenoside Rh2 (Rh2) and key target High Mobility Group Box 1 (HMGB1)was validated in the form of hydrogen bonding. 2 μM Rh2 prevented OGD-induced H9c2 death and reduced IL-18 and IL-1β levels, possibly by decreasing the activation of the NLRP3 inflammasome, inhibiting the expression of p12-caspase1, and attenuating the level of pyroptosis executive protein GSDMD-N. Conclusions: We propose that Rh2 of QSYQ can protect myocardial cells partially by ameliorating pyroptosis, which seems to have a new insight regarding the therapeutic potential for MI.

DNA and Proteomic Analysis of Ginseng Radix Rubra Herbal-acupuncture Solution(GRR-HAS) on Gene Expression in HepG2 Carcinomar Cells (홍삼약침액(紅蔘藥鍼液)의 DNA와 단백질 발현(發顯)에 미치는 영향(影響))

  • Won, Eun-Ju;Lee, Bong-Hyo;Lim, Seong-Chul;Jung, Tae-Young;Seo, Jung-Chul;Lee, Kyung-Min
    • Journal of Acupuncture Research
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    • v.23 no.3
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    • pp.177-190
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    • 2006
  • Objectives : It has long been known about the anticancer effect of GRR-HAS, however, it has not been systemically determined the differentially regulated genes by GRR-HAS in cancer cells. The purpose of this study is to screen the GRR-HAS mediated differentially expressed genes in cancer cells such as HepG2 hepatoma cell lines. Oligonucleotide microarray and proteomic approaches were employed to screen the differential expression genes. Methods : GRR~HAS was prepared by boiling and stored at $-70^{\circ}C$ until use. Cells were treated with various concentrations of GRR-HAS (0.1, 0.5, 1.5, 10, $20mg/m{\ell}$) for 24 h. Cell toxicity was tested by MTT assay. To screen the differentially expressed genes in cancer cells, cells were treated with $1.5mg/m{\ell}$ of GRR-HAS. For oligonucleotide microarray assay, total RNA was used for gene expression analysis using oligonucleotide genechip (Human genome Ul33 Plus 2.0., Affimatrix Co.). For proteomic analysis, total protein was analyzed by 2D gel electrophoresis and Q-TOF mass spectrometer. Results : It has no cytotoxic effects on both HepG2 cells in all concentrations(0.1, 0.5, 1.5, 10,$20mg/m{\ell}$). In oligonucleotide microarray assay, the number of more than twofold differentially regulated known genes was 320 with 6 up-regulated and 314 down-regulated genes in HepG2 cells. In proteomic analysis, three spots were identified by 2D-gel electrophoresis and Q-TOF analysis. One down -regulated protein was protein disulfide isomerase and up-regulated proteins were fatty acid binding protein 1 and 14-3-3 gan1lTIa protein by $1.5mg/m{\ell}$ of CRR-HAS. Discussion : This study showed the comprehensive gene expression analysis using oligonucleotide microarray for the screening of GRR-HAS mediated differentially regulated genes. These results will provide a better application of GRR-HAS in cancer field and drug target development.

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Identification of New Potential APE1 Inhibitors by Pharmacophore Modeling and Molecular Docking

  • Lee, In Won;Yoon, Jonghwan;Lee, Gunhee;Lee, Minho
    • Genomics & Informatics
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    • v.15 no.4
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    • pp.147-155
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    • 2017
  • Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of APE1 could provide a seed for the development of improved anticancer drugs. For this purpose, we first classified known inhibitors of APE1. According to the classification, we constructed two distinct pharmacophore models. We screened more than 3 million lead-like compounds using the pharmacophores. Hits that fulfilled the features of the pharmacophore models were identified. In addition to the pharmacophore screen, we carried out molecular docking to prioritize hits. Based on these processes, we ultimately identified 1,338 potential inhibitors of APE1 with predicted binding affinities to the enzyme.

Taxol Production by an Endophytic Fungus, Fusarium redolens, Isolated from Himalayan Yew

  • Garyali, Sanjog;Kumar, Anil;Reddy, M. Sudhakara
    • Journal of Microbiology and Biotechnology
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    • v.23 no.10
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    • pp.1372-1380
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    • 2013
  • Different endophytic fungi isolated from Himalayan Yew plants were tested for their ability to produce taxol. The BAPT gene (C-13 phenylpropanoid side chain-CoA acetyl transferase) involved in the taxol biosynthetic pathway was used as a molecular marker to screen taxol-producing endophytic fungi. Taxol extracted from fungal strain TBPJ-B was identified by HPLC and MS analysis. Strain TBPJ-B was identified as Fusarium redolens based on the morphology and internal transcribed spacer region of nrDNA analysis. HPLC quantification of fungal taxol showed that F. redolens was capable of producing $66{\mu}g/l$ of taxol in fermentation broth. The antitumour activity of the fungal taxol was tested by potato disc tumor induction assay using Agrobacterium tumefaciens as the tumor induction agent. The present study results showed that PCR amplification of genes involved in taxol biosynthesis is an efficient and reliable method for prescreening taxol-producing fungi. We are reporting for the first time the production of taxol by F. redolens from Taxus baccata L. subsp. wallichiana (Zucc.) Pilger. This study offers important information and a new source for the production of the important anticancer drug taxol by endophytic fungus fermentation.

Screening of Radical Scavenging Activity from the Marine-Derived Fungus (해양균류의 라디칼 소거활성 검색)

  • Li, Xi Feng;Li, Yong;Nam, Ki-Wan;Kim, Dong-Soo;Choi, Hong-Dae;Son, Byeng-Wha
    • Korean Journal of Pharmacognosy
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    • v.33 no.3 s.130
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    • pp.219-223
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    • 2002
  • In order to screen new radical scavenging principle which is expected to be antiaging drug lead, we have isolated 160 strains of the marine-derived fungi and investigated 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity for their acetone extracts. The significant activities (>50% Inhibition) were observed in 8 strains of fungi (MFA006, MFA0l4, MFA040, MFA133, MFA139, MFA143, MFA148, MFA153), and among them, MFA153 (Aspergillus parasiticus) showed the most significant radical scavenging activity. The active components were purified by assay-guided isolation to yield two known benzyl alcohols, l53B3 (1) and l53B4 (2), and their structures were determined by physicochemical evidence. Two compounds (1,2) showed the significant radical scavenging activity with $IC_{50}$ values of 0.6 and $1.4{\mu}M$ against DPPH, respectively.

Effects of Ukgansan (Yokukansan in Japanese, Yigansan in chinese) on the Locomotor Velocity and Glutamate-Induce Paroxysm in Planarian (Planarian 모델을 이용한 억간산의 항발작 효과)

  • Park, Woong;Yoo, Du Man;So, June No
    • KSBB Journal
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    • v.29 no.1
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    • pp.67-71
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    • 2014
  • Planaria were recently reported to be a simple and sensitive model to investigate the mechanistic aspect of seizure and to screen potential anticonvulsants. Using planarian model, we analyzed the pharmacological effect of ukgansan (UGS), an oriental herbal medicine containing seven medicinal herbs, on the planarian locomotor velocity (pLMV) and glutamate-induced seizure-like activity (pSLA). To test whether D. japonica is suitable for studying anti-seizure agents, we investigated the effect of glutamate on pLMV and pSLA in D. japonica. In the present study we first confirmed that pSLA in D. japonica was induced by L-glutamate. Glutamate significantly produced pSLA in a dose dependent manner, but did not affect pLMV. These glutamate-induced paroxysms were decreased by antiepileptic drug, topiramate. A similar inhibitory effect on glutamate-induced pSLA was observed after the treatment of UGS. The present results suggest that UGS and its active constituents possess useful substance inhibiting seizure in planarian and that D. japonica provides a convenient model to search active herbs containing anti-seizure activity.

Reliability and validity of free software for the analysis of locomotor activity in mice

  • Hong, Yoo Rha;Moon, Eunsoo
    • Journal of Yeungnam Medical Science
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    • v.35 no.1
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    • pp.63-69
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    • 2018
  • Background: Kinovea software that tracking semi-automatically the motion in video screen has been used to study motion-related tasks in several studies. However, the validation of this software in open field test to assess locomotor activity have not been studied yet. Therefore, this study aimed to examine the reliability and validity of this software in analyzing locomotor activities. Methods: Thirty male Institute Cancer Research mice were subjected in this study. The results examined by this software and the classical method were compared. Test-retest reliability and inter-rater reliability were analyzed with Pearson's correlation coefficient and intraclass correlation coefficient (ICC). The validity of this software was analyzed with Pearson's correlation coefficient. Results: This software showed good test-retest reliability (ICC=0.997, 95% confidence interval [CI]=0.975-0.994, p<0.001). This software also showed good inter-rater reliability (ICC=0.987, 95% CI=0.973-0.994, p<0.001). Furthermore, in three analyses for the validity of this software, there were significant correlations between two methods (Pearson's correlation coefficient=0.928-0.972, p<0.001). In addition, this software showed good reliability and validity in the analysis locomotor activity according to time interval. Conclusion: This study showed that this software in analyzing drug-induced locomotor activity has good reliability and validity. This software can be effectively used in animal study using the analysis of locomotor activity.