• Title/Summary/Keyword: cytotoxicity of brain cell

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Acetylcholinesterase Inhibitory Activity and Protective Effect against Cytotoxicity of Perilla Seed Methanol Extract (들깨 메탄올 추출물의 acetylcholinesterase 억제활성 및 세포독성 보호효과)

  • Choi, Won-Hee;Um, Min-Young;Ahn, Ji-Yun;Kim, Sung-Ran;Kang, Myung-Hwa;Ha, Tae-Youl
    • Korean Journal of Food Science and Technology
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    • v.36 no.6
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    • pp.1026-1031
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    • 2004
  • Acetylcholinesterase inhibitory activity and protective effect against cytotoxicity of PC 12 cell induced by beta-amyloid protein and glutamate were examined in perilla seed methanol extract and its solvent fractions. Methanol extract of perilla seed showed dose-dependent acetylcholinesterase inhibitory activity, with n-butanol fraction showing strongest activity. Perilla seed methanol extract also decreased glutamate- and ${\beta}-amyloid$ protein $(A{\beta})-induced$ cytotoxicities of PC 12 cells dose-dependently. Formation of TBARS induced by $FeSO_{4^-}H_2O_2$ in rat brain was significantly reduced by perilla seed methanol extract, with strongest protective activity formation of TBARS shown in n-butanol fraction. Results suggest perilla seed methanol extract may attenuate actylcholinesterase activity and cytotoxicity induced by glutamate and ${\beta}-amyloid$ protein through suppression of oxidative stress.

Biostability and Drug Delivery Efficiency of γ-Fe2O3 Nano-particles by Cytotoxicity Evaluation (세포독성 평가를 통한 γ-Fe2O3 나노입자의 생체안정성 및 약물전달효율)

  • Lee, Kwon-Jai;An, Jeung-Hee;Shin, Jae-Soo;Kim, Dong-Hee;Yoo, Hwa-Seung;Cho, Chong-Kwan
    • Korean Journal of Materials Research
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    • v.20 no.3
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    • pp.132-136
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    • 2010
  • This study examined the biostability and drug delivery efficiency of g-$Fe_2O_3$ magnetic nanoparticles (GMNs) by cytotoxicity tests using various tumor cell lines and normal cell lines. The GMNs, approximately 20 nm in diameter, were prepared using a chemical coprecipitation technique, and coated with two surfactants to obtain a water-based product. The particle size of the GMNs loaded on hangamdan drugs (HGMNs) measured 20-50 nm in diameter. The characteristics of the particles were examined by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-TEM) and Raman spectrometer. The Raman spectrum of the GMNs showed three broad bands at 274, 612 and $771\;cm^1$. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay showed that the GMNs were non-toxic against human brain cancer cells (SH-SY5Y, T98), human cervical cancer cells (Hela, Siha), human liver cancer cells (HepG2), breast cancer cells (MCF-7), colon cancer cells (CaCO2), human neural stem cells (F3), adult mencenchymal stem cells (B10), human kidney stem cells (HEK293 cell), human prostate cancer (Du 145, PC3) and normal human fibroblasts (HS 68) tested. However, HGMNs were cytotoxic at 69.99% against the DU145 prostate cancer cell, and at 34.37% in the Hela cell. These results indicate that the GMNs were biostable and the HGMNs served as effective drug delivery vehicles.

Effects of Talmyung-san on the Cultured Rat Myocardiac Cell and Vascular Smooth Muscle Cell (탈명산(奪命散)이 배양심근세포(培養心筋細胞) 및 혈관평골근세포(血管平滑筋細胞)에 미치는 영향(影響))

  • Seong, Gang-Gyeong;Bag, Se-Hong
    • The Journal of Internal Korean Medicine
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    • v.21 no.1
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    • pp.46-54
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    • 2000
  • Objectives : Talmyung-san(TMS) has been used for treatment of brain diseases in Chinese traditional medicine. However, little is known about the mechanism by which TMS rescues brain cells from ischemic damages. To elucidate the protective mechanisms of TMS, we execute experiments. Methods : The effects of TMS on ischemia/reperfusion-induced cytotoxicity and generation of nitric oxide(NO) are investigated in primary neonatal myocardial cells and A7rS, aortic smooth muscle cell line. Results : Ischemia/reperfusion itself induces severe myocardial cell death in vitro. However, treatment of the cells with TMS significantly reduces both ischemia/reperfusion-induced myocardial cell death and LDH release. In addition, pretreatment of TMS before reperfusion recovers the lose of beating rates alter ischemia/reperfusion. For a while, the water extract of TMS stimulates myocardial cells to produce NO in a dose dependent manner and it protects the damage of ischemia/reperfusion-induced myocardial cells. Furthermore, the protective effects of the water extract of TMS is mimicked by treatment of sodium nitroprusside, an exogenous NO donor. NG-monomethyl-L-arginine (NGMMA), a specific inhibitor of nitric oxide synthase(NOS), significantly blocks the protective effects of TMS on the cells after ischemia/reperfusion. In addition, on ischemia the water extract of TMS induce NO in A7r5 cell. Conclusions : Taken together, we suggest that the protective effects of TMS against ischemia/reperfusion-induced myocardial damages may be mediated by NO production of myocardial and vascular smooth muscle cell during ischemic condition.

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Apoptin gene delivery by a PAMAM dendrimer modified with a nuclear localization signal peptide as a gene carrier for brain cancer therapy

  • Bae, Yoonhee;Lee, Jell;Kho, Changwon;Choi, Joon Sig;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.5
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    • pp.467-478
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    • 2021
  • In this study, we aimed to synthesize PAMAMG3 derivatives (PAMAMG3-KRRR and PAMAMG3-HKRRR), using KRRR peptides as a nuclear localization signal and introduced histidine residues into the KRRR-grafted PAMAMG3 for delivering a therapeutic, carcinoma cell-selective apoptosis gene, apoptin into human primary glioma (GBL-14) cells and human dermal fibroblasts. We examined their cytotoxicity and gene expression using luciferase activity and enhanced green fluorescent protein PAMAMG3 derivatives in both cell lines. We treated cells with PAMAMG3 derivative/apoptin complexes and investigated their intracellular distribution using confocal microscopy. The PAMAMG3-KRRR and PAMAMG3-HKRRR dendrimers were found to escape from endolysosomes into the cytosol. The JC-1 assay, glutathione levels, and Annexin V staining results showed that apoptin triggered cell death in GBL-14 cells. Overall, these findings indicated that the PAMAMG3-HKRRR/apoptin complex is a potential candidate for an effective nonviral gene delivery system for brain tumor therapy in vitro.

The Anthocyanin Components and Cytotoxic Activity of Syzygium cumini (L.) Fruits Growing in Egypt

  • Nazif, Naglaa M.
    • Natural Product Sciences
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    • v.13 no.2
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    • pp.135-139
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    • 2007
  • Four anthocyanins were isolated from the acidic alcoholic extract of Syzygium cumini fruits growing in Egypt: Pelargonidin-3-O-glucoside, pelargonidin-3,5-O-diglucoside, cyanidin-3-O-malonyl glucoside, and delphenidin-3-O-glucoside. They were identified by the chromatographic, TLC and PC, and spectral analyses, UV, $^1$H-NMR and FAB/MS. The fruits were found to contain 0.03 gm % anthocyanins calculated on fresh weight basis calculated by spectrophotometric assay. Cytotoxic activity of total alcoholic extract of the fruits was performed against several types of tumor cell lines using the SRB assay. The tested extract exhibited significant cytotoxic activity for MCF7 (breast carcinoma cell line) (IC$_{50}$= 5.9 ${\mu}$g/mL), while the IC$_{50}$ was > 10 ${\mu}$g/mL for both Hela (Cervix carcinoma cell line), HEPG2 (liver carcinoma cell line), H460 (Lung carcinoma cell line) and U251 (Brain carcinoma cell line).

Comparison with Some Antioxidants on Hydroxyl Radical in Mouse Whole Brain Culture

  • Lee, Jeong-Chae;Lim, Kye-Taek;Lee, Ki-Seoup;Jung, Hee-young
    • Toxicological Research
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    • v.14 no.4
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    • pp.541-545
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    • 1998
  • This experiment carried out to compare the protective effects of some antioxidants to hydroxyl radicals in embryonic mouse whole brain tissue culture. The ICR mouse whole brain (13 embryonic day) was cultured in hydroxyl radical system in which radicals were generated by 20 mU / ml glucose oxidase (GO). In this experiment, to make ferrous iron from ferric iron, iron as an accelerator, and ascorbic acid as a reductant were used. For comparison of the protective effects to hydroxyl radicals, antioxidants such as desferrioxamine (DFX), laccase. water or ethanol extracts from Rhus Vemiciflua Stokes (RVS), and $\alpha$-tocopherol were used, because they relate to metal ion. The results of this experiment showed that all antioxidants protected effectively the cytotoxicity from hydroxyl radicals in the brain cultures. More than 70% of cell viabilities among different antioxidants was at 1 mM DFX, 1.43 $\mu\textrm{m}$ laccase, 12.5 $\mu\textrm{m}$ water extract, 12.5 $\mu\textrm{m}$ ethanol extract and 50 $\mu\textrm{m}$ $\alpha$-tocopherol individually, compared with 20 mU/ml GO alone. In comparison to the antioxidative activities of antioxidants, laccase and extracts from RVS showed strong antioxidative effects even at low concentration.

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Cell Death Mediated by Vibrio parahaemolyticus Type III Secretion System 1 Is Dependent on ERK1/2 MAPK, but Independent of Caspases

  • Yang, Yu-Jin;Lee, Na-Kyung;Lee, Na-Yeon;Lee, Jong-Woong;Park, Soon-Jung
    • Journal of Microbiology and Biotechnology
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    • v.21 no.9
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    • pp.903-913
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    • 2011
  • Vibrio parahaemolyticus, which causes gastroenteritis, wound infection, and septicemia, has two sets of type III secretion systems (TTSS), TTSS1 and TTSS2. A TTSS1-deficient vcrD1 mutant of V. parahaemolyticus showed an attenuated cytotoxicity against HEp-2 cells, and a significant reduction in mouse lethality, which were both restored by complementation with the intact vcrD1 gene. V. parahaemolyticus also triggered phosphorylation of mitogen-activated protein kinases (MAPKs) including p38 and ERK1/2 in HEp-2 cells. The ability to activate p38 and ERK1/2 was significantly affected in a TTSS1-deficient vcrD1 mutant. Experiments using MAPK inhibitors showed that p38 and ERK1/2 MAPKs are involved in V. parahaemolyticus-induced death of HEp-2 cells. In addition, caspase-3 and caspase-9 were processed into active forms in V. parahaemolyticus-exposed HEp-2 cells, but activation of caspases was not essential for V. parahaemolyticus-induced death of HEp-2 cells, as shown by both annexin V staining and lactate dehydrogenase release assays. We conclude that secreted protein(s) of TTSS1 play an important role in activation of p38 and ERK1/2 in HEp-2 cells that eventually leads to cell death via a caspase-independent mechanism.

The Regulatory Effect of Zhengan Xifeng-tang on Pro-inflammatory Cytokine in Human Brain Astrocytes (인간 뇌 성상세포에서 진간식풍탕의 사이토카인 조절 효과)

  • Ryu Hyun Hee;Lee Seoung Geun;Lee Key Sang
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.2
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    • pp.490-495
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    • 2004
  • Brain cells produce cytokines and chemokines during the inflammatory process of many neuronal diseases both in animal models and in patients. Inflammatory cytokines are the main responsible for the onset of inflammatory cascade. During the past decade, a growing corpus of evidence has indicated an important role of these cytokines in the development of brain damage. ZhenganXifeng-tang (ZGXFT) is a Korean herbal prescription, which has been successfully applied for the treatment of various neuronal diseases. However, its effect in experimental models remains unknown. Astrocytes are predominant neuroglial cells of the central nervous system and are actively involved in cytokine-mediated events in inflammatory disease. An inflammatory response associated with β-amyloid (Aβ) and interleukin (IL)-1β is responsible for the pathology of inflammation disease. To investigate the biological effect of ZGXFT, the author examined cytotoxicity, effect of cytokines (IL-6 and IL-8) secretion and expression of cyclooxygenase-2 (COX-2) on human astrocytoma cell line U373MG stimulated with IL-1β plus M fragment 25-35 (Aβ [25-35]). ZGXFT by itself had no effect on cell viability on human astrocytoma cells. The secretion of IL-6 and IL-8 was inhibited by pre-treatment with ZGXFT in human astrocytoma cells. In addition, the expression of COX-2 was induced by IL-1β plus AB[25-35] and was partially inhibited by treatment with ZGXFT. The author demonstrates the regulatory effects of inflammatory reactions by ZGXFT in human astrocytes for the first time and suggest the anti-inflammatory effect of ZGXFT may reduce and delay pathologic events of inflammatory disease.

Effects of Samultang on Glutamate-Induced Apoptosis of Hippocampus Cells (사물탕(四物湯)이 Glutamate에 의한 해마세포의 손상에 미치는 영향)

  • Jeong, Dae-Young;Choi, Chul-Won;Moon, Byung-Soon
    • The Journal of Korean Medicine
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    • v.30 no.1
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    • pp.64-75
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    • 2009
  • Objective: This study was designed to investigate the effect of Samultang (SMT) under hippocampus cells ischemia both in vitro and in vivo. Methods: In the in vitro study, HT22 cells, predominantly detected in the cytoplasm, which coincides with the location of the mitochondria, were used as indicators. In the in vivo study, permanent middle cerebral artery occlusion (MCAO) was induced on rats. SMT was given orally 2 h before induction of permanent focal brain ischemic injury. Result: In the in vitro study, SMT had protective effects in glutamate-induced cytotoxicity, which was revealed as apoptosis characterized by chromatic condensation and the loss of mitochondrial membrane potential in HT22 cells. In the in vivo study, TTC (2,3,5-triphenyltetrazolium chloride) staining showed a marked ischemic injury in blood supply territory of the middle cerebral artery (MCA) such as the cerebral cortex and striatum. However, treatment with SMT significantly reduced infarcted volume. SMT increased marked survival of HT22 cells against glutamate-induced cytotoxicity in MTT assay. Conclusion: These results suggest that water extract of SMT provides neuroprotection against ischemic or oxidative injury by inhibition of apoptotic cell death.

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Antidiabetic Drugs and Their Nanoconjugates Repurposed as Novel Antimicrobial Agents against Acanthamoeba castellanii

  • Anwar, Ayaz;Siddiqui, Ruqaiyyah;Shah, Muhammad Raza;Khan, Naveed Ahmed
    • Journal of Microbiology and Biotechnology
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    • v.29 no.5
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    • pp.713-720
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    • 2019
  • Acanthamoeba castellanii belonging to the T4 genotype may cause a fatal brain infection known as granulomatous amoebic encephalitis, and the vision-threatening eye infection Acanthamoeba keratitis. The aim of this study was to evaluate the antiamoebic effects of three clinically available antidiabetic drugs, Glimepiride, Vildagliptin and Repaglinide, against A. castellanii belonging to the T4 genotype. Furthermore, we attempted to conjugate these drugs with silver nanoparticles (AgNPs) to enhance their antiamoebic effects. Amoebicidal, encystation, excystation, and host cell cytotoxicity assays were performed to unravel any antiacanthamoebic effects. Vildagliptin conjugated silver nanoparticles (Vgt-AgNPs) characterized by spectroscopic techniques and atomic force microscopy were synthesized. All three drugs showed antiamoebic effects against A. castellanii and significantly blocked the encystation. These drugs also showed significant cysticidal effects and reduced host cell cytotoxicity caused by A. castellanii. Moreover, Vildagliptin-coated silver nanoparticles were successfully synthesized and are shown to enhance its antiacanthamoebic potency at significantly reduced concentration. The repurposed application of the tested antidiabetic drugs and their nanoparticles against free-living amoeba such as Acanthamoeba castellanii described here is a novel outcome that holds tremendous potential for future applications against devastating infection.