• Title/Summary/Keyword: pro-oxidant activity

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Actinidia arguta Protects Cultured Cerebral Cortical Neurons against Glutamate-Induced Neurotoxicity via Inhibition of $[Ca^{2+}]_i$ Increase and ROS Generation

  • Cho, Jae-Hee;Lee, Hong-Kyu;Seong, Yeon-Hee
    • Natural Product Sciences
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    • v.18 no.1
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    • pp.26-31
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    • 2012
  • Actinidia arguta (Actinidiaceae) has been reported to have several pharmacological effects such as anti-inflammatory, anti-allergic, and anti-oxidant activities. The present study investigated the protective activity of an ethanol extract from the leaf and stem of A. arguta against glutamate-induced neurotoxicity using cultured rat cortical neurons. Exposure of cultured cortical neurons to $500{\mu}M$ glutamate for 12 h triggered neuronal cell death. A. arguta inhibited glutamate-induced neuronal death and apoptosis, which were measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining, respectively. The increase of pro-apoptotic proteins, Bax and c-caspase-3, in glutamate-treated neurons was significantly inhibited by treatment with A. arguta. A. arguta also inhibited $500{\mu}M$ glutamate-induced elevation of intracellular calcium concentration ($[Ca^{2+}]_i$) and reactive oxygen species (ROS) generation, which were measured by fluorescent dyes, Fluo-4 AM and $H_2DCF$-DA, respectively. These results suggest that A. arguta may prevent glutamate-induced apoptotic neuronal death by inhibiting $[Ca^{2+}]_i$ elevation and ROS generation and, therefore, may have a therapeutic role for the prevention of neurodegeneration in cerebral ischemic diseases.

Anti-oxidative Effect of Sapindus mukorossi Fruits Extract in LPS-stimulated macrophages via Activation of Nrf2/HO-1 pathway (LPS가 처리된 대식세포에서 Nrf2/HO-1 경로 활성을 통한 무환자나무 열매 추출물의 항산화 효과)

  • Kim, Dae-Yong
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.5
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    • pp.1306-1313
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    • 2020
  • The aims of this study were to determine the effects of Sapindus mukorossi fruit extracts (SME) on the anti-oxidant activity in LPS-stimulated RAW264.7 macrophages. The results showed that SME significantly reduced the production of ROS in LPS-stimulated RAW264.7 cells. The expression of pro-inflammatory proteins including COX-2 and iNOS were also obviously inhibited by SME in LPS-stimulated RAW264.7 cells. Further studies revealed that SME up-regulated HO-1 and Nrf2 expression. Additionally, SME increased phosphorylation of Akt and GSK-3β. These results suggest that SME could attenuate oxidative stress by activating the Nrf2/HO-1 signaling pathway.

Antioxidant and Apoptotic Effects of an Aqueous Extract of Urtica dioica on the MCF-7 Human Breast Cancer Cell Line

  • Fattahi, Sadegh;Ardekani, Ali Motevalizadeh;Zabihi, Ebrahim;Abedian, Zeinab;Mostafazadeh, Amrollah;Pourbagher, Roghayeh;Akhavan-Niaki, Haleh
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5317-5323
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    • 2013
  • Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of $r^2$=0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an $IC_{50}$ value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.

Antioxidant capacity and Raw 264.7 macrophage anti-inflammatory effect of the Tenebrio Molitor (갈색거저리(Tenebrio Molitor)의 항산화능과 Raw 264.7 대식세포의 항염증 효과)

  • Yu, Jae-Myo;Jang, Jae-Yoon;Kim, Hyeon-Jeong;Cho, Yong-Hun;Kim, Dong-in;Kwon, O-jun;Cho, Yeong-Je;An, Bong-Jeun
    • Food Science and Preservation
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    • v.23 no.6
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    • pp.890-898
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    • 2016
  • The purpose of this paper is to investigate potential anti-inflammatory and anti-oxidant effects of Tenebrio molitor. Macrophage cell response by outside stimulation leads expression of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), $interleukin-1{\beta}$ ($IL-1{\beta}$), and trigger expression of genes which are affected by inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), resulting in formation of inflammatory factors like nitric oxide (NO) and Prostaglandin $E_2$ (PGE2). Cell viability was determined by MTT assay. In order to investigate anti-inflammatory agents, the inhibitory effects on the production of lipopolysaccharide (LPS)-induced NO in RAW 264.7 cells were examined. T. Molitor significantly decreased the production of NO in a dose-dependent manner, and also reduced the expression of iNOS, a COX-2 protein. As a result, the levels of protein such as $PGE_2$, iNOS, COX-2 and MARKs were significantly reduced compared to non-treated group in T. Molitor water extract (TDW) treated group. Also, antioxidant effect of T. Molitor were investigated using DPPH, ABTS+ and superoxide anion radical scavenging activity tests in cell-free system. Antioxidant activity of T. molitor was found low in the DPPH radical scavenging test while high in the ABTS+ and superoxide anion radical scavenging activity tests. These results show that TDW could be an effective anti-pro-inflammatory and anti-oxidant agent.

Targeting Nrf2-Mediated Gene Transcription by Triterpenoids and Their Derivatives

  • Loboda, Agnieszka;Rojczyk-Golebiewska, Ewa;Bednarczyk-Cwynar, Barbara;Zaprutko, Lucjusz;Jozkowicz, Alicja;Dulak, Jozef
    • Biomolecules & Therapeutics
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    • v.20 no.6
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    • pp.499-505
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    • 2012
  • Chemoprevention represents a strategy designed to protect cells or tissues against various carcinogens and carcinogenic metabolites derived from exogenous or endogenous sources. Recent studies indicate that plant-derived triterpenoids, like oleanolic acid, may exert cytoprotective functions via regulation of the activity of different transcription factors. The chemopreventive effects may be mediated through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor. Activation of Nrf2 by triterpenoids induces the expression of phase 2 detoxifying and antioxidant enzymes such as NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) - proteins which can protect cells or tissues against various toxic metabolites. On the other hand, inhibition of other transcription factors, like NF-${\kappa}B$ leads to the decrease in the pro-inflammatory gene expression. Moreover, the modulation of microRNAs activity may constitute a new mechanism responsible for valuable effects of triterpenoids. Recently, based on the structure of naturally occurring triterpenoids and with involvement of bioinformatics and computational chemistry, many synthetic analogs with improved biological properties have been obtained. Data from in vitro and in vivo experiments strongly suggest synthetic derivatives as promising candidates in the chemopreventive and chemotherapeutic strategies.

Healing and preventive effects of low-esterified pectin on liver injury induced by carbon tetrachloride in rats

  • Khotimchenko, Yuri S.;Kolenchenko, Elena A.;Khotimchenko, Maxim Y.;Kovalev, Valeri V.
    • Advances in Traditional Medicine
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    • v.4 no.1
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    • pp.28-36
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    • 2004
  • The purpose of this study was to investigate the pharmacological effects of low-esterified pectin on carbon tetrachloride $(CCL_4)-induced$ hepatotoxicity in rats. The study included two experiments. In the first experiment the animals were given daily $CCL_4$ through gavage for 7 days and then 10, 50, or 250 mg/kg b.w. of pectin for 21 days. At the end of experiment rats were killed within 24 hours. The increased bilirubin level, enhanced alanine aminotransferase and aspartate aminotransferase activity in plasma induced by $CCL_4$ were partly normalized by pectin administration in a dose-dependent manner. The pectin treatment also resulted in significant recovery of $CCL_4-induced$ decrease of the liver glycogen content. In addition, pectin significantly improved $CCL_4-induced$ alterations of pro-oxidant and antioxidant biochemical parameters in liver and plasma compared to those of rats administered $CCL_4$. In the second experiment the animals were given daily 10, 50 or 250 mg/ kg b.w. of pectin for 21 days before a 7-day administration of $CCL_4$. Rats were killed 24 hours after the end of experiment. Pretreatment with pectin before $CCL_4$ administration resulted in significantly inhibited increase of the blood enzymatic activities of alanine and aspartate aminotransferases and bilirubin level in a dose-dependent manner. Also, preliminary administration of pectin prevented elevation of malondialdehyde and conjugated diene levels in liver and plasma as well as a reduction of glutathione content in liver of rats given $CCL_4$. These results suggest that low-esterified pectin exert healing and preventive effects on $CCL_4-induced$ hepatotoxicity in rats.

Inhibitory effect of Hypericum ascyron on pro-inflammatory responses in lipopolysaccharide-induced Raw 264.7 Cells (Lipopolysaccharide로 유도된 Raw 264.7 cell에서 물레나물(Hypericum asctron)의 Pro-inflammatory 억제 효과)

  • Hong, Eun-Jin;Park, Hye-Jin;Kim, Na-Hyun;Jo, Jae-Bum;Lee, Jae-Eun;Lim, Su-Bin;Ahn, Dong-Hyun;Jung, Hee-Young;Cho, Young-Je
    • Journal of Applied Biological Chemistry
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    • v.60 no.4
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    • pp.363-372
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    • 2017
  • Hypericum ascyron has long been used as medicinal plant and recent studies reported that H. ascyron has anti-diabetic, anti-oxidant, and anti-bacterial effects. In this study, inhibitory effect from H. ascyron on pro-inflammatory responses has been investigated. H. ascyron was extracted at optimal extraction condition. Total phenolic contents in water and 90% ethanol were 29.75 and 31.82 mg/g, respectively. Hyaluronidase inhibitory activity of H. ascyron extracts ($50-200{\mu}g/mL$ phenolics) was 0.00-14.81% and 15.33-47.49%, respectively. In cell viability, cell toxicity was shown at concentration of $100{\mu}g/mL$ and $30{\mu}g/mL$ of water and 90% ethanol extract. Therefore, $10-50{\mu}g/mL$ in water extracts and $5-20{\mu}g/mL$ in ethanol extracts was selected each for further study. Inducible nitric oxide synthase (iNOS) derived nitric oxide (NO) and cyclooxygenase (COX)-2-derived prostaglandin $E_2$ ($PGE_2$) protein expression inhibitory effect of extracts were inhibited in a dose dependent manner, significantly. Also, the pro-inflammatory cytokines inhibitory effect such as tumor necrosis $factor-{\alpha}$, nterleukin (IL)-6 and $IL-1{\beta}$ were decreased in the dose dependent manner. The results indicate that H. ascyron extracts reduced inflammatory responses in lipopolysaccharide-induced 264.7 cells via the regulation of the iNOS, COX-2, NO, $PGE_2$, and pro-inflammatory cytokines. Therefore, H. ascyron extracts have significant anti-inflammatory effect and a source as therapeutic materials.

Anti-Oxidative and Anti-Inflammatory Effects of Green Tea Mixture and Dietary Fiber on Liver of High Fat Diet-Induced Obese Rats (고지방 식이로 유도된 비만 흰쥐의 간에서 식이섬유와 녹차혼합물의 항산화 및 항염증 효과)

  • Kim, Jong-Dai;Lee, Byung-Il;Jeon, Yun-Hui;Bak, Jong-Phil;Jin, Hai-Lan;Lim, Beong-Ou
    • Korean Journal of Medicinal Crop Science
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    • v.18 no.4
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    • pp.224-230
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    • 2010
  • This study was conducted to investigate anti-oxidative and inflammatory inhibition effects of green tea and dietary fiber mixture on liver of high fat diet-induced obese rats. 21 male rats were divided into 3 dietary groups and control group (A), high fat diet-induced group (B), and high fat (HF) diet-induced + EQ diet-$S^{(R)}$ diet group (C). Immunoblotting and RT-PCR analysis revealed protein expression, and anti-oxidant analysis revealed MDA (malondialdehyde), GSH (glutathione), and free DPPH radical. As a results, Body weight and food consumption were not significantly different between groups. The levels of MDA and GSH were lower in HF + $EQS^{(R)}$ group than in HF group. Also, the $EQS^{(R)}$ demonstrated to be more effective than HF group for a DPPH radicals scavenging activities. In addition, protein and mRNA level of TNF-$\alpha$ in HF + $EQS^{(R)}$ group showed relatively more potent pro-inflammatory activity inhibition compared to HF group. These results suggest that green tea mixture (EQ diet-$S^{(R)}$) provide positive effects on anti-oxidative and inflammatory inhibition effects on obese animal model or obesity related diseases.

Anti-inflammatory Activities of GyejigaChulBuTang on Lipopolysaccharide-stimulated RAW264.7 Cells (LPS에 의해 자극된 RAW264.7 세포에 대한 계지가출부탕의 항염증활동)

  • Jeong, Min-Jeong;Lee, Seung-Yeon;Yu, Sun-Ae;Kang, Kyung-Hwa
    • The Journal of Pediatrics of Korean Medicine
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    • v.28 no.3
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    • pp.47-58
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    • 2014
  • Objectives GyejigaChulBuTang (GCBT) is a prescription used to treat acute and chronic arthritis in Korea, China, and Japan. This study assessed the anti-inflammatory and anti-oxidant activities of GCBT on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Methods Raw264.7 cells were pretreated with or without GCBT for 1 hour prior to incubation with LPS. Anti-inflammatory activity of GCBT was evaluated with reference to gene expression and production levels of proinflammatory cytokines ($TNF{\alpha}$, IL-$1{\beta}$, IL-6, GM-CSF and $INF{\gamma}$) and inflammatory mediators (iNOS, COX-2, NO and $PGE_2$). In addition, intracellular ROS generation and signal transduction of MAPK family, PI3K/Akt and $I{\kappa}B{\alpha}/NF{\kappa}B$ was investigated. Results Prior treatment with GCBT inhibited elevation of $TNF{\alpha}$, IL-$1{\beta}$, IL-6, GM-CSF, $INF{\gamma}$, NO and $PGE_2$, together with their cognate mRNAs in a dose-dependent manner. Intracellular ROS contents were similarly reduced. These effects were due to inhibition of LPS-induced phosphorylation of MAPK family, PI3K/Akt and $I{\kappa}B{\alpha}$ as well as nuclear translocation of $NF{\kappa}B$. Conclusions GCBT suppresses pro-inflammatory mediators. GCBT has potential in the treatment of juvenile rheumatoid arthritis associated with inflammation.

Methanol Extracts of Codium fragile Induces Apoptosis through G1/S Cell Cycle Arrest in FaDu Human Hypopharynx Squamous Carcinoma Cells

  • Lee, Seul Ah;Park, Bo-Ram;Moon, Sung Min;Kim, Do Kyung;Kim, Chun Sung
    • International Journal of Oral Biology
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    • v.43 no.2
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    • pp.61-68
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    • 2018
  • Codium fragile (Suringar) Hariot is an edible green seaweed that belong to the Codiaceae family and has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria. Methanol extract of codium fragile has anti-oxidant, anti-inflammatory and anti-cancer properties, although the anti-cancer effect on oral cancer has not yet been reported. In this study, we investigated the anti-cancer activity and the mechanism of cell death by methanol extracts of Codium fragile (MeCF) on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that MeCF inhibits cell viability in a dose-dependent manner, and markedly induced apoptosis, as determined by the MTT assay, Live/Dead assay, and DAPI stain. In addition, MeCF induced the proteolytic cleavage of procaspase -3, -7, -9 and poly(ADP-ribose) polymerase(PARP), and upregulated or downregulated the expression of mitochondrial-apoptosis factor, Bax(pro-apoptotic factor), and Bcl-2(anti-apoptotic factor). Futhermore, MeCF induced a cell cycle arrest at the G1/S phase through suppressing the expression of the cell cycle cascade proteins, p21, CDK4, CyclinD1, and phospho-Rb. Taken together, these results indicated that MeCF inhibits cell growth, and this inhibition is mediated by caspase- and mitochondrial-dependent apoptotic pathways through cell cycle arrest at the G1/S phase in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, methanol extracts of Codium fragile can be provided as a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.