• Title/Summary/Keyword: Cytotoxic effects

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Effects on Redox Status and NF-${\kappa}B$ Signaling by Ojunghwan (오정환(五精丸)이 ob/ob mouse에서 Redox Status 및 NF-${\kappa}B$ Signaling에 미치는 영향)

  • Baek, Ki-Beom;Jeong, Ji-Cheon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.5
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    • pp.1202-1209
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    • 2008
  • Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}\;{O_2}^-$) and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the effects of Ojunghwan on the generation of peroxynitrite ($ONOO^-$), nitric oxide (NO) and superoxide anion radical (${\cdot}\;{O_2}^-$), and on the expression of $NF-{\kappa}B$-dependent inflammatory proteins in ob/ob mice. Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received the standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Ojung-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blot was performed using anti-phospho $I{\kappa}B-{\alpha}$, $anti-IKK-{\alpha}$, $anti-NF-{\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-VCAM-1 and anti-MMP-9 antibodies, respectively. Ojunghwan inhibited the generation of $ONOO^-$, NO and ${\cdot}\;{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}\;{O_2}^-$ and $PGE_2$ were inhibited in the Ojunghwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas that were improved in the Ojunghwan-administered groups. Ojunghwan inhibited the expression of $phospho-I{\kappa}B-{\alpha}$, $IKK-{\alpha}$, $NF-{\kappa}B$ (p50, p65), COX-2, iNOS, VCAM-1 and MMP-9 genes. These results suggest that Ojunghwan is an effective scavenger of $ONOO^-$, ${\cdot}\;{O_2}^-$, NO and $PGE_2$, and has an inhibitory effect on the expression of $NF-{\kappa}B$-dependent inflammatory genes in ob/ob mice. Therefore, Ojunghwan might be used as a potential therapeutic drug against the inflammation process and inflammation- related diseases.

Effects of Quercetin on $TNF-{\alpha}-Induced$ Cytokine Secretion and Nitric Oxide Production in MC3T3-E1 Osteoblastic Cells

  • Jeon, Young-Mi;Kim, Beom-Tae;Son, Young-Ok;Kook, Sung-Ho;Lee, Keun-Soo;Kim, So-Soon;Lim, Ji-Young;Kim, Jong-Ghee;Lee, Jeong-Chae
    • Natural Product Sciences
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    • v.11 no.2
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    • pp.103-108
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    • 2005
  • Bioflavone quercetin is thought to have an important role to inhibit bone loss by affecting osteoclastogenesis and regulating a number of systemic and local factors such as hormones and cytokines. In this study, we examined how quercetin acts on cytokine production and mineralization of osteoblast in the presence of tumor necrosis factor-alpha $(TNF-{\alpha})$ which has been known to play a pivotal role in bone metabolic diseases. Quercetin inhibited $TNF-{\alpha}-induced$ secretion of $IFN-{\gamma}$ and IL-6 in differentiated MC3T3-E1 cells. As indicated by the markers that are characteristics of the osteoblast phenotype, such as alkaline phosphatase (ALP) activity and calcium deposition, quercetin treatment slightly prevented the $TNF-{\alpha}-induced$ dramatic inhibition of differentiation and mineralization of MC3T3-E1 cells. Further, quercetin inhibited the production of nitric oxide induced by $TNF-{\alpha}$ in the cells. Collectively, our findings indicate that quercetin inhibites $TNF-{\alpha}-induced$ secretion of inflammatory cytokines in differentiated MC3T3-E1 cells without any cytotoxic effects.

Comparison of Anti-oxidative and Anti-inflammatory Effect of Atractylodes Interspecific Hybrid Cultivar Roots (삽주 육성품종 뿌리의 항산화 및 항염증 효과 비교)

  • Jeong, Hyeon Soo;Jeong, Jin Tae;Lee, Jeong Hoon;Park, Chun Geon;Choi, Je Hun;Jang, Gwi Yeong;Kim, Jang Wook;Chang, Jae Ki;Kim, Dong Hwi;Lee, Seung Eun
    • Korean Journal of Medicinal Crop Science
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    • v.26 no.5
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    • pp.391-400
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    • 2018
  • Background: Atractylodes radix is a well-known medicinal crop having many physiological effects. This study was conducted to select useful Atractylodes japonica ${\times}$ Atractylodes macrocephala (AJM) cultivars by comparing anti-oxidative and anti-inflammatory efficacies. Methods and Results: Seven extracts from AJM cultivars were used to treat lipopolysacchride (LPS)-treated BV2 cells, and the effects on cell viability and inhibition on reactive oxygen species (ROS) and nitric oxide (NO) production were analyzed. In vitro scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and peroxynitrite ($NOO^-$) radicals were also investigated. Contents of total phenol, atractylenolide I, and atractylenolide III in the AJM extracts were measured using high performance liquid chromatography (HPLC) or spectrophotometry. The experiments show that none of the seven extracts was cytotoxic above 89.2% at $20-250{\mu}g/m{\ell}$. Extracts of Gowon, Dawon, Sangchul, and Huchul inhibited ROS generation in a dose-dependent manner, and Sangchul extract showed the highest inhibition on ROS production. All the AJM extracts showed effective inhibitory activity after on NO release in the LPS-treated BV2 cells, and Sangchul extract showed the highest activity. Sangchul extract had the most potent scavenging activities for $NOO^-$ and had some DPPH radical scavenging effect. Sangchul extract also had the highest content at total phenol and atractylenolide I content. Atractylenolide III was not detected in the AJM extracts. Conclusions: The results suggested that Sangchul was the most useful anti-oxidative and anti-inflammatory resource among the AJM cultivars.

Effect of Coffee-like Green Tea Preparation on Cytotoxicity of Human Cancer and Normal Cells (Coffee-like green tea의 인체암세포 및 정상세포에 대한 독성)

  • Moon, Yean Guy;Kwon, Jung Min;Kim, Jong Cheol;Park, Han Min;Cho, Yong Un;Jung, Kwan Ju;Ha, Yeong Lea
    • Journal of Life Science
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    • v.23 no.1
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    • pp.84-94
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    • 2013
  • The cytotoxicity of coffee-like green tea (CLGT) was determined in a human breast cancer cell line, MCF-7; a human prostate cancer cell clone, PC-3; a human neuroblastoma cell line, SK-N-SH; and a rat cardiomyoblast cell line, H9c2, with reference to green tea leaves (GTL). The CLGT was prepared by roasting the GTL for 60 min at $240^{\circ}C$ in a temperature-controlled frying pan. The CLGT preparation imitated the flavor and taste characteristics of coffee fairly well according to sensory analysis. The CLGT preparation had no adverse cytotoxic effects on the cancer cells or the normal cells compared to GTL. No significant change in the antioxidant activity was seen in the CLGT preparation compared to that of GTL. The amount of total protein, sugar, and phenolic compounds was reduced in the preparation relative to those in GTL, a fact that might explain the coffee-like flavor and/or taste characteristics of the CLGT preparation. These results suggest that CLGT prepared by roasting GTL for 60 min at $240^{\circ}C$ does not show any adverse effects on cancer cells and normal cells compared to GTL. They imply that CLGT could be safe for human consumption.

Growth Inhibitory Effect of Extracts of Propolis on Epithelial Ovarian Cancer Cells (상피성 난소암 세포에서 프로폴리스 추출물의 세포 증식 저해 효과)

  • Yang, Ga Ram;Yoon, Kyung Mi;Oh, Hyun Ho;Kim, Min Sung;Hwang, Tae Ho;An, Won Gun
    • Journal of Life Science
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    • v.27 no.7
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    • pp.834-839
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    • 2017
  • Propolis is a natural product collected from plants by honey bees product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anti-cancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. Ovarian cancer is the second most common newly diagnosed cancer from all cancers among women in Korea and the leading cause of death from gynecological malignancies. While most ovarian cancer patients initially respond to surgical debulking and chemotherapy, patients later succumb to the disease. Thus, there is an urgent need to test novel therapeutic agents to counteract the high mortality rate associated with ovarian cancer. In this study, we investigated the anti-cancer properties and the active mechanism of Australian propolis in human epithelial ovarian cancer A2780 cells. Our data revealed that propolis showed a cytotoxic activity in a dose-dependent manner. Flow cytometric analysis for cell cycle arrest and apoptosis using propidium iodide staning and annexin V-FITC indicated that propolis could induce cycle arrest in the G0/G1 phase and apoptosis in a dose-dependent manner on human epithelial ovarian cancer cells. These results suggest that the Australian propolis is potential alternative agent on ovarian cancer prevention and treatment.

Induction of Apoptotic Cell Death by Aqueous Extract of Cordyceps militaris Through Activation of Caspase-3 in Human Hepatocarcinoma Hep3B Cells (Hep3B 간암세포에서 Caspase-3 활성화를 통한 동충하초 열수추출물의 Apoptosis 유도에 관한 연구)

  • Kim, Kyung-Mi;Park, Cheol;Seo, Sang-Ho;Hong, Sang-Hoon;Lee, Won-Ho;Choi, Yung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.6
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    • pp.714-720
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    • 2008
  • Cordyceps militaris is a medicinal fungus which has been used for patient suffering from cancer in Oriental medicine. It was previously reported that C. militaris extracts are capable of inhibiting tumor growth and inducing apoptosis; however, the anti-poliferative effects of human cancer cells have been poorly understood. In this study, to elucidate the anti-cancer mechanisms of human cancer cells by treatment with aqueous extract of C. militaris (AECM), we investigated the anti-proliferative effects of AECM in human hepatocarcinoma Hep3B cells. AECM treatment inhibited the growth of Hep3B cells and induced the apoptotic cell death in a concentration-dependent manner such as formation of apoptotic bodies and increased populations of apoptotic-sub G1 phase. The induction of apoptosis by AECM was connected with a proteolytic activation of caspase-3 and caspase-8. and concomitant degradation of poly (ADP-ribose) polymerase (PARP) and ${\beta}$-catenin proteins. Furthermore, caspase-3 inhibitor, z-DEVD-fmk, significantly inhibited AECM-induced apoptosis demonstrating the important role of caspase-3 in the bserved cytotoxic effect. Taken together, these findings suggest that AECM-induced inhibition of human hepatocarcinoma cell proliferation is associated with the induction of apoptotic cell death via activation of caspase-3 and C. militaris may have therapeutic potential in human cancer.

Effects of Rhodiola Rosea on Brain Edema and Matrix Metalloproteinase Expressions Following Intracerebral Hemorrhage in the Rat (홍경천(紅景天)이 뇌조직내출혈(腦組織內出血) 흰쥐의 뇌부종(腦浮腫)과 Matrix Metalloproteinase 발현에 미치는 영향)

  • Ryu, Sa-Hyun;Lee, Joon-Suk;Shin, Jung-Won;Kim, Seong-Joon;Sohn, Nak-Won
    • The Korea Journal of Herbology
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    • v.26 no.4
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    • pp.169-180
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    • 2011
  • Objectives : This study aimed at evaluation of the effects of Rhodiola rosea on brain edema and expressions of matrix metalloproteinases (MMPs) related to blood-brain barrier (BBB) disruption. Methods : Brain edema following intracerebral hemorrhage (ICH) was induced by the stereotaxic intrastriatal injection of bacterial collagenase type VII in rats (Sprague-Dawley). Then ethanol extract of Rhodiola rosea was treated once a day for 3 days. Brain edema % and water contents, and BBB leakage were examined. Immunohistochemistry was processed for MMP-9, MMP-12, and iNOS expressions in the brain sections and each immuno-labeled cells were analyzed with image analysis software. Results : 1. Ethanol extract of Rhodiola rosea reduced brain edema following ICH in rats significantly. 2. Ethanol extract of Rhodiola rosea reduced excessive brain tissue water contents following ICH in rats significantly. 3. Ethanol extract of Rhodiola rosea reduced BBB leakage in the cerebral cortex following ICH in rats. 4. Ethanol extract of Rhodiola rosea reduced cellular edema of neurons in peri-hematoma and the cerebral cortex following ICH in rats significantly. 5. Ethanol extract of Rhodiola rosea reduced MMP-9 positive cells in the cerebral cortex following ICH in rats significantly. 6. Ethanol extract of Rhodiola rosea reduced MMP-12 positive vessels in the cerebral cortex following ICH in rats significantly. 7. Ethanol extract of Rhodiola rosea reduced iNOS positive cells in the cerebral cortex and external capsule following ICH in rats significantly. Conclusions : These results suggest that Rhodiola rosea reveals protective effect against brain edema and cytotoxic edema of neurons by means of down-regulation of MMPs and iNOS expressions, and inhibition of BBB leakage.

Antitumor and Immuno-modulatory Effect Against Mouse Sarcoma 180 of Crude Polysaccharides Extracted from Fruiting Body of Armillaria tabescens (뽕나무버섯부치(Armillaris tabescens)의 자실체에서 추출한 조다당류의 생쥐 Sarcoma 180에 대한 항암 및 면역증강 효과)

  • Lee, Geon-Woo;Kim, Hye-Young;Lee, U-Youn;Lee, Tae-Soo
    • The Korean Journal of Mycology
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    • v.35 no.2
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    • pp.101-108
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    • 2007
  • Armillaria tabescens, one of edible and medicinal mushrooms belonging to Agaricales of Basidiomycota, has been known to have outstanding curative effects on chronic hepatitis and cholecystitis and inhibitory effects on the sarcoma 180 and Erhrlich carcinoma of mice. Neutral saline soluble (0.9% NaCl), hot water soluble and methanol soluble substances (hereinafter referred to Fr, NaCl, Fr. HW and Fr, MeOH, respectively) were extracted from fruiting body of the mushroom. In vitro cytotoxicity tests showed that crude polysaccharides were not cytotoxic against cancer cell lines such as NIH3T3 and Sarcoma 180 at the concentration of $2000\;{\mu}g/ml$. Intraperitoneal injection with crude polysaccharides exhibited life prolongation effect of $28.8{\sim}46.5%$ in mice inoculated with Sarcoma 180, respectively. Fr. NaCl improved the immunopotentiation activity of B lymphocyte by increasing the alkaline phosphatase activity by $1.8{\sim}2.1$ folds, respectively. In case of Fr, NaCl, the numbers of peritoneal exudate cells and circulating leukocytes were increased by 9 and 1.9 folds, respectively.

Studies on Immuno-Modulatory and Antitumor Effects of Crude Polysaccharides Extracted from Fruiting Body of Oudemansiella radicata (민긴뿌리버섯(Oudemansiella radicata)의 자실체로부터 추출한 조다당류의 항암 및 면역 활성 효과에 관한 연구)

  • Kim, Sang-Beom;Lee, Geon-Woo;Lee, U-Youn;Lee, Tae-Soo
    • The Korean Journal of Mycology
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    • v.35 no.2
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    • pp.109-114
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    • 2007
  • Oudemansiella radicata, edible and medicinal mushroom belonging to Agaricales of Basidiomycota, has been known to exhibit outstanding curative effects on the fungal infection and hypertension caused by high blood pressure. Neutral saline soluble (0.9% NaCl), hot water soluble and methanol soluble substances (hereinafter referred to Fr, NaCl, Fr. HW and Fr. MeOH, respectively) were extracted from fruiting body of the mushroom. In vitro cytotoxicity test showed that Fr. NaCl was not cytotoxic against NIH3T3 and Sarcoma 180 at the concentration of $10{\sim}1,000\;{\mu}g/ml$. Intraperitoneal injection with Fr. NaCl exhibited antitumor activity with life prolongation effect of $42.9{\sim}66.7%$ in mice inoculated with Sarcoma 180. Fr. NaCl improved the immunopotentiating activity of B lymphocyte by increasing the alkaline phosphatase activity by $1.4{\sim}3$ folds compared with controlled and LPS groups, respectively. Intraperitoneal injection with Fr. MeOH increased the numbers of peritoneal exudate cells and circulating leukocytes by 3.5 and 2.5 folds, respectively. Therefore, the antitumor effect exhibited on mouse Sarcoma 180 cells was likely due to immune-modulating activity of crude polysaccharides extracted from fruiting body of O. radicata.

Inflammatory mediator regulation of the Zizyphus jujube leaf fractions in the LPS-stimulated Raw264.7 mouse machrophage (LPS로 염증이 유도된 Raw 264.7 대식세포에서 대추(Zizyphus jujube) 잎 분획물의 염증매개물질 억제)

  • Kim, Ye Jin;Son, Dae-Yeul
    • Food Science and Preservation
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    • v.21 no.1
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    • pp.114-120
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    • 2014
  • Zizyphus jujube leaf fractions (ZLFs) showed no cytotoxic effects of up to $100{\mu}g/mL$, while the anti-inflammatory effects of ZLFs were analyzed by checking the productions of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), cyclooxygenase-2 (COX-2), and inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 in the lipopolysaccharide (LPS)-stimulated Raw264.7 macrophage up to the concentration of $100{\mu}g/mL$. ZLFs ($100{\mu}g/mL$) demonstrated a strong anti-inflammatory activity that reduced 61~85% of NO and 71~100% of $PGE_2$ production in the LPS-stimulated Raw264.7 macrophage. Even the low ZLFs concentration of $1{\mu}g/mL$ have reduced NO and $PGE_2$ production by 34~64%. Expressions of COX-2 protein were also effectively inhibited by the ZLFs. Furthermore, the TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 production were significantly suppressed through the treatment of ZLFs at concentrations of 1, 10, and $100{\mu}g/mL$. In the order of the Zizyphus jujube leaf water fraction (ZLWF) < buthanol fraction (ZLBF) < ethyl acetate fraction (ZLEF) showed anti-inflammatory activity. In particular, the ethyl acetate fraction ZLEF at $100{\mu}g/mL$ showed an excellent anti-inflammatory activity by reducing the production of NO, $PGE_2$, COX-2, and inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6) in the level of Raw264.7 macrophage without LPS-stimulation or even better. The results of our study suggest the potential of ZLEF for use as an excellent ant-inflammatory inhibiting mediator and may be used as a therapeutic approach to various inflammatory diseases.