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Effect Naetakchungumsankamibang on Skin tumor induced by 3-MCA and Immunological Response (內托千金散加味方이 3-MCA로 誘發된 皮膚癌 및 免疫調節作用에 미치는 影響)

  • Kim, Hee-taek;Roh, Seok-seon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.12 no.2
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    • pp.20-52
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    • 1999
  • In order to investigate the effect of Naetakchungumsankamibang(NTCGS) water extract on the skin tumor induced by 3-MCA and immunological responses in mice, the cytotoxicity against SK-MEL-2 cells and total number of tumors induced by 3-MCA were measured. The numbers of WBC, platelets and RBC, plaque forming cells, hemagglutinin titer, hemolysis titer, carbon clearance, proliferation of splenocyte by thymidine uptake assay, splenic leukocyte by FACS analysis and $TNF-{\alpha}$ were also measured for the evaluation of the immunological responses. The results were obtained as follows: 1. In cytotoxicity against SK-MEL-2 cells, concentration inhibiting cell growth up to below $20\%$ of control was recognized at 1mg/ml of NTCGS. 2. In Inhibitory effect on the skin tumor induced by 3-MCA, the results showed a strong inhibitory effect of NTCGS. 3. In hematological changes in the tumor bearing mice, the numbers of WBC decreased significantly in NTCGS treated group as compared with control. 4. In hematological changes in the tumor bearing mice, the numbers of platelets increased significantly in NTCGS treated group as compared with control. 5. In hematological changes in the tumor bearing mice, the numbers of RBC increased with no significance in NTCGS treated group as compared with control. 6. Effects of the plaque forming cells in the tumor bearing mice, NTCGS treated group exhibited a significant effect compared with control. 7. In terms of the effects on hemagglutinin titer, NTCGS treated group showed higher level than control, without significance. 8. In terms of the effects on hemolysis titer, NTCGS treated group showed higher level than control, without significance. 9. In terms of the effects on phagocytic index K in Balb/C mice, NTCGS treated group showed significant difference from control. 10. In terms of the effects on proliferation of splenocyte by thymidine uptake assay, NTCGS showed significant effect at the concentration of 0.5mg/ml. 11. In terms of the effects on splenic leukocyte of Balb/C mice by FACS analysis, NTCGS treated group showed significantly higher level of helper T cell, B cell and macrophage than in control. 12. In terms of the effects on the secretion of $TNF-{\alpha}$, the treated group showed significant effect at the concentration of 1mg/ml of NTCGS. Based on the results summarized above, NTCGS is considered to have antitumor activity and immunological responses against skin tumor, and to be usable fur the treatment.

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Da-125 a New Antitumor Agent, Inhibits Topoisomerase II as Topoisomerase Poison and DNA Intercalator Simultaneously

  • Seo, Jin-Wook;Lee, Hak-Sung;Lee, Min-Jun;Kim, Mi-Ra;Shin, Cha-Gyun
    • Archives of Pharmacal Research
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    • v.27 no.1
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    • pp.77-82
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    • 2004
  • DA-125, a novel derivative of adriamycin, is known for its anti-cancer activity. In this study, the inhibitory mechanism of DA-125 on topoisomerase was investigated in the simian virus 40 (SV40) replicating CV-1 cell by studying the SV40 DNA replication intermediates and DNA-topoisomerase complexes. DNA-protein complexes that were formed in the drug-treated cells were quantitated by using a glass filter assay. SV40 DNA replication intermediates that were accumulated in the drug-treated CV-1 cell were analyzed in a high resolution gel. DA-125 did not accumulate B-dimers of SV40 DNA replication intermediates which were found in the adriamycin-treated CV-1 cells. DA-125 induced a dose-dependent formation of the DNA-protein complexes, while adriamycin did not. When adriamycin and etoposide (VP16) were added to the SV40-infected cells at the same time, adriamycin blocked the formation of the DNA-protein complexes induced by VP16 in a dose-dependent manner. However, DA-125 blocked the formation of the DNA-protein complexes induced by VP16 up to the maximum level of the DNA-protein complexes that were induced by DA-125 alone. Adriamycin and DA-125 did not inhibit the formation of the DNA-protein complexes that were caused by camptothecin, a known topoisomerase I poison. DA-125 is bifunctional in inhibiting topoisomerase II because it simultaneously has the properties of the topoisomerase II poison and the DNA intercalator. As a topoisomerase II poison, DA-125 alone induced dose-dependent formation of the DNA-protein complexes. However, as a DNA intercalator, it quantitatively inhibited the formation of the DNA-protein complexes induced by a strong topoisomerase II poison VP16. Furthermore considering that the levels of the DNA-protein complex induced by VP16 were decreased by DA-125 in terms of the topoisomerase II poison, we suggest that DA-125 has a higher affinity to the drug-binding sites of DNA than VP16 has.

Schisandrae Fructus ethanol extract attenuates particulate matter 2.5-induced inflammatory and oxidative responses by blocking the activation of the ROS-dependent NF-κB signaling pathway

  • Lee, Hyesook;Park, Cheol;Kwon, Da Hye;Hwangbo, Hyun;Kim, So Young;Kim, Min Yeong;Ji, Seon Yeong;Kim, Da Hye;Jeong, Jin-Woo;Kim, Gi-Young;Hwang, Hye-Jin;Choi, Yung Hyun
    • Nutrition Research and Practice
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    • v.15 no.6
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    • pp.686-702
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    • 2021
  • BACKGROUND/OBJECTIVES: Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages. MATERIALS/METHODS: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E2 (PGE2), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model. RESULTS: The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae. CONCLUSIONS: Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage.

Beyond the Molecular Facilitator, CD82: Roles in Metastasis Suppressor, Stem Cell Niche, Muscle Regeneration, and Angiogenesis (분자 촉진제를 넘어, CD82: 전이억제자, 줄기세포 니쉬, 근육 재생 및 혈관신생에서의 역할)

  • Lee, Hyun-Chae;Han, Jung-Hwa;Hur, Jin
    • Journal of Life Science
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    • v.31 no.9
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    • pp.856-861
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    • 2021
  • CD82/KAI1, identified as a metastasis suppressor, was initially known only as a molecular facilitator, but its various functions have recently been revealed. CD82 plays an important role in the stem-progenitor cell, angiogenesis, and muscle. We would like to introduce the recently reported functions and roles of CD82 in this review. CD82 is a member of the tetraspanin family, which consists of four transmembrane domains. The interaction between CD82 and cell adhesion molecules suppresses the metastasis of cancer. CD82 regulates the cell cycle of stem-progenitor cells in the stem cell niche. In the bone marrow, CD82 is expressed on long-term repopulating hematopoietic stem cells (LT-HSCs), which show multipotent differentiation potential. The interaction between CD82 and Duffy antigen receptor for chemokines (DARC) induces quiescence in LT-HSCs. CD82 also regulates Rac1 activity, resulting in the homing and engraftment of HSCs into the bone marrow niche. Besides, CD82 maintains the differentiation potential of muscle stem cells and prevents angiogenesis by inhibiting the expression of cytokines, such as IL-6 and VEGF and adhesion molecules in endothelial cells. CD82 is a key membrane protein that distinguishes the hierarchy of stem-progenitor cells, and is also important for amplification and verification of cellular resources. Further studies on the function of CD82 in various organs and cells are expected to advance cell biology and cell therapy.

Exploration of Duty System and Needs Assessment in Lifelong Learning Counseling Practice (평생교육 담당자의 평생학습상담 직무 탐색 및 요구도 분석)

  • Jo, Eun-San;Yun, Myung-Hee;Ku, Kyung-Hee
    • Journal of vocational education research
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    • v.35 no.6
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    • pp.65-84
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    • 2016
  • This study aims to explore the duty system of the lifelong learning counseling, and to analyze the needs of counseling practice which are conceived by lifelong education practitioners. Based on the related prior studies, the duty system of lifelong learning counseling was investigated and classified. Also, differences of how to recognize the importance of counseling job and how to practice counseling are assessed by Borich method. After data were collected by practitioners from lifelong education field, the dependent t-test and the Borich needs assessment formula were used for analysis of the collected data. The results are as follows: the 4 subdivided duties of lifelong learning counseling are formation of relationship, learner's analysis, learning promotion, and follow-up management. The 11 tasks are learner's interview, providing learning information, analysis of learner's characteristics and needs, learning level diagnosis, diagnosis of learning inhibiting factors, promotion of learning motivation, advice of learning course and learning method, support of study circle activity, career planning counseling, follow-up counseling, and counseling evaluation. According to the needs assessment, learner's analysis is conceived as the most important duty among the 4 sub-duties, and learner's analysis is regarded as second important duty by the counseling practitioners. Among the 11 tasks, providing learning information is the most important tasks among counseling practitioners, and analysis of learner's characteristics and needs is followed as second task. The duty system of the lifelong learning counseling and needs assessment data can be used as the basic data for lifelong education practitioners to conduct the duty of lifelong learning counseling efficiently and to support the lifelong learning plan according to learner's characteristics.

Whitening Activities of Ethanol Extract from Polygonum amphibium L. (물여뀌 에탄올 추출물의 미백 효과)

  • Hwang, Buyng Su;Lee, Seung Young;Kang, Chang Hee;Han, Woog;Oh, Young Taek;Yu, Sang Mi;Kim, Min Jin;Kim, Chul Hwan;Eom, Jung Hye;Jeong, Sang Chul;Lee, Wook Jae;Ahn, Young Hee;Jeong, Yong Tae
    • Microbiology and Biotechnology Letters
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    • v.47 no.2
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    • pp.195-200
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    • 2019
  • The purpose of this study was to investigate the melanogenesis inhibiting activity of the ethanol extract from Polygonum amphibium L. Firstly, the n-hexane (Hx), chloroform ($CHCl_3$), ethyl acetate (EA), n-butanol (BuOH), and water (Water) fractions were isolated from the P. amphibium L. ethanol extract. The efficacy of melanogenesis was found to significantly decrease via the EA and BuOH fractions when compared to the control in B16F10 cells. EA particularly showed the lowest melanin content in B16F10 cells when compared to all the other extracts. Concentration-dependent inhibition of melanin synthesis was also observed in the EA fraction at concentrations below $50{\mu}g/ml$, which did not exhibit cytotoxicity in B16F10 cells. Notably, the expression of three key proteins (tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2), which are involved in melanogenesis, were significantly decreased via the EA fraction. EA also inhibited body pigmentation in vivo in a zebrafish model. Overall, we demonstrated melanogenesis suppression using the EA fraction from P. amphibium L., which could be a potential candidate for an antimelanogenesis agent.

Antioxidant and Antimelanogenic Effects of Stevia rebaudiana Flower Extract

  • So, Gyeongseop;Lee, Sung Ryul;Kim, Sung Hyeok;Ha, Chang Woo;Park, Yuna;Jang, Sohee;Bak, Jong Phil;Koo, Hyun Jung;Sohn, Eun-Hwa
    • Korean Journal of Plant Resources
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    • v.32 no.3
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    • pp.220-227
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    • 2019
  • Stevia rebaudiana (Asteraceae), a perennial plant, has been used as a low-calorie sweetener and is being developed as a therapeutic agent for diabetes, hypertension, myocardial diseases, and microbial infections. Despite the common use of its leaves and stem, the bioavailability of the components present in S. rebaudiana flowers, when used as ingredients of cosmetics, has not been well investigated. Herein, we investigated the antioxidative and antimelanogenic effects of an aqueous extract of S. rebaudiana flowers (Stevia-F). Total flavonoid and phenolic content in Stevia-F were determined to be $8.64{\pm}0.23mg$ of quercetin equivalents/100 g and $631.5{\pm}2.01mg$ of gallic acid equivalents/100 g, respectively. The $IC_{50}$ values of Stevia-F for reducing power, and 2,2-diphenyl-1-picryl-hydrazyl-hydrate radical, hydrogen peroxide, and nitric oxide scavenging activities were 5541.96, 131.39, 466.34, and $10.44{\mu}g/mL$, respectively. Stevia-F showed inhibitory effects on the tyrosinase ($IC_{50}=134.74{\mu}g/mL$) and ${\alpha}$-glucosidase ($IC_{50}=114.81{\mu}g/mL$) activities. No significant cytotoxicity of Stevia-F was observed in B16F10 cells, treated with up to $100{\mu}g/mL$ of the extract for 24 and 48 h (p > 0.05). Stevia-F ($1-100{\mu}g/mL$) suppressed ${\alpha}$-melanocyte stimulating hormone-induced melanin production in B16F10 cells (p < 0.05) and also inhibited the cellular tyrosinase activity (p < 0.05). Overall, our results show that Stevia-F possesses potential for inhibiting tyrosinase and ${\alpha}$-glucosidase activities and has significant antioxidant capacity. The antimelanogenic potential of Stevia-F should extend the usage of S. rebaudiana flowers in the development of skin-whitening products.

Arg-Leu-Tyr-Glu Suppresses Retinal Endothelial Permeability and Choroidal Neovascularization by Inhibiting the VEGF Receptor 2 Signaling Pathway

  • Park, Wonjin;Baek, Yi-Yong;Kim, Joohwan;Jo, Dong Hyun;Choi, Seunghwan;Kim, Jin Hyoung;Kim, Taesam;Kim, Suji;Park, Minsik;Kim, Ji Yoon;Won, Moo-Ho;Ha, Kwon-Soo;Kim, Jeong Hun;Kwon, Young-Guen;Kim, Young-Myeong
    • Biomolecules & Therapeutics
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    • v.27 no.5
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    • pp.474-483
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    • 2019
  • Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, ${\beta}$-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.

Growth of Candida albicans Biofilm is Inhibited by Salvia miltiorrhiza (단삼에 의한 Candida albicans 바이오필름 발달의 억제)

  • Lee, Heung-Shick;Kim, Younhee
    • Microbiology and Biotechnology Letters
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    • v.47 no.3
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    • pp.465-472
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    • 2019
  • Candida albicans is an opportunistic human pathogen that causes infections. Candidiasis is often related to antifungal resistance because the pathogen has the ability to form biofilms. In a previous study, we found that the Salvia miltiorriza ethanol extract demonstrated anticandidal activity by altering membrane permeability and inhibiting the cell wall synthesis in C. albicans. Our results here demonstrate that $78{\mu}g/ml$ of the S. miltiorriza extract significantly diminished the early stage biofilms formed by 10 clinical C. albicans isolates by 51.3%; this was analyzed by 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT) reduction assay. The effect of the S. miltiorrhiza extract on the adhesion of C. albicans cells to polystyrene plates and germ tube formation was examined via microscopic investigation. Although the density of the adhered cells was remarkably reduced up on incubation with $39{\mu}g/ml$ S. miltiorrhiza extract, germ tube formation by C. albicans was rarely affected. Quantitative real-time PCR analysis showed that the S. miltiorrhiza extract downregulated the expression of C. albicans hypha-specific genes, EAP1 by 34.7% (p < 0.001), ALS1 by 45.0% (p < 0.001), ALS3 by 48.1% (p < 0.001), and ECE1 by 21.3% (p = 0.006), respectively. Our data suggest that the S. miltiorrhiza ethanol extract significantly inhibited the early stage of biofilm formation by C. albicans by interfering with cell adhesion, by downregulating EAP1, ALS1 and ALS3, and presumably by modifying the cell wall and membrane structure.

Cudrania tricuspidata Fruit Extract Ameliorates Free Fatty Acid-induced Lipid Accumulation in HepG2 Cells (유리지방산으로 지방축적을 유도한 HepG2 cells 대한 꾸지뽕 열매 추출물의 개선 효과)

  • Lee, Hyo-Jeong;Park, Se-Eun;Kim, Seung
    • Journal of Life Science
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    • v.29 no.10
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    • pp.1144-1151
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    • 2019
  • Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with various metabolic syndromes, such as obesity, dyslipidemia, hypertension, and diabetes. Cudrania tricuspidata is a medicinal plant distributed widely in Asia and has been used in clinical practice to treat various diseases. The aim of this study is to determine the lipid-lowering effects of C. tricuspidata fruit extract (CTE) using a cell model induced by free fatty acids (FFAs). HepG2 cells were exposed to 1mM FFAs (palmitic acid:oleic acid = 2:1) for 24 hr to simulate the conditions of NAFLD in vitro. CTE attenuated the increases of lipid accumulation, intracellular triglyceride, and cholesterol content and inhibited 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) activity in the HepG2 cells in a dose-dependent manner. Also, CTE inhibited the protein expression of lipogenesis-related genes, such as sterol regulatory element-binding protein-1/-2 (SREBP-1/-2), fatty acid synthase (FAS), and stearoyl CoA desaturase-1 (SCD-1) in FFAs-induced lipid accumulation in HepG2 cells. In addition, CTE-induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in HepG2 cells. These results suggest that CTE attenuates hepatic lipid accumulation by inhibiting lipogenesis through the modulation of the AMPK signaling pathway on FFAs-induced lipogenesis in HepG2 cells and may potentially prevent NAFLD.