• Title/Summary/Keyword: leading compound

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Resveratrol Suppresses CD4+ T Cell Activation and Differentiation in vitro (Resveratrol의 CD4+ T 세포 활성과 분화 억제 효과)

  • Seo, Dong-Won;Yi, Young-Joo;Lee, Sang-Myeong
    • Korean Journal of Plant Resources
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    • v.27 no.5
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    • pp.567-575
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    • 2014
  • Resveratrol is a naturally occurring stilbene which is safe and well-described compound with a potent anti-inflammatory activity. Recent studies suggested that resveratrol suppressed various inflammation mediated diseases such as asthma, chronic colitis, rheumatoid arthritis, and type 1 diabetes. These studies indicated that resveratrol might directly modulate $CD4^+$ helper T cells (Th cells)-mediated immune responses. However, it is not fully elucidated whether resveratrol directly regulates $CD4^+$ Th cell activation and differentiation. In the present study, $CD4^+$ Th cells were purified from C57BL/6 and treated with various concentrations of resveratrol. We found that resveratrol directly suppressed $CD4^+$ Th cells activation, leading to a defect in T cell proliferation. When $CD4^+$ Th cells were treated with resveratrol, cytokine production was also significantly reduced in a dose dependent manner. In accordance with these results, resveratrol even inhibited $CD4^+$ Th cells differentiation into Th1, Th2 or Th17, which produces IFN-${\gamma}$, IL-4 or IL-17 respectively. We also found that resveratrol could induce apoptosis of $CD4^+$ T cells at a high concentration. Our data demonstrated that resveratrol inhibited directly $CD4^+$ Th cells activation and differentiation. It suggests that resveratrol could be an efficient therapeutic strategy for autoimmune diseases in which $CD4^+$ Th cells play a critical role.

Survey on Compliance of Pesticide Registration Standard and Pesticide Usage of Paddy Rice and Leaf Vegetables in Korea (농약등록기준 준수 현황과 수도 및 엽채소류 사용량 조사)

  • Kim, Kyung-Sun;Kim, Kang-Ho;Kim, Nam-Suk;Ihm, Yang-Bin;Lee, Hee-Dong;Kim, Hyu-Gyung;You, Oh-Jong;Oh, Byung-Youl;Im, Geon-Jae;Ryu, Gab-Hee
    • The Korean Journal of Pesticide Science
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    • v.10 no.3
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    • pp.183-188
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    • 2006
  • A nation-wide monitoring survey was performed to look into pesticide use pattern and amount on farmers' field after the national registration of pesticides from 2003 to 2004. Tow hundred ninety two leading farmers involved in the survey were chosen from main cultivating regions of targeted crops in consideration with area. Most farmers involved in the survey follow the safe use guideline of pesticides, while their information to select and making-decision for purchasing pesticides were done according to the recommendation of mainly pesticide market dealers or agricultural cooperative dealers. Used amount of pesticide per unit cropping area was surveyed as 5.51 on paddy, 3.91 on field cabbage, 2.93 on greenhouse cabbage, 0.76 on lettuce, 0.55 on spinach, 1.34 on perilla leaf, 4.89 on leek and 0.42 kg $ha^{-1}$ on young radish. As compound with those surveyed from 1999 to 2000, the pesticide amounts used for rice, lettuce and perilla leaf were reduced while that for cabbage was increased.

Identification of a Neolignan Glycoside from the Pine Tree, Pinus densiflora Showed Antithrombotic Activity (Pinus densiflora 유래의 항트롬빈 활성을 나타내는 Neolignan Glycoside의 동정)

  • Seo, Min-Jeong;Kang, Byoung-Won;Jeong, Yong-Kee
    • Journal of Life Science
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    • v.24 no.8
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    • pp.873-879
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    • 2014
  • The constituents from the needles of the pine tree, Pinus densiflora, were purified and investigated for antithrombotic activity. The needles were initially extracted three times with 70% ethanol, and the extract was sequentially fractionated with chloroform and n-butanol. The aqueous layer formed after n-butanol fractionation was subjected to purification by medium pressure and high pressure liquid chromatography. The two neolignans, 2, 3-dihydro-7-hydroxyl-3-hydroxymethyl-2-(4'-hydroxyl -3-methoxyphenyl)-5-benzofuranpropanol-3-O-${\alpha}$-rhamnopyranoside (a neolignan glycoside) and 2, 3-dihyro-3-hydroxymethyl-7-methoxy-2-(4'-hydroxyphenyl-3'-methoxy)-5-benxofuran propanol 4'-O-${\alpha}$-rhamnopyranoside (icariside $E_4$) were identified by $^1H$ and $^{13}C$ NMR spectra. The effect of the purified compounds, the neolignan glycoside and icariside $E_4$ on thrombin inhibition were investigated by measuring thrombin clotting time in plasma. As a result, the clotting of the neolignan glycoside was delayed four times compared to that of icariside $E_4$. In addition, an analysis of the inhibition effect by changing the concentration showed that the clotting time was delayed in accordance with an increase in the concentration of the neolignan glycoside. Furthermore, we examined the interaction of thrombin and fibrinogen to clarify the action mechanism. As a result, the delay of clotting time in the response of thrombin and pure fibrinogen may indicate that neolignan glycosides inhibit the thrombin action in a direct manner, leading to the suppression of fibrin generation.

A Novel Pyruvate Kinase M2 Activator Compound that Suppresses Lung Cancer Cell Viability under Hypoxia

  • Kim, Dong Joon;Park, Young Soo;Kim, Nam Doo;Min, Sang Hyun;You, Yeon-Mi;Jung, Yuri;Koo, Han;Noh, Hanmi;Kim, Jung-Ae;Park, Kyung Chan;Yeom, Young Il
    • Molecules and Cells
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    • v.38 no.4
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    • pp.373-379
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    • 2015
  • Pyruvate kinase M2 isoform (PKM2), a rate-limiting enzyme in the final step of glycolysis, is known to be associated with the metabolic rewiring of cancer cells, and considered an important cancer therapeutic target. Herein, we report a novel PKM2 activator, PA-12, which was identified via the molecular docking-based virtual screening. We demonstrate that PA-12 stimulates the pyruvate kinase activity of recombinant PKM2 in vitro, with a half-maximal activity concentration of $4.92{\mu}M$, and effectively suppresses both anchorage-dependent and -independent growth of lung cancer cells in non-essential amino acid-depleted medium. In addition, PA-12 blocked the nuclear translocalization of PKM2 in lung cancer cells, resulting in the inhibition of hypoxia response element (HRE)-mediated reporter activity as well as hypoxia-inducible factor 1 (HIF-1) target gene expression, eventually leading to the suppression of cell viability under hypoxia. We also verified that the effects of PA-12 were dependent on PKM2 expression in cancer cells, demonstrating the specificity of PA-12 for PKM2 protein. Taken together, our data suggest that PA-12 is a novel and potent PKM2 activator that has therapeutic implications for lung cancer.

Immunosuppressive Activity of Cultured Broth of Entompathogenic Bacteria on the Beet Armyworm, Spodoptera exigua, and Their Mixture Effects with Bt Biopesticide on Insecticidal Pathogencity (파밤나방(Spodoptera exigua)에 대한 곤충병원세균류 배양액의 곤충면역억제활성 및 비티 생물농약과 혼합효과)

  • Kim, Jea-Min;Nalini, Madanagopal;Kim, Yong-Gyun
    • The Korean Journal of Pesticide Science
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    • v.12 no.2
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    • pp.184-191
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    • 2008
  • Entomopathogenic bacteria (Xenorhabdus nematophila, X. sp. and Photorhabdus temperata subsp. temperata) isolated from entomopathogenic nematodes express potent insecticidal activity in insect hemocoel. They are also known to suppress insect immune mediation by inhibiting phospholipase $A_2$, leading to host immunosuppression. This study analyzed effects of their cultured broths on inhibiting insect immunosuppression. For this, we removed all bacterial cells using $0.2\;{\mu}m$ pore sized membrane from the bacteria-cultured broth. All three sterilized cultured media, in dose-dependent manners, significantly inhibited hemocyte-spreading behavior of 5th instar larvae of Spodoptera exigua. However, they showed differential inhibitory activities among different bacterial species, in which X. nematophila showed the most potent inhibitory activity. This immunosuppressive effect was applied to increase the pathogenicity of Bacillus thuringiensis (Bt). All three bacterial cultured broths including bacterial cells significantly potentiated Bt pathogenicity against young S. exigua larvae when each of them was orally administered in a mixture of low dose of Bt. Finally, we tested the effect of oral administration of the cultured media containing the immunosuppressive compound(s) secreted by the bacteria. The membrane-sterilized cultured broths were mixed with the low dose of Bt and then orally administered to the young S. exigua. Only the cultured medium of X. nematophila showed increase of Bt pathogenicity. These results indicated that the; cultured media of the three bacteria possessed immunosuppressive factor(s), which may act to potentiate Bt toxicity to young S. exigua larvae.

In vivo Pharmacokinetics, Activation of MAPK Signaling and Induction of Phase II/III Drug Metabolizing Enzymes/Transporters by Cancer Chemopreventive Compound BHA in the Mice

  • Hu, Rong;Shen, Guoxiang;Yerramilli, Usha Rao;Lin, Wen;Xu, Changjiang;Nair, Sujit;Kong, Ah-Ng Tony
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.911-920
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    • 2006
  • Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

Effects of FIN-TECH use motivation on User Attitude and Word Of Mouth Intention: Focus on a Innovation Resistance Tendency and Type of Message (Rational, Emotional) (핀테크 이용 동기에 따른 이용자 태도와 구전의도의 관계 - 혁신저항과 메시지 유형의 조절효과 -)

  • Seol, Sang-Cheol;Jung, Sung-Gwang;Choi, Woo-Young
    • Management & Information Systems Review
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    • v.36 no.5
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    • pp.195-222
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    • 2017
  • Today's economy is becoming more and more convergence between different industries as the demarcation of the boundaries of all areas is leading to innovations such as mobile and social network services. So Fin-tech is a new technology that can combine the advantages of mobile and Internet with the technology revolution to easily handle financial and IT tasks. This Fin-tech is a compound word of finance and technology. The purpose of this study is to investigate the overall structural relationship between Fin-Tech use motivation (usefulness, enjoyment) on user attitude and word of mouth intention. In addition, we investigated how FinTech use motivation, user attitude, and word of mouth intention change according to innovation resistance tendency. And, we examined how the motivation, user attitude, and word of mouth intention of FinTech change according to the message type (rational and emotional). The main results of this study are as follows. First, the usefulness and enjoyment of motivation for using FinTech have a positive effect on user attitude, and user attitude also has a positive effect on word of mouse intention. Second, the relationship between FinTech use motivation, user attitude, and word of mouth intention was found to difference according to consumers' innovation resistance. Third, it was found that the relationship between FinTech use motivation, user attitude, and word of mouth intention differs according to type of message (rational, emotional). At the conclusion of the study, the summary of the research results, implications and limitations, and future research direction are described.

Induction of Apoptotic Cell Death by Cordycepin, an Active Component of the Fungus Cordyceps militaris, in AGS Human Gastric Cancer Cells (동충하초 유래 cordycepin에 의한 AGS 인체 위암세포의 apoptosis 유발)

  • Lee, Hye Hyeon;Jeong, Jin-Woo;Choi, Yung Hyun
    • Journal of Life Science
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    • v.26 no.7
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    • pp.847-854
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    • 2016
  • Cordycepin, a derivative of the nucleoside adenosine, is one of the active components extracted from fungi of genus Cordyceps, and has been shown to have many pharmacological activities. In this study, we investigated the effects of cordycepin on proliferation and apoptosis of human gastric cancer AGS cells, and its possible mechanism of action. Treatment of cordycepin resulted in significant decrease in cell viability of AGS cells in a concentration-dependent manner. A concentration-dependent apoptotic cell death was also measured by agarose gel electrophoresis and flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled cordycepin treatment resulted in an enhanced expression of tumor necrosis factor-related apoptosis-inducing ligand, death receptor 5 and Fas ligand. Furthermore, up-regulation of pro-apoptotic Bax, and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL expression were also observed in cordycepin-treated AGS cells. These were followed by activation of caspases (caspase-9, -8 and -3), subsequently leading to poly (ADP-ribose) polymerase cleavage. Taken together, these findings indicate that cordycepin induces apoptosis in AGS cells through regulation of multiple apoptotic pathways, including death receptor and mitochondria. Although further mechanical studies are needed, our results revealed that cordycepin can be regarded as a new effective and chemopreventive compound for human gastric cancer treatment.

Protective effects of Acanthopanax koreanum Kakai extract against carbon tetrachloride-induced liver injury in Sprague-Dawley rats (사염화탄소로 유도된 간 손상에 대한 섬오갈피 추출물의 보호 효과)

  • Yang, Yoon Kyoung;Wang, Lin;Kwon, Oran
    • Journal of Nutrition and Health
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    • v.47 no.2
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    • pp.106-112
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    • 2014
  • Purpose: This study was conducted in order to investigate the protective effects of ethanolic extract of Acanthopanax koreanum Nakai (AE) against carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Methods: Male Sprague-Dawley rats were randomly divided into four groups in order to receive the following experimental diets with intraperitoneal injection of $CCl_4$ (2.0 mL/kg body weight, 20% solution 0.65 mL) for eight weeks (n = 8 per group): $CCl_4$ control (CON), $CCl_4$ + AE 1% (AE1), $CCl_4$ + AE 3% (AE3), or $CCl_4$ + acanthoic acid 0.037%, which is equivalent to AE 3% (AA). Results: Highest serum ALT activity and albumin level were observed in the $CCL_4$ control group, but showed a significant decrease by either AE or AA supplementation in a dose-dependent manner (p = 0.0063 and 0.0076, respectively). Both hemotoxylin and eosin staining and Masson's staining indicated remarkable prevention of $CCl_4$-induced liver damage in the AE3 group. $TNF{\alpha}$ and IL-6 production were significantly lowered in the AE treated groups, but not in the AA group (p = 0.0016 and p = 0.0002, respectively). The effects of AE3 were greater than those of AA for inflammation and liver toxicity biomarkers. Conclusion: Taken together, the results suggested that ethanolic extract of Acanthopanax koreanum Nakai provided hepatoprotective effects, leading to the reduction of inflammatory response. In addition, the effect of AE was superior to that of single compound AA.

Fermented ginseng, GBCK25, ameliorates steatosis and inflammation in nonalcoholic steatohepatitis model

  • Choi, Naeun;Kim, Jong Won;Jeong, Hyeneui;Shin, Dong Gue;Seo, Jeong Hun;Kim, Jong Hoon;Lim, Chae Woong;Han, Kang Min;Kim, Bumseok
    • Journal of Ginseng Research
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    • v.43 no.2
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    • pp.196-208
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    • 2019
  • Background: Nonalcoholic steatohepatitis (NASH) is one of the chronic inflammatory liver diseases and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The main purpose of this study was to clarify the effects of GBCK25 fermented by Saccharomyces servazzii GB-07 and pectinase, on NASH severity in mice. Methods: Six-wk-old male mice were fed either a normal diet (ND) or a Western diet (WD) for 12 wks to induce NASH. Each group was orally administered with vehicle or GBCK25 once daily at a dose of 10 mg/kg, 20 mg/kg, 100 mg/kg, 200 mg/kg, or 400 mg/kg during that time. The effects of GBCK25 on cellular damage and inflammation were determined by in vitro experiments. Results: Histopathologic analysis and hepatic/serum biochemical levels revealed that WD-fed mice showed severe steatosis and liver injury compared to ND-fed mice. Such lesions were significantly decreased in the livers of WD-fed mice with GBCK25 administration. Consistently, mRNA expression levels of NASH-related inflammatory-, fibrogenic-, and lipid metabolism-related genes were decreased in the livers of WD-fed mice administered with GBCK25 compared to WD-fed mice. Western blot analysis revealed decreased protein levels of cytochrome P450 2E1 (CYP2E1) with concomitantly reduced activation of c-Jun N-terminal kinase (JNK) in the livers of WD-fed mice administered with GBCK25. Also, decreased cellular damage and inflammation were observed in alpha mouse liver 12 (AML12) cells and RAW264.7 cells, respectively. Conclusion: Administration of GBCK25 ameliorates NASH severity through the modulation of CYP2E1 and its associated JNK-mediated cellular damage. GBCK25 could be a potentially effective prophylactic strategy to prevent metabolic diseases including NASH.