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Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway
( Yue Lu1 ),( Xian Li ),( Young Na Park ),( Okyun Kwon ),( Donggen Piao ),( Young Chae Chang ),( Cheorl Ho Kim ),( Eunkyung Lee ),( Jong Keun Son ),( Hyeun Wook Chang ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.3
The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of PGD2 and LTC4 in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase Cγ1 (PLCγ1)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c Jun NH2-terminal kinase and p38), and the nuclear factor-κB (NF-κB) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.
( Yue Lu ),( Seok Jong Suh ),( Choong Hwan Kwak ),( Kyung Min Kwon ),( Chang Seob Seo ),( Ying Li ),( Ye Jin ),( Xian Li ),( Seung Lark Hwang ),( Ok Yun Kwon ),( Young Chae Chang ),( Young Guk Park ) 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0
Saucerneol F (SF), a new tetrahydrofuran-type sesquilignan isolated from Saururus chinensis, dose-dependently inhibited nitric oxide (NO) production, with concomitant reduction of inducible nitric oxide synthase (iNOS) protein and mRNA expression in lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 cells. To elucidate the molecular mechanism underlying the inhibition of iNOSexpression by SF, we assessed the effects of SF on nuclear factor-κB (NF-κB) DNA-binding activity,NF-κB-dependent reporter gene activity, inhibitory factor-κB (IκB) phosphorylation and degradation, and p65 nuclear translocation. Treatment with SF decreased the luciferase activities of NF-κB reporter promoters in a dose-dependent manner and translocation of NF-κB p65. In addition, pretreatment of SF reduced LPS-stimulated activation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and c-Jun NH(2)-terminal kinase (JNK). Furthermore, SF attenuated the luciferase activities of AP-1 reporter promoters and the DNA-binding capacity of AP-1. Taken together, the present results indicate that SF attenuates NO production andiNOS expression by blocking LPS-induced activation of NF-κB, MAPKs, and AP-1, suggesting that SF is potentially applicable as an anti-inflammatory drug.ⓒ2011 Elsevier B.V.All rights reserved.
Yue Lu,Yan-Yan Zhang,Ying-Chun Hu,Yan-Hua Lu 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.9
2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone(DMC) is a chalcone isolated from the buds of Cleistocalyxoperculatus (Roxb.) Merr. et Perry, and thehepatoprotective effects of DMC on Kunming mice havebeen studied in previous study. However, the effects ofDMC on hepatocyte toxicity and corresponding mechanismremain unclear. The aim of this study was to evaluate thehepatoprotective mechanism of DMC in human hepatocytes(L02) treated with H2O2. The results demonstrated thatpretreatment with DMC effectively protected H2O2-inducedcell viability loss, cell membrane damage (lactate dehydrogenase,nitric oxide production and caspase-3 accumulation. Besides, DMC pretreatment increased the amount ofglutathione, decreased malondialdehyde and the percentageof apoptotic L02 cells compared with only H2O2 treatedgroup. Taken together, these results indicated that DMC hadhepatoprotective effects against H2O2-induced liver injuryby alleviating oxidative stress and apoptosis process in L02cells, and DMC might be a potential candidate for theintervention of liver diseases.
( Yue Lu ),( Min Kyun Na ),( Seok Jong Suh ),( Xian Li ),( Geum Jin Kim ),( Guang Hsuan Chao ),( Yong Tae Jeong ),( Dong Soo Kim ),( Young Chae Chang ),( Makoto Murakami ),( Wonku Kang ),( Cheorl Ho K 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
The purpose of this study is to investigate the effects of n-hexane extracts from bones and internalorgans of Japanese eel, Anguilla japonica (HEE), on cyclooxygenase-2 (COX-2)-dependent prostaglandin D₂(PGD₂) generation in stem cell factor (SCF), IL-10, plus LPS-induced mouse bone marrow-derived mast cells (BMMCs) and on passive cutaneous anaphylaxis (PCA) in mice. HEE suppressed SCF/IL-10/LPS-induced PGD₂ generation, and concomitantly reduced COX-2 protein expression dose-dependently. To understand the mechanistic basis for the inhibition of PGD₂ generation by HEE, we examined the effects of HEE on upstream signaling pathways essential for COX-2 induction. HEE was found to inhibit the translocation of nuclear factor-κB (NF-κB) p65 subunit to the nucleus and its DNA-binding ability through the inhibition of TAK1, IKK and IκB phosphorylation. Furthermore, HEE also attenuated mitogen-activated protein kinase (MAPK)-mediated regulation of DNA binding of activator protein-1 (AP-1). Moreover, oral administration of HEE inhibited anti-dinitrophenyl (DNP) IgE-induced PCA in a dose dependent manner. Taken together, the present study provides new insights into the anti-inflammatory activity of HEE, which could be a promising candidate to be used for an inflammatory therapy.ⓒ2013 Elsevier Ltd. All rights reserved.
( Yue Lu ),( Ying Li ),( Mei Hua Jin ),( Ju Hye Yang ),( Xian Li ),( Guang Hsuan Chao ),( Hyo Hyun Park ),( Young Na Park ),( Jong Keun Son ),( Eun Kyung Lee ),( Hyeun Wook Chang ) 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0
ETHNOPHARMACOLOGICAL RELEVANCE: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of bronchitis, digestive disorders, and inflammation. However, the mechanisms underlying its anti-inflammatory effects remain yet to be elucidated. The objectives of this study were 1) to assess the anti-allergic activity of the ethanol extract of flowers of Inula japonica extract (IFE) in vivo, 2) to investigate the mechanism of its action on mast cells in vitro, and 3) to identify its major phytochemical compositions. MATERIALS AND METHODS: The anti-allergic activity of IFE was evaluated using mouse bone marrow-derived mast cells (BMMCs) in vitro and a passive cutaneous anaphylaxis (PCA) animal model in vivo. The effects of IFE on mast cell activation were evaluated in terms of degranulation, eicosanoid generation, Ca(2+) influx, and immunoblotting of various signaling molecules. RESULTS: IFE inhibited degranulation and the generation of eicosanoids (PGD(2) and LTC(4)) in stem cell factor (SCF)-stimulated BMMCs. Biochemical analysis of the SCF-mediated signaling pathways demonstrated that IFE inhibited the activation of multiple downstream signaling processes including mobilization of intracellular Ca(2+) and phosphorylation of the mitogen-activated protein kinases (MAPKs), PLCγ1, and cPLA(2) pathways. When administered orally, IFE attenuated themast cell-mediated PCA reaction in IgE-sensitized mice. Its major phytochemical composition included three sesquiterpenes, 1-O-acetylbritannilactone, britanin and tomentosin. CONCLUSIONS: This study suggests that IFE modulates eicosanoids generation and degranulation through the suppression of SCF-mediated signaling pathways that would be beneficial for the prevention of allergic inflammatory diseases. Anti-allergic activity of IFE may be in part attributed particularly to the presence of britanin and tomentosin as major components evidenced by a HPLC analysis. Crown Copyright ⓒ2012 Published by Elsevier lreland Ltd. All rights reserved.
( Yue Lu ),( Jong Keun Son ),( Hyeun Wook Chang ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
During our on-going studies to identify bioactive compounds in medicinal herbs, we found that saucerneol F (SF), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4), cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2), and on phospholipase Cγ1 (PLCγ1)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid (PGD2 and LTC4) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of PLCγ1, intracellular Ca(2+) influx, the translocation of cytosolic phospholipase A2 (cPLA2) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular Ca(2+) influx by inhibiting PLCγ1 phosphorylation and suppressing the nuclear translocations of cPLA2 and 5-LO via the phosphorylations of MAPKs, including extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation.
( Yue Lu ),( Ying Li ),( Yurn Dong Jahng ),( Jong Keun Son ),( Hyeun Wook Chang ) 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0
The aim of this study was to evaluate whether citreorosein (CIT), a naturally occurring anthraquinone isolated from Polygoni cuspidati (P. cuspidati) radix, modulates degranulation and 5-lipoxygenase (5-LO)-dependent leukotriene C(4) (LTC(4)) generation in mast cells. Cit suppresses both degranulationand the generation of LTC(4) in a dose-dependent manner in stem cell factor (SCF)-mediated mouse bone marrow-derived mast cells (BMMCs). With regard to its molecular mechanism of action, we investigated the effects of CIT on intracellular signaling and mast cell activation employing BMMCs. Binding of SCF to c-Kit on mast cell membranes induced increases in intrinsic tyrosine kinase Syk activity and activation of multiple downstream events including phosphorylation of phospholipase Cγ (PLCγ), mobilization of intracellular Ca(2+), phosphatidylinositol 3-kinase (PI3K), Akt, MAP kinases (MAPKs), translocation of phospho-phospholipase A(2) (PLA(2)) and 5-LO. The results from the biochemical analysis demonstrate that CIT attenuates degranulation and LTC(4) generation through the suppression of multiple step signaling and would be beneficial for the prevention of allergic inflammation.
( Yue Lu ),( Seung Lark Hwang ),( Jong Keun Son ),( Hyeun Wook Chang ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
The authors investigated the effect of manassantin B (Man B) isolated from Saururus chinensis (S.chinensis) on cyclooxygenase-2 (COX-2)-dependent prostaglandin D2 (PGD2) generation in mouse bone marrow derived-mast cells (BMMCs). Man B inhibited the generation of PGD2 dose-dependently by inhibiting COX-2 expression in immunoglobulin E (IgE)/Ag-stimulated BMMCs. To elucidate the mechanism responsible for the inhibition of COX-2 expression by Man B, the effects of Man B on the activation of nuclear factor-kappaB (NF-κB), a transcription factor essential and mitogen-activated protein kinases (MAPKs) for COX-2 induction, were examined. Man B attenuated the nuclear translocation of NF-κB p65 and its DNA-binding activity by inhibiting inhibitors of kappa Bα (IκBα) degradation and concomitantly suppressing IκB kinase (IKK) phosphorylation. In addition, Man Bsuppressed phosphorylation of MAPKs including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK) and p38. It was also found that Man B suppressed Fyn kinase activation and consequent downstream signaling processes, including those involving Syk, Gab2, and Akt. Taken together, the present results suggest that Man B suppresses COX-2 dependent PGD2 generation by primarily inhibiting Fyn kinase in FcεRI-mediated mast cells.
Description of China Clothing Brand's Development and Changes of Late Years
Lu, Aluna Yue The Korean Society of Costume 2012 International journal of costume and fashion Vol.12 No.2
The purpose of study is to understand of china clothing brand to have them to be competitive position in global market. Also through this study people who are in a clothing industry market from China and overseas will be able to utilize it to have competitive brand power. Analyzing of the China clothing brand with a history and process of development is done to help understand of changes through years. With the rapid development of economy in China, the textiles & clothing industry, as one of the key industries, is showing a strong growing tendency, and brand in china have been expanding oversea market. Till 2002, China has already been the world's largest supplier of textile & clothing. Nowadays, "Made in China" is going to be "Created in China", lots of Chinese clothing brands appear, and many Chinese fashion designers step onto world stage. Chinese women's clothing, men's clothing, casual clothing, sports clothing and designer's brand are developing, popular brands are also promoted through convenient e-commerce. Clothing companies are going public, acquiring overseas brands, implementing internal mergers and integration, expanding overseas market. In such a diversity era, Chinese brands not only need to be localization, but also need to confirm with the trend of international management and globalized economy.
( Yue Lu ),( Jong Keun Son ),( Hyeun Wook Chang ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.6
During our on-going studies to identify bioactive compounds in medicinal herbs, we found that saucerneol F (SF), a naturally oc-curring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4), cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2), and on phospholipase Cg1 (PLCg1)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid (PGD2 and LTC4) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of PLCg1, intracellular Ca2+ influx, the translocation of cytosolic phospholipase A2 (cPLA2) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular Ca2+ influx by inhibiting PLCg1 phosphorylation and suppressing the nuclear translocations of cPLA2 and 5-LO via the phosphorylations of MAPKs, in-cluding extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation.