Anti-inflammatory Effects of KOTMIN13: A Mixed Herbal Medicine in LPS-stimulated RAW 264.7 Cells and Mouse Edema Models

Lee, Eujin,Kim, Sun-Gun,Park, Na-Young,Park, Hyo-Hyun,Jeong, Kyu-Tae,Choi, Jongkeun,Lee, In-Hae,Lee, Hwadong,Lee, Eunkyung Medknow PublicationsMedia Pvt Ltd 2017 Pharmacognosy magazine Vol.13 No.50

<P><B>Background:</B></P><P>A Korean herbal medicine, KOTMIN13, composed of <I>Inula japonica</I> Thunberg, <I>Trichosanthes kirilowii Maximowicz</I> var. <I>japonica kitamura</I>, <I>Peucedanum praeruptorum</I> Dunn, and <I>Allium macrostemon</I> Bge, has been used for anti-allergic and anti-asthmatic treatment in oriental clinics, but its activity has not been investigated.</P><P><B>Materials and Methods:</B></P><P>To evaluate the anti-inflammatory activity of KOTMIN13 for <I>in vitro</I> study, LPS-stimulated RAW 264.7 cells were used to induce the production and expression of inflammatory mediators and its mechanisms. 12-<I>O</I>-Tetradecanoylphorobol-13 aceate (TPA)-induced ear edema and carrageenan-induced paw edema models were also used to evaluate the effect of KOTMIN13 on acute inflammation <I>in vivo</I>.</P><P><B>Results:</B></P><P>KOTMIN13 reduced the release of inflammatory mediators [nitric oxide, prostaglandin E2, interleukin (IL)-1β, and IL-6] and the protein expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells. Mechanism studies showed the attenuation of LPS-induced NF-κB activation by KOTMIN13 via IκBα degradation abrogation and a subsequent decrease in nuclear p65 levels. Activation of mitogen-activated protein kinases (ERK, JNK, and p38) was also suppressed. Furthermore, KOTMIN13 ameliorated the development of TPA-induced ear edema and carrageenan-induced paw edema in acute inflammatory edema mouse models.</P><P><B>Conclusion:</B></P><P>Our study demonstrates that KOTMIN13 inhibits inflammatory mediators through the inhibitions of NF-κB and MAPK activities in LPS-induced RAW 264.7 cells, as well as acute inflammation in edema models, indicating that KOTMIN13 is an effective suppressor for anti-inflammatory activities.</P><P><B>SUMMARY</B></P><P><P>KOTMIN13 decrease the production of No, PGE<SUB>2</SUB>, and proinflammatory cytokine (TNF-∝, IL-1β,IL-6).</P><P>KOTMIN13 Suppressed the degradation of NF-kβ and IKβα and the phosorylation of MAP Kinases.</P><P>Topical application of KOTMIN13 reduced mouse ear edema.</P><P>Oral administration of KOTMIN13 decreased carrageenan-induced paw edema.</P></P> >[FIG OMISSION]</BR><P><B>Abbreviations used:</B> NO: nitric oxide; PGE2: prostaglandin E2; iNOS: inducible NO synthase; COX-2: cyclooxygenase-2; TNF-α: tumor necrosis factor-α; IL: interleukin; NF-κB: nuclear factor kappaB; MAPK: mitogen-activated protein kinases; ERK: extracellular signal regulated kinase; JNK: c-jun N terminal kinase; TPA: 12-O-tetradecanoylphorbol-13-acetate</P>

Methionine sulfoxide reductase B3 deficiency inhibits cell growth through the activation of p53-p21 and p27 pathways

Lee, Eujin,Kwak, Geun-Hee,Kamble, Kranti,Kim, Hwa-Young Elsevier 2014 Archives of biochemistry and biophysics Vol.547 No.-

Effects of Repeated Nicotine Treatment on the Changes in Glutamate Receptor Subunits Levels in Mesocorticolimbic Dopamine Areas

Kuem-Ju Lee,Dong-Hoon Kim,Song-Hyen Choi,You-Chan Shin,Sang-Ha Park,Bo-Hyun Moon,Seung Woo Kang,Eujin Cho,Sang-Hyun Choi,Boe-Gwun Chun,Min-Soo Lee,Kyung-Ho Shin 대한생리학회-대한약리학회 2007 The Korean Journal of Physiology & Pharmacology Vol.20 No.3

Recent studies suggest that alterations in glutamate receptor subunit levels in mesocorticolimbic dopamine areas could account for neural adaptations in response to psychostimulant drugs. Although many drugs of abuse induce changes in ionotropic glutamate receptor subunits in mesocorticolimbic dopamine areas, the changes of ionotropic glutamate receptor subunits by repeated nicotine treatment in these areas are not known. To answer this question, we injected male Sprague-Dawley rats twice daily with nicotine (0.4 mg/kg) or saline (1 ml/kg) for 10 days. The immunoreactivity of NR1, GluR1, and GluR2 glutamate receptor subunits was examined 16∼18 h after the last injection of saline or nicotine. Repeated nicotine treatment significantly increased NR1 levels in the ventral tegmental area (VTA). In addition, repeated nicotine treatment showed a tendency towards an increase in GluR1 levels in the VTA as well as in striatum. However, there was no significant change in glutamate receptor subunits in other areas including nucleus accumbens (NAc). These results demonstrate that repeated nicotine treatment increases NR1 levels in VTA similarly to other drugs of abuse, suggesting that elevated glutamate receptor subunits in the VTA, but not NAc may be involved in the excitation of mesocorticolimbic dopamine neurons by nicotine.

대용량 웹에서 RCS를 이용한 웹 히스토리 저장 시스템 설계

이무훈(Moonhun Lee),이민희(Minhee Lee),조성훈(Sunghoon Cho),장창복(Changbok Jang),김동혁(Donghyuk Kim),최의인(Eujin Choi) 한국정보과학회 2004 한국정보과학회 학술발표논문집 Vol.31 No.1B

웹의 급속한 성장에 따라 웹 정보는 시간적·공간적 제약을 받지 않고 널리 활용되어지고 있다. 하지만 기존에 유용하게 사용되던 정보가 어느 순간 삭제가 된다면 더 이상 웹 정보를 이용할 수 없게 된다는 문제점이 존재한다. 이러한 문제를 해결하기 위해 웹 아카이브 시스템에 대한 연구와 좀더 효율적으로 삭제된 웹 정보를 저장하기 위한 기법들이 제안되었다. 그러나 기존의 기법들은 단순히 웹 정보를 저장하는 것에만 초점을 두었기 때문에 저장 공간의 효율성 및 제약성을 전혀 고려하지 않는 단점을 가지고 있다. 따라서 본 논문에서는 WebBase를 기반으로 하여 레포지토리에서 갱신되는 웹 정보들을 효율적으로 저장하고 검색할 수 있는 웹 히스토리 저장 시스템을 설계하였다. 본 논문에서 제안한 기법은 웹 히스토리 저장 시스템 설계를 위해 별도의 Crawler를 두지 않고 WebBase를 활용함으로써 웹 정보 수집에 대한 오버헤드를 줄일 수 있고, 삭제되는 웹 정보를 RCS를 통하여 체계적이고 효율적으로 저장함으로써 중요한 웹 정보를 공유할 수 있도록 하였다.

Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells

Jeong, Kyu-Tae,Lee, Eujin,Park, Na-Young,Kim, Sun-Gun,Park, Hyo-Hyun,Lee, Jiean,Lee, Youn Ju,Lee, Eunkyung The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.5

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells

( Kyu-tae Jeong ),( Eujin Lee ),( Na-young Park ),( Sun-gun Kim ),( Hyo-hyun Park ),( Jiean Lee ),( Youn Ju Lee ),( Eunkyung Lee ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.5

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cγ1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-κB pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

Methionine sulfoxide reductase B3 deficiency causes hearing loss due to stereocilia degeneration and apoptotic cell death in cochlear hair cells

Kwon, Tae-Jun,Cho, Hyun-Ju,Kim, Un-Kyung,Lee, Eujin,Oh, Se-Kyung,Bok, Jinwoong,Bae, Yong Chul,Yi, Jun-Koo,Lee, Jang Woo,Ryoo, Zae-Young,Lee, Sang Heun,Lee, Kyu-Yup,Kim, Hwa-Young IRL Press 2014 Human molecular genetics Vol.23 No.6

<P>Methionine sulfoxide reductase B3 (MsrB3) is a protein repair enzyme that specifically reduces methionine-<I>R</I>-sulfoxide to methionine. A recent genetic study showed that the <I>MSRB3</I> gene is associated with autosomal recessive hearing loss in human deafness DFNB74. However, the precise role of MSRB3 in the auditory system and the pathogenesis of hearing loss have not yet been determined. This work is the first to generate <I>MsrB3</I> knockout mice to elucidate the possible pathological mechanisms of hearing loss observed in DFNB74 patients. We found that homozygous <I>MsrB3<SUP>−/−</SUP></I> mice were profoundly deaf and had largely unaffected vestibular function, whereas heterozygous <I>MsrB3<SUP>+/−</SUP></I> mice exhibited normal hearing similar to that of wild-type mice. The MsrB3 protein is expressed in the sensory epithelia of the cochlear and vestibular tissues, beginning at E15.5 and E13.5, respectively. Interestingly, MsrB3 is densely localized at the base of stereocilia on the apical surface of auditory hair cells. MsrB3 deficiency led to progressive degeneration of stereociliary bundles starting at P8, followed by a loss of hair cells, resulting in profound deafness in <I>MsrB3<SUP>−/−</SUP></I> mice. The hair cell loss appeared to be mediated by apoptotic cell death, which was measured using TUNEL and caspase 3 immunocytochemistry. Taken together, our data suggest that MsrB3 plays an essential role in maintaining the integrity of hair cells, possibly explaining the pathogenesis of DFNB74 deafness in humans caused by MSRB3 deficiency.</P>

Chlorin e6 Prevents ADP-Induced Platelet Aggregation by Decreasing PI3K-Akt Phosphorylation and Promoting cAMP Production

Park, Ji Young,Ji, Hyun Dong,Jeon, Bo Ra,Im, Eun Ju,Son, Young Min,Lee, Joo Young,Lee, Dong-Ha,Lee, Young-Chul,Hyun, Eujin,Jia, Qi,Hong, Mei,Park, Hwa-Jin,Rhee, Man Hee Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P>A number of reagents that prevent thrombosis have been developed but were found to have serious side effects. Therefore, we sought to identify complementary and alternative medicinal materials that are safe and have long-term efficacy. In the present studies, we have assessed the ability of chlorine e6 (CE6) to inhibit ADP-induced aggregation of rat platelets and elucidated the underlying mechanism. CE6 inhibited platelet aggregation induced by 10 <I>µ</I>M ADP in a concentration-dependent manner and decreased intracellular calcium mobilization and granule secretion (i.e., ATP and serotonin release). Western blotting revealed that CE6 strongly inhibited the phosphorylations of PI3K, Akt, c-Jun N-terminal kinase (JNK), and different mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2) as well as p38-MAPK. Our study also demonstrated that CE6 significantly elevated intracellular cAMP levels and decreased thromboxane A<SUB>2</SUB> formation in a concentration-dependent manner. Furthermore, we determined that CE6 initiated the activation of PKA, an effector of cAMP. Taken together, our findings indicate that CE6 may inhibit ADP-induced platelet activation by elevating cAMP levels and suppressing PI3K/Akt activity. Finally, these results suggest that CE6 could be developed as therapeutic agent that helps prevent thrombosis and ischemia.</P>

Disseminated adenovirus infection in a 10-year-old renal allograft recipient

( Eujin Park ),( Hee Gyung Kang ),( Hae Il Cheong ),( Il Soo Ha ),( Bora Lee ),( Jongwon Ha ) 대한신장학회 2018 Kidney Research and Clinical Practice Vol.37 No.4

어육장의 미생물학적 특성

오유진(Eujin Oh),오미화(Mi-Hwa Oh),이종미(Jong Mee Lee),조미숙(Mi Sook Cho),오상석(Sangsuk Oh) 한국식품과학회 2008 한국식품과학회지 Vol.40 No.6

예로부터 전통 장류는 먹거리로 많이 이용되어 왔으며, 최근에는 장류의 다양한 영양 성분 및 생리 활성 능력이 밝혀지면서 관심이 증대되고 있다. 본 연구에서는 전통 방식으로 제조된 어육장의 발효에 관여하는 미생물을 숙성 기간별로 분석하고 이를 통해 안전성을 평가하였으며, 이와 함께 국내에서 시판되고 있는 간장의 미생물을 분석하여 어육장의 미생물분석과 비교하였다. 어육장은 2개월 단위로 샘플링하여 분석하였으며, 분리된 미생물은 API kit와 16S rDNA sequencing을 이용하여 동정하였다. 어육장의 발효에 전반적으로 관여하는 미생물은 Bacillus 균류와 Saccharomyces cerevisiae였으며, 숙성 초기에는 Aspergillus flavus가 발효에 관여하는 것으로 확인되었다. 어육장은 최종적으로 섭취 전에 달이는 과정을 거치게 되는데 실험결과 달인 후에는 미생물이 존재하지 않았다. 현재 국내에서 시판되고 간장의 경우 총 균수가 0-42 CFU/mL였고, 동정결과 B. subtilis, B. licheniformis, B. pumilus로 확인되었다. 분리된 Bacillus 균류에 대하여 독소여부를 분석한 결과 어육장 및 시판 장류에서 검출된 Bacillus 균류는 본 실험에서 분석된 3가지 설사형 독소와 1종의 구토형 독소를 생성하지 않는 균주들인 것으로 확인되었다. Fermented soybean foods are an important component of the Korean diet. Eoyukjang is a type of traditional fermented soybean source. Microbial analysis of eoyukjang was conducted during the fermentation period in this study. Microorganisms isolated from eoyukjang were identified by biochemical tests and 16S rDNA sequencing. 17 different microorganisms, including bacteria, yeast, and fungi were detected in eoyukjang during the fermentation period. Even though Aspergillus participated in the early stage of fermentation of eoyukjang, Bacillus species and Saccharomyces cerevisiae were the major microzymes in eoyukjang throughout the maturation period. Eoyukjang is generally consumed after the boiling of the final sample. Therefore, the final sample of eoyukjang was boiled and analyzed. Our results showed that no vegetative microorganisms survived under the boiling conditions for eoyukjang. Fermented soybean products in the domestic market were also assessed for comparison with the results from eoyukjang. The total cell number of kanjang (soy sauce) samples was between 0 to 42 CFU/mL. The isolated microorganisms were identified as Bacillus species. All Bacillus isolates were not found to harbor the three enterotoxin-producing and emetic toxin-producing genes.