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        LPS로 염증 유도된 RAW 264.7세포에 대한 참콩풍뎅이(Popillia flavosellata) 에탄올 추출물의 항염증 효과

        윤영일(Young-Il Yoon),황재삼(Jae-Sam Hwang),김미애(Mi-Ae Kim),안미영(Mi Young Ahn),이영보(Young-Bo Lee),한명세(Myung Sae Han),구태원(Tae-Won Goo),윤은영(Eun-Young Yun) 한국생명과학회 2015 생명과학회지 Vol.25 No.9

        본 연구에서는 참콩풍뎅이(Popillia flavosellata) 에탄올 추출물(PFE)의 항염증 효능을 분석하기 위해 PFE를 농도별(500, 1,000, 2,000 ㎍/ml)로 대식세포인 RAW 264.7에 처리 시 최고 처리농도인 2,000 ㎍/ml까지 통계적인 유의성 있는 독성이 없음을 확인하였다. LPS (100 ng/ml)로 염증 유도된 RAW 264.7 세포에 PFE를 농도별(500, 1,000, 2,000 ㎍/ml)로 동시 처리 시 농도 의존적으로 염증성사이토카인인 TNF-α와 IL-6의 단백질 생성을 통계적인 유의성(p<0.001)있게 억제함을 확인하였다. 또한 염증 유도된 RAW 264.7 세포에 PFE 동시 처리 시 NF-κB p65의 핵으로 이동이 차단됨과 iNOS와 COX-2의 단백질 발현을 감소시키는 것을 확인하였다. 이상의 연구결과를 통해 참콩풍뎅이는 염증에 의해 활성화된 TLR-4 신호전달과정을 조절하는 NF-κB p65의 활성과 염증성사이토카인 TNF-α와 IL-6의 생성 및 염증성효소 iNOS와 COX-2의 생성을 억제하는 항염증 효능이 있음을 확인하였다. The beetle Popillia flavosellata has been no reported its functional effects. In this study, we investigated the anti-inflammatory effect of P. flavosellata ethanol extract (PFE) on RAW 264.7 mouse macrophage cells treated with lipopolysaccharide (LPS) for the induction of inflammation. First, we examined the cytotoxicity of PFE in the RAW 264.7 cells at a concentration of 2,000 μg/ml or less. To evaluate the anti-inflammatory effects of PFE, we investigated the expression levels of proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, and proinflammatory enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW 264.7 cells. In addition, we examined whether PFE inhibited the translocation of nuclear factor kappa B (NF-κB) p65 into the nucleus in the LPS-induced RAW 264.7 cells. We found that the protein levels of TNF-α and IL-6 were decreased in the LPS-induced RAW 264.7 cells after the treatment with PFE in a dose-dependent manner. In addition, we confirmed that PFE inhibited the translocation of NF-κB p65 into the nucleus, as well as the protein expression levels of iNOS and COX-2. Accordingly, we propose that PFE exerts an anti-inflammatory effect through the down-regulation of NF-κB p65, TNF-α, IL-6, iNOS, and COX-2 via the toll like receptor (TLR)-4 inflammatory signaling pathway.

      • SCISCIESCOPUS

        Caffeic acid phenethyl ester inhibits the inflammatory effects of interleukin-1β in human corneal fibroblasts

        Yang, Jae-Wook,Jung, Won-Kyo,Lee, Chang-Min,Yea, Sung Su,Choi, Yung Hyun,Kim, Gi-Young,Lee, Dae-Sung,Na, Giyoun,Park, Sae-Gwang,Seo, Su-Kil,Choi, Jung Sik,Lee, Young-Min,Park, Won Sun,Choi, Il-Whan Informa Healthcare USA, Inc. 2014 IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY Vol.36 No.5

        <P><I>Context</I>: Expression of various inflammatory mediators in corneal fibroblasts contributes to corneal inflammation.</P><P><I>Objective</I>: The purpose of this study was to assess the possible effects of caffeic acid phenethyl ester (CAPE) on the expression of inflammatory mediators during an inflammatory response in human corneal fibroblasts.</P><P><I>Materials and methods</I>: The levels of interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule-1 (ICAM-1) from IL-1β-exposed human corneal fibroblasts were measured with enzyme-linked immunosorbent assays (ELISA). The regulatory mechanisms of CAPE on cellular signaling pathways were examined using Western blot and electrophoretic mobility shift assays. A functional validation was carried out by evaluating the inhibitory effects of CAPE on neutrophil and monocyte migration <I>in vitro</I>.</P><P><I>Results</I>: CAPE inhibited the expression of IL-6, MCP-1 and ICAM-1 induced by the pro-inflammatory cytokine IL-1β in corneal fibroblasts. The activation of AKT and NF-κB by IL-1β was markedly inhibited by CAPE, whereas the activity of mitogen-activated protein kinases (MAPKs) was not affected. CAPE significantly suppressed the IL-1β-induced migration of differentiated (d)HL-60 and THP-1 cells.</P><P><I>Discussion</I>: These anti-inflammatory effects of CAPE may be expected to inhibit the infiltration of leukocytes into the corneal stroma <I>in vivo</I>.</P>

      • Inhibitory Effects of Traditional Herbal Formula Pyungwi-San on Inflammatory Response <i>In Vitro</i> and <i>In Vivo</i>

        Cha, Ji Young,Jung, Ji Yun,Jung, Jae Yup,Lee, Jong Rok,Cho, Il Je,Ku, Sae Kwang,Byun, Sung Hui,Ahn, Yong-Tae,Lee, Chul Won,Kim, Sang Chan,An, Won G. Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

        <P>Pyungwi-san (PWS) is a traditional basic herbal formula. We investigated the effects of PWS on induction of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-<I><I>α</I></I> (TNF-<I><I>α</I></I>)) and nuclear factor-kappa B (NF-<I><I>κ</I></I>B) as well as mitogen-activated protein kinases (MAPKs) in lipopolysaccharide-(LPS-) induced Raw 264.7 cells and on paw edema in rats. Treatment with PWS (0.5, 0.75, and 1 mg/mL) resulted in inhibited levels of expression of LPS-induced COX-2, iNOS, NF-<I><I>κ</I></I>B, and MAPKs as well as production of prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>), nitric oxide (NO), IL-6, and TNF-<I><I>α</I></I> induced by LPS. Our results demonstrate that PWS possesses anti-inflammatory activities via decreasing production of pro-inflammatory mediators through suppression of the signaling pathways of NF-<I><I>κ</I></I>B and MAPKs in LPS-induced macrophage cells. More importantly, results of the carrageenan-(CA-) induced paw edema demonstrate an anti-edema effect of PWS. In addition, it is considered that PWS also inhibits the acute edematous inflammations through suppression of mast cell degranulations and inflammatory mediators, including COX-2, iNOS and TNF-<I><I>α</I></I>. Thus, our findings may provide scientific evidence to explain the anti-inflammatory properties of PWS <I>in vitro</I> and <I>in vivo</I>.</P>

      • SCISCIESCOPUS

        Effects of <i>Ecklonia cava</i> ethanolic extracts on airway hyperresponsiveness and inflammation in a murine asthma model: Role of suppressor of cytokine signaling

        Kim, Se-Kwon,Lee, Da-Young,Jung, Won-Kyo,Kim, Ji-Hye,Choi, Inhak,Park, Sae-Gwang,Seo, Su-Kil,Lee, Soo-Woong,Lee, Chang Min,Yea, Sung Su,Choi, Yung Hyun,Choi, Il-Whan Elsevier 2008 BIOMEDICINE AND PHARMACOTHERAPY Vol.62 No.5

        <P><B>Abstract</B></P><P><I>Ecklonia cava</I> (EC) is a brown alga that evidences radical scavenging activity, bactericidal activity, tyrosinase inhibitory activity, and protease inhibitory activity. However, its anti-allergic effects remain poorly understood. In the current study, we attempted to determine whether pretreatment with EC induces a significant inhibition of asthmatic reactions in a mouse asthma model. Mice sensitized and challenged with ovalbumin (OVA) evidenced typical asthmatic reactions, as follows: an increase in the number of eosinophils in bronchoalveolar lavage fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways, and airway luminal narrowing; the development of airway hyperresponsiveness; the detection of tumor necrosis factor-alpha (TNF-α) and Th2 cytokines, including IL-4 and IL-5 in the bronchoalveolar lavage (BAL) fluid; and the detection of allergen-specific immunoglobulin E (IgE) in the serum. However, the administration of EC extract prior to the final airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. We also demonstrated that EC extracts treatment resulted in significant reductions on matrix metalloproteinase-9 (MMP-9) and Suppressor of cytokine signaling-3 (SOCS-3) expression and a reduction in the increased eosinophil peroxidase (EPO) activity. The treatment of animals with EC extracts resulted in a significant reduction in the concentrations of the Th2 cytokine (IL-4 and IL-5) in the airways, without any concomitant increase in the concentration of Th1 cytokines. These findings indicate that EC extracts may prove useful as an adjuvant therapy for allergic airway reactions via the inhibition of the Th2 response. Accordingly, this study may provide evidence that EC extract performs a critical function in the amelioration of the pathogenetic process of asthma in mice.</P>

      • SCIESCOPUS

        Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells

        Cho, Mi Suk,Park, Won Sun,Jung, Won-Kyo,Qian, Zhong-ji,Lee, Dae-Sung,Choi, Jung-Sik,Lee, Da-Young,Park, Sae-Gwang,Seo, Su-Kil,Kim, Hak-Ju,Won, Jun Yeon,Yu, Byeng Chul,Choi, Il-Whan Informa Healthcare USA, Inc. 2014 PHARMACEUTICAL BIOLOGY Vol.52 No.7

        <P><I>Context</I>: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown.</P><P><I>Objective</I>: The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells <I>in vitro</I>.</P><P><I>Materials and methods</I>: To investigate the bioactive potential of CAPE (10 or 20 µM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used.</P><P><I>Results</I>: CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 µM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1β (4.775 versus 0.713 pg/ml, IC<SUB>50</SUB> = 6.67 µM), IL-6 (4771.5 versus 449.1 pg/ml, IC<SUB>50</SUB> = 5.25 µM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC<SUB>50</SUB> = 9.95 µM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation.</P><P><I>Discussion and conclusion</I>: Our results indicated that CAPE can modulate mast cell-mediated allergic disease.</P>

      • Amelioration of inflammatory responses by <i>Socheongryong-Tang</i> , a traditional herbal medicine, in RAW 264.7 cells and rats

        Park, Sang Mi,Lee, Tae Hoon,Zhao, Rongjie,Kim, Youn Sook,Jung, Ji Yun,Park, Chung A.,Jegal, Kyung Hwan,Ku, Sae Kwang,Kim, Jae Kwang,Lee, Chul Won,Kim, Young Woo,Cho, Il Je,An, Won G.,Kim, Sang Chan D.A. Spandidos 2018 International journal of molecular medicine Vol.41 No.5

        <P>Socheongryong-Tang (SCRT) is a natural medicine prescription that has been mainly used in East Asia for the treatment of inflammatory disorders, including asthma and allergic rhinitis. The present study evaluated the anti-inflammatory effects of SCRT on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in a rat model of carrageenan (CA)-induced paw edema. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) in the culture supernatant were quantified and nitric oxide (NO) production was monitored. In addition, the effect of SCRT on the protein expression of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was assessed by western blot analysis. Furthermore, the effects of SCRT on acute inflammation <I>in vivo</I> and changes in the histomorphometry and histopathology of paw skin were observed using CA-treated rats. SCRT (1 mg/ml) inhibited the LPS-induced changes in the protein expression of NF-κB, JNK, ERK1/2, iNOS and COX-2, as well as the production of NO, PGE<SUB>2</SUB> and cytokines. In the rat paw edema assay, administration of 1 g/kg of lyophilized powder obtained from the aqueous extracts of SCRT for 3 consecutive days inhibited the CA-induced increases in skin thickness, mast cell degranulation, and infiltration of inflammatory cells in the ventral and dorsal pedis skin within 4 h. These results demonstrated that SCRT exerts its anti-inflammatory activities in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, including PGE<SUB>2</SUB>, NO and cytokines, via suppression of the NF-κB and JNK and ERK1/2 signaling pathways. In addition, the data of the CA-induced paw edema indicated an anti-edema effect of SCRT. SCRT (1 g/kg) reduced acute edematous inflammation through inhibition of mast cell degranulation and infiltration of inflammatory cells. Therefore, the present study provided scientific evidence for the anti-inflammatory activities of SCRT as well as the underlying mechanisms.</P>

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