Effects of Gintonin-Enriched Fraction in an Atopic Dermatitis Animal Model: Involvement of Autotaxin Regulation

Ginseng extract has been used for prevention of atopic dermatitis (AD) in experimental animal models. However, little is known about its active ingredients and the molecular mechanisms underlying its anti-AD effects. Recently, we isolated a unique lysophosphatidic acid (LPA) receptor ligand, gintoni...

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Veröffentlicht in:Biological & pharmaceutical bulletin 2017/07/01, Vol.40(7), pp.1063-1070
Hauptverfasser: Lee, Byung-Hwan, Kim, Ho-Kyoung, Jang, Minhee, Kim, Hyeon-Joong, Choi, Sun-Hye, Hwang, Sung-Hee, Kim, Hyoung-Chun, Rhim, Hyewhon, Cho, Ik-Hyun, Nah, Seung-Yeol
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container_issue 7
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container_title Biological & pharmaceutical bulletin
container_volume 40
creator Lee, Byung-Hwan
Kim, Ho-Kyoung
Jang, Minhee
Kim, Hyeon-Joong
Choi, Sun-Hye
Hwang, Sung-Hee
Kim, Hyoung-Chun
Rhim, Hyewhon
Cho, Ik-Hyun
Nah, Seung-Yeol
description Ginseng extract has been used for prevention of atopic dermatitis (AD) in experimental animal models. However, little is known about its active ingredients and the molecular mechanisms underlying its anti-AD effects. Recently, we isolated a unique lysophosphatidic acid (LPA) receptor ligand, gintonin, from ginseng. Gintonin, the glycolipoprotein fraction of ginseng, contains LPAs, mainly LPA C18 : 2 with other minor lysophospholipid components. A line of evidence showed that serum autotaxin (ATX) activity and level are significantly elevated in human AD patients compared to those in normal controls, which indicates that ATX may be involved in human AD. In a previous study, we demonstrated that gintonin exerted anti-inflammatory effects via inhibition of microglial activation and proinflammatory cytokine production by immune cells and that it strongly inhibited ATX activity. In this study, we investigated whether oral administration of the gintonin-enriched fraction (GEF) could ameliorate the symptoms of 2,4-dinitrofluorobenzene (DNFB)-induced AD in NC/Nga mice. We found that oral administration of GEF to DNFB-induced AD mice for 2 weeks reduced ear swelling and AD skin index. In addition, oral administration of GEF reduced the serum levels of immunoglobulin E, histamine, interleukin-4, and interferon-γ. Histological examination showed that oral administration of GEF attenuated skin inflammation and significantly reduced eosinophil and mast cell infiltration into the skin. Moreover, oral administration of GEF not only decreased serum ATX level but also reduced serum ATX activity. The present study shows that the anti-AD effects of ginseng might be attributed to GEF-induced anti-inflammatory activity and ATX regulation.
doi_str_mv 10.1248/bpb.b17-00124
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However, little is known about its active ingredients and the molecular mechanisms underlying its anti-AD effects. Recently, we isolated a unique lysophosphatidic acid (LPA) receptor ligand, gintonin, from ginseng. Gintonin, the glycolipoprotein fraction of ginseng, contains LPAs, mainly LPA C18 : 2 with other minor lysophospholipid components. A line of evidence showed that serum autotaxin (ATX) activity and level are significantly elevated in human AD patients compared to those in normal controls, which indicates that ATX may be involved in human AD. In a previous study, we demonstrated that gintonin exerted anti-inflammatory effects via inhibition of microglial activation and proinflammatory cytokine production by immune cells and that it strongly inhibited ATX activity. In this study, we investigated whether oral administration of the gintonin-enriched fraction (GEF) could ameliorate the symptoms of 2,4-dinitrofluorobenzene (DNFB)-induced AD in NC/Nga mice. We found that oral administration of GEF to DNFB-induced AD mice for 2 weeks reduced ear swelling and AD skin index. In addition, oral administration of GEF reduced the serum levels of immunoglobulin E, histamine, interleukin-4, and interferon-γ. Histological examination showed that oral administration of GEF attenuated skin inflammation and significantly reduced eosinophil and mast cell infiltration into the skin. Moreover, oral administration of GEF not only decreased serum ATX level but also reduced serum ATX activity. 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We found that oral administration of GEF to DNFB-induced AD mice for 2 weeks reduced ear swelling and AD skin index. In addition, oral administration of GEF reduced the serum levels of immunoglobulin E, histamine, interleukin-4, and interferon-γ. Histological examination showed that oral administration of GEF attenuated skin inflammation and significantly reduced eosinophil and mast cell infiltration into the skin. Moreover, oral administration of GEF not only decreased serum ATX level but also reduced serum ATX activity. 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dosage</subject><subject>Plant Extracts - therapeutic use</subject><subject>Rodents</subject><subject>Serum levels</subject><subject>Skin</subject><subject>γ-Interferon</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc9vFCEUx4nR2LV69GpIvHiZyu9hvG3W7dqkxsTomTAM07JhYAWmqf-9zG5dEzk8IO_D9z3eF4C3GF1hwuTH_tBf9bhtEKrXZ2CFKWsbTjB_Dlaow7IRmMsL8CrnPUKoRYS-BBdEipYR1q1A3I6jNSXDOMKdCyUGF5ptSM7c2wFeJ22KiwG6AHWA6xIPzsDPNk26uOIyXAc3aQ-_xsH6T_AmPET_YCcbyqK3nkss-rG-_W7vZq8Xpdfgxah9tm-e9kvw83r7Y_Oluf22u9msbxtTWyyN4JKwUSOuRyKQ7k0rDUGECCOtlb2grGsJoRRL2o8Drue6Os0xwcNAsaaX4MNJ95Dir9nmoiaXjfVeBxvnrHBXxyIJp6yi7_9D93FOoXa3UAJ1nDFRqeZEmRRzTnZUh1T_nn4rjNTihKpOqOqEOjpR-XdPqnM_2eFM_x19BXYnoGad0T4G74L9V9vktnfRR0XQUZRV9xTCvNYTtIY6pw5xgdqqtDkp7XPRd_ZcSqfijLfHxhhS7RLODZ6z5l4nZQP9A3TisS0</recordid><startdate>2017</startdate><enddate>2017</enddate><creator>Lee, Byung-Hwan</creator><creator>Kim, Ho-Kyoung</creator><creator>Jang, Minhee</creator><creator>Kim, Hyeon-Joong</creator><creator>Choi, Sun-Hye</creator><creator>Hwang, Sung-Hee</creator><creator>Kim, Hyoung-Chun</creator><creator>Rhim, Hyewhon</creator><creator>Cho, Ik-Hyun</creator><creator>Nah, Seung-Yeol</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>2017</creationdate><title>Effects of Gintonin-Enriched Fraction in an Atopic Dermatitis Animal Model: Involvement of Autotaxin Regulation</title><author>Lee, Byung-Hwan ; Kim, Ho-Kyoung ; Jang, Minhee ; Kim, Hyeon-Joong ; Choi, Sun-Hye ; Hwang, Sung-Hee ; Kim, Hyoung-Chun ; Rhim, Hyewhon ; Cho, Ik-Hyun ; Nah, Seung-Yeol</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c702t-65824fa05af260abc78c20226c8ee8b634972233183bfd17222229a5121dd31a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Administration, Oral</topic><topic>Animal models</topic><topic>Animals</topic><topic>anti-atopic dermatitis</topic><topic>Anti-inflammatory agents</topic><topic>Atopic dermatitis</topic><topic>autotaxin</topic><topic>Case-Control Studies</topic><topic>Dermatitis</topic><topic>Dermatitis, Atopic - chemically induced</topic><topic>Dermatitis, Atopic - drug therapy</topic><topic>Dermatitis, Atopic - metabolism</topic><topic>Dinitrofluorobenzene</topic><topic>Dinitrofluorobenzene - administration &amp; dosage</topic><topic>Disease Models, Animal</topic><topic>Ear</topic><topic>Eczema</topic><topic>Ginseng</topic><topic>gintonin</topic><topic>Histamine</topic><topic>Immunoglobulin E</topic><topic>Inflammation</topic><topic>Interferon</topic><topic>Interleukin 4</topic><topic>Leukocytes (eosinophilic)</topic><topic>Lysophosphatidic acid</topic><topic>Male</topic><topic>Mice</topic><topic>Molecular modelling</topic><topic>Oral administration</topic><topic>Panax ginseng</topic><topic>Phosphoric Diester Hydrolases - blood</topic><topic>Plant Extracts - administration &amp; 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pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2017</date><risdate>2017</risdate><volume>40</volume><issue>7</issue><spage>1063</spage><epage>1070</epage><pages>1063-1070</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>Ginseng extract has been used for prevention of atopic dermatitis (AD) in experimental animal models. 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We found that oral administration of GEF to DNFB-induced AD mice for 2 weeks reduced ear swelling and AD skin index. In addition, oral administration of GEF reduced the serum levels of immunoglobulin E, histamine, interleukin-4, and interferon-γ. Histological examination showed that oral administration of GEF attenuated skin inflammation and significantly reduced eosinophil and mast cell infiltration into the skin. Moreover, oral administration of GEF not only decreased serum ATX level but also reduced serum ATX activity. The present study shows that the anti-AD effects of ginseng might be attributed to GEF-induced anti-inflammatory activity and ATX regulation.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>28674249</pmid><doi>10.1248/bpb.b17-00124</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Administration, Oral
Animal models
Animals
anti-atopic dermatitis
Anti-inflammatory agents
Atopic dermatitis
autotaxin
Case-Control Studies
Dermatitis
Dermatitis, Atopic - chemically induced
Dermatitis, Atopic - drug therapy
Dermatitis, Atopic - metabolism
Dinitrofluorobenzene
Dinitrofluorobenzene - administration & dosage
Disease Models, Animal
Ear
Eczema
Ginseng
gintonin
Histamine
Immunoglobulin E
Inflammation
Interferon
Interleukin 4
Leukocytes (eosinophilic)
Lysophosphatidic acid
Male
Mice
Molecular modelling
Oral administration
Panax ginseng
Phosphoric Diester Hydrolases - blood
Plant Extracts - administration & dosage
Plant Extracts - therapeutic use
Rodents
Serum levels
Skin
γ-Interferon
title Effects of Gintonin-Enriched Fraction in an Atopic Dermatitis Animal Model: Involvement of Autotaxin Regulation
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