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 |
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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. The present study shows that the anti-AD effects of ginseng might be attributed to GEF-induced anti-inflammatory activity and ATX regulation.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b17-00124</identifier><identifier>PMID: 28674249</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>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</subject><ispartof>Biological and Pharmaceutical Bulletin, 2017/07/01, Vol.40(7), pp.1063-1070</ispartof><rights>2017 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c702t-65824fa05af260abc78c20226c8ee8b634972233183bfd17222229a5121dd31a3</citedby><cites>FETCH-LOGICAL-c702t-65824fa05af260abc78c20226c8ee8b634972233183bfd17222229a5121dd31a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28674249$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Byung-Hwan</creatorcontrib><creatorcontrib>Kim, Ho-Kyoung</creatorcontrib><creatorcontrib>Jang, Minhee</creatorcontrib><creatorcontrib>Kim, Hyeon-Joong</creatorcontrib><creatorcontrib>Choi, Sun-Hye</creatorcontrib><creatorcontrib>Hwang, Sung-Hee</creatorcontrib><creatorcontrib>Kim, Hyoung-Chun</creatorcontrib><creatorcontrib>Rhim, Hyewhon</creatorcontrib><creatorcontrib>Cho, Ik-Hyun</creatorcontrib><creatorcontrib>Nah, Seung-Yeol</creatorcontrib><creatorcontrib>Konkuk University</creatorcontrib><creatorcontrib>eNeuropsychopharmacology and Toxicology Program</creatorcontrib><creatorcontrib>Korea Institute of Science and Technology</creatorcontrib><creatorcontrib>College of Korean Medicine</creatorcontrib><creatorcontrib>College of Pharmacy</creatorcontrib><creatorcontrib>Kyung Hee University</creatorcontrib><creatorcontrib>College of Veterinary Medicine</creatorcontrib><creatorcontrib>cDepartment of Convergence Medical Science</creatorcontrib><creatorcontrib>Korea Institute of Oriental Medicine</creatorcontrib><creatorcontrib>College of Health Sciences</creatorcontrib><creatorcontrib>fCenter for Neuroscience</creatorcontrib><creatorcontrib>aGinsentology Research Laboratory and Department of Physiology</creatorcontrib><creatorcontrib>Kangwon National University</creatorcontrib><creatorcontrib>bMibyeong Research Center</creatorcontrib><creatorcontrib>Sangji University</creatorcontrib><creatorcontrib>dDepartment of Pharmaceutical Engineering</creatorcontrib><title>Effects of Gintonin-Enriched Fraction in an Atopic Dermatitis Animal Model: Involvement of Autotaxin Regulation</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><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.</description><subject>Administration, Oral</subject><subject>Animal models</subject><subject>Animals</subject><subject>anti-atopic dermatitis</subject><subject>Anti-inflammatory agents</subject><subject>Atopic dermatitis</subject><subject>autotaxin</subject><subject>Case-Control Studies</subject><subject>Dermatitis</subject><subject>Dermatitis, Atopic - chemically induced</subject><subject>Dermatitis, Atopic - drug therapy</subject><subject>Dermatitis, Atopic - metabolism</subject><subject>Dinitrofluorobenzene</subject><subject>Dinitrofluorobenzene - administration & dosage</subject><subject>Disease Models, Animal</subject><subject>Ear</subject><subject>Eczema</subject><subject>Ginseng</subject><subject>gintonin</subject><subject>Histamine</subject><subject>Immunoglobulin E</subject><subject>Inflammation</subject><subject>Interferon</subject><subject>Interleukin 4</subject><subject>Leukocytes (eosinophilic)</subject><subject>Lysophosphatidic acid</subject><subject>Male</subject><subject>Mice</subject><subject>Molecular modelling</subject><subject>Oral administration</subject><subject>Panax ginseng</subject><subject>Phosphoric Diester Hydrolases - blood</subject><subject>Plant Extracts - administration & 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 & 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 & dosage</topic><topic>Plant Extracts - therapeutic use</topic><topic>Rodents</topic><topic>Serum levels</topic><topic>Skin</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Byung-Hwan</creatorcontrib><creatorcontrib>Kim, Ho-Kyoung</creatorcontrib><creatorcontrib>Jang, Minhee</creatorcontrib><creatorcontrib>Kim, Hyeon-Joong</creatorcontrib><creatorcontrib>Choi, Sun-Hye</creatorcontrib><creatorcontrib>Hwang, Sung-Hee</creatorcontrib><creatorcontrib>Kim, Hyoung-Chun</creatorcontrib><creatorcontrib>Rhim, Hyewhon</creatorcontrib><creatorcontrib>Cho, Ik-Hyun</creatorcontrib><creatorcontrib>Nah, Seung-Yeol</creatorcontrib><creatorcontrib>Konkuk University</creatorcontrib><creatorcontrib>eNeuropsychopharmacology and Toxicology Program</creatorcontrib><creatorcontrib>Korea Institute of Science and Technology</creatorcontrib><creatorcontrib>College of Korean Medicine</creatorcontrib><creatorcontrib>College of Pharmacy</creatorcontrib><creatorcontrib>Kyung Hee University</creatorcontrib><creatorcontrib>College of Veterinary Medicine</creatorcontrib><creatorcontrib>cDepartment of Convergence Medical Science</creatorcontrib><creatorcontrib>Korea Institute of Oriental Medicine</creatorcontrib><creatorcontrib>College of Health Sciences</creatorcontrib><creatorcontrib>fCenter for Neuroscience</creatorcontrib><creatorcontrib>aGinsentology Research Laboratory and Department of Physiology</creatorcontrib><creatorcontrib>Kangwon National University</creatorcontrib><creatorcontrib>bMibyeong Research Center</creatorcontrib><creatorcontrib>Sangji University</creatorcontrib><creatorcontrib>dDepartment of Pharmaceutical Engineering</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - 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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. 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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