An estrogen receptor dependent mechanism of Oroxylin A in the repression of inflammatory response
Oroxylin A, a natural flavonoid, is one of the main bioactive compounds that underlie the anti-inflammatory effect of the medicinal herb Scutellaria baicalensis Georgi widely used in southeastern Asia; however, the molecular mechanisms for the therapeutic benefits remain largely unclear. In this stu...
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description | Oroxylin A, a natural flavonoid, is one of the main bioactive compounds that underlie the anti-inflammatory effect of the medicinal herb Scutellaria baicalensis Georgi widely used in southeastern Asia; however, the molecular mechanisms for the therapeutic benefits remain largely unclear. In this study, we found that Oroxylin A induces estrogen-responsive gene expression and promoter activity. In macrophages, Oroxylin A treatment significantly attenuates lipopolysaccharide (LPS)-induced but not basal inflammatory response, including nitric oxide (NO) production and the expression of inflammatory mediators (i.e., iNOS and COX-2) and cytokines (i.e., TNF-α, IL-1β, and IL-6), in an estrogen receptor (ER)-dependent manner. Oroxylin A treatment also dramatically decreases LPS-induced secretion of pro-inflammatory cytokines. Furthermore, the downregulation of all these inflammatory parameters by Oroxylin A was abolished when cells were pretreated with specific ER antagonist. Thus, Oroxylin A is a novel phytoestrogen and exhibits anti-inflammatory effects that are mediated by ER activity. |
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In this study, we found that Oroxylin A induces estrogen-responsive gene expression and promoter activity. In macrophages, Oroxylin A treatment significantly attenuates lipopolysaccharide (LPS)-induced but not basal inflammatory response, including nitric oxide (NO) production and the expression of inflammatory mediators (i.e., iNOS and COX-2) and cytokines (i.e., TNF-α, IL-1β, and IL-6), in an estrogen receptor (ER)-dependent manner. Oroxylin A treatment also dramatically decreases LPS-induced secretion of pro-inflammatory cytokines. Furthermore, the downregulation of all these inflammatory parameters by Oroxylin A was abolished when cells were pretreated with specific ER antagonist. Thus, Oroxylin A is a novel phytoestrogen and exhibits anti-inflammatory effects that are mediated by ER activity.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0069555</identifier><identifier>PMID: 23922737</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Bioactive compounds ; Biological products ; Cell culture ; Cell Line ; Cell Line, Tumor ; Chinese medicine ; Cyclooxygenase-2 ; Cytokines ; Education ; Endocrinology ; Enzyme-Linked Immunosorbent Assay ; Estrogen Receptor alpha - metabolism ; Estrogen Receptor beta - metabolism ; Estrogen receptors ; Estrogens ; Flavonoids ; Flavonoids - pharmacology ; Gene expression ; HeLa Cells ; Herbal medicine ; Humans ; Inflammation ; Inflammation - metabolism ; Inflammatory response ; Interleukin 6 ; Laboratories ; Lipopolysaccharides ; Macrophages ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - metabolism ; Mice ; Molecular modelling ; Nitric oxide ; Nitric Oxide - metabolism ; Nitric-oxide synthase ; Pharmacology ; Plasmids ; Reverse Transcriptase Polymerase Chain Reaction ; Rodents ; Smooth muscle ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e69555-e69555</ispartof><rights>2013 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Wang et al 2013 Wang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c475t-d8d31d261f061d27df2e9805cdea5ba5b57fc0fe361a927b3a47196034fc63ba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726624/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726624/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23922737$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Qin, Gangjian</contributor><creatorcontrib>Wang, Hong</creatorcontrib><creatorcontrib>Guo, Ying</creatorcontrib><creatorcontrib>Zhao, Xin</creatorcontrib><creatorcontrib>Li, Huiying</creatorcontrib><creatorcontrib>Fan, Guanwei</creatorcontrib><creatorcontrib>Mao, Haoping</creatorcontrib><creatorcontrib>Miao, Lin</creatorcontrib><creatorcontrib>Gao, Xiumei</creatorcontrib><title>An estrogen receptor dependent mechanism of Oroxylin A in the repression of inflammatory response</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Oroxylin A, a natural flavonoid, is one of the main bioactive compounds that underlie the anti-inflammatory effect of the medicinal herb Scutellaria baicalensis Georgi widely used in southeastern Asia; however, the molecular mechanisms for the therapeutic benefits remain largely unclear. In this study, we found that Oroxylin A induces estrogen-responsive gene expression and promoter activity. In macrophages, Oroxylin A treatment significantly attenuates lipopolysaccharide (LPS)-induced but not basal inflammatory response, including nitric oxide (NO) production and the expression of inflammatory mediators (i.e., iNOS and COX-2) and cytokines (i.e., TNF-α, IL-1β, and IL-6), in an estrogen receptor (ER)-dependent manner. Oroxylin A treatment also dramatically decreases LPS-induced secretion of pro-inflammatory cytokines. Furthermore, the downregulation of all these inflammatory parameters by Oroxylin A was abolished when cells were pretreated with specific ER antagonist. Thus, Oroxylin A is a novel phytoestrogen and exhibits anti-inflammatory effects that are mediated by ER activity.</description><subject>Animals</subject><subject>Bioactive compounds</subject><subject>Biological products</subject><subject>Cell culture</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Chinese medicine</subject><subject>Cyclooxygenase-2</subject><subject>Cytokines</subject><subject>Education</subject><subject>Endocrinology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Estrogen Receptor beta - metabolism</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Flavonoids</subject><subject>Flavonoids - pharmacology</subject><subject>Gene expression</subject><subject>HeLa Cells</subject><subject>Herbal medicine</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Inflammatory response</subject><subject>Interleukin 6</subject><subject>Laboratories</subject><subject>Lipopolysaccharides</subject><subject>Macrophages</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Molecular modelling</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric-oxide synthase</subject><subject>Pharmacology</subject><subject>Plasmids</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Smooth muscle</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUl1rFDEUHUSxtfoPRAd88WXXfGfyIizFaqHQF30Od5M7u7PMJGMyW9x_b7Y7La0IIQm555z7kVNV7ylZUq7pl13cpwD9cowBl4QoI6V8UZ1Tw9lCMcJfPrmfVW9y3hEieaPU6-qMccOY5vq8glWoMU8pbjDUCR2OU0y1xxGDxzDVA7othC4PdWzr2xT_HPou1Ku6bNMWC2NMmHMXwzHehbaHYYAicSihXErL-LZ61UKf8d18XlS_rr79vPyxuLn9fn25ulk4oeW08I3n1DNFW6LKqX3L0DREOo8g12VJ3TrSIlcUDNNrDkJTowgXrVN8Dfyi-njSHfuY7TydbKkQxBilJCmI6xPCR9jZMXUDpION0Nn7h5g2FtLUuR6tanwDwnHqnBDADEiUriTTyAhD4EXr65xtvx7QuzKrBP0z0eeR0G3tJt5ZrplSTBSBz7NAir_35Qvs0GWHfQ8B4_5YN21UmQw3BfrpH-j_uxMnlEsx54TtYzGU2KNjHlj26Bg7O6bQPjxt5JH0YBH-F0xswJk</recordid><startdate>20130729</startdate><enddate>20130729</enddate><creator>Wang, Hong</creator><creator>Guo, Ying</creator><creator>Zhao, Xin</creator><creator>Li, Huiying</creator><creator>Fan, Guanwei</creator><creator>Mao, Haoping</creator><creator>Miao, Lin</creator><creator>Gao, Xiumei</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130729</creationdate><title>An estrogen receptor dependent mechanism of Oroxylin A in the repression of inflammatory response</title><author>Wang, Hong ; Guo, Ying ; Zhao, Xin ; Li, Huiying ; Fan, Guanwei ; Mao, Haoping ; Miao, Lin ; Gao, Xiumei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-d8d31d261f061d27df2e9805cdea5ba5b57fc0fe361a927b3a47196034fc63ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Bioactive compounds</topic><topic>Biological products</topic><topic>Cell culture</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Chinese medicine</topic><topic>Cyclooxygenase-2</topic><topic>Cytokines</topic><topic>Education</topic><topic>Endocrinology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Estrogen Receptor beta - metabolism</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Flavonoids</topic><topic>Flavonoids - pharmacology</topic><topic>Gene expression</topic><topic>HeLa Cells</topic><topic>Herbal medicine</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation - metabolism</topic><topic>Inflammatory response</topic><topic>Interleukin 6</topic><topic>Laboratories</topic><topic>Lipopolysaccharides</topic><topic>Macrophages</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Macrophages - metabolism</topic><topic>Mice</topic><topic>Molecular modelling</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric-oxide synthase</topic><topic>Pharmacology</topic><topic>Plasmids</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Rodents</topic><topic>Smooth muscle</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Hong</creatorcontrib><creatorcontrib>Guo, Ying</creatorcontrib><creatorcontrib>Zhao, Xin</creatorcontrib><creatorcontrib>Li, Huiying</creatorcontrib><creatorcontrib>Fan, Guanwei</creatorcontrib><creatorcontrib>Mao, Haoping</creatorcontrib><creatorcontrib>Miao, Lin</creatorcontrib><creatorcontrib>Gao, Xiumei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Hong</au><au>Guo, Ying</au><au>Zhao, Xin</au><au>Li, Huiying</au><au>Fan, Guanwei</au><au>Mao, Haoping</au><au>Miao, Lin</au><au>Gao, Xiumei</au><au>Qin, Gangjian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An estrogen receptor dependent mechanism of Oroxylin A in the repression of inflammatory response</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-07-29</date><risdate>2013</risdate><volume>8</volume><issue>7</issue><spage>e69555</spage><epage>e69555</epage><pages>e69555-e69555</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Oroxylin A, a natural flavonoid, is one of the main bioactive compounds that underlie the anti-inflammatory effect of the medicinal herb Scutellaria baicalensis Georgi widely used in southeastern Asia; however, the molecular mechanisms for the therapeutic benefits remain largely unclear. In this study, we found that Oroxylin A induces estrogen-responsive gene expression and promoter activity. In macrophages, Oroxylin A treatment significantly attenuates lipopolysaccharide (LPS)-induced but not basal inflammatory response, including nitric oxide (NO) production and the expression of inflammatory mediators (i.e., iNOS and COX-2) and cytokines (i.e., TNF-α, IL-1β, and IL-6), in an estrogen receptor (ER)-dependent manner. Oroxylin A treatment also dramatically decreases LPS-induced secretion of pro-inflammatory cytokines. Furthermore, the downregulation of all these inflammatory parameters by Oroxylin A was abolished when cells were pretreated with specific ER antagonist. Thus, Oroxylin A is a novel phytoestrogen and exhibits anti-inflammatory effects that are mediated by ER activity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23922737</pmid><doi>10.1371/journal.pone.0069555</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animals Bioactive compounds Biological products Cell culture Cell Line Cell Line, Tumor Chinese medicine Cyclooxygenase-2 Cytokines Education Endocrinology Enzyme-Linked Immunosorbent Assay Estrogen Receptor alpha - metabolism Estrogen Receptor beta - metabolism Estrogen receptors Estrogens Flavonoids Flavonoids - pharmacology Gene expression HeLa Cells Herbal medicine Humans Inflammation Inflammation - metabolism Inflammatory response Interleukin 6 Laboratories Lipopolysaccharides Macrophages Macrophages - drug effects Macrophages - immunology Macrophages - metabolism Mice Molecular modelling Nitric oxide Nitric Oxide - metabolism Nitric-oxide synthase Pharmacology Plasmids Reverse Transcriptase Polymerase Chain Reaction Rodents Smooth muscle Tumor necrosis factor-TNF Tumor necrosis factor-α |
title | An estrogen receptor dependent mechanism of Oroxylin A in the repression of inflammatory response |
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