Specific binding and characteristics of 18β-glycyrrhetinic acid in rat brain
18β-Glycyrrhetinic acid (GA) is the aglycone of glycyrrhizin that is a component of Glycyrrhiza, and has several pharmacological actions in the central nervous system. Recently, GA has been demonstrated to reach the brain by crossing the blood-brain barrier in rats after oral administration of a Gly...
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| description | 18β-Glycyrrhetinic acid (GA) is the aglycone of glycyrrhizin that is a component of Glycyrrhiza, and has several pharmacological actions in the central nervous system. Recently, GA has been demonstrated to reach the brain by crossing the blood-brain barrier in rats after oral administration of a Glycyrrhiza-containing traditional Japanese medicine, yokukansan. These findings suggest that there are specific binding sites for GA in the brain. Here we show evidence that [3H]GA binds specifically to several brain areas by quantitative autoradiography; the density was higher in the hippocampus, moderate in the caudate putamen, nucleus accumbens, amygdala, olfactory bulb, cerebral cortex, thalamus, and mid brain, and lower in the brain stem and cerebellum. Several kinds of steroids, gap junction-blocking reagents, glutamate transporter-recognized compounds, and glutamate receptor agonists did not inhibit the [3H]GA binding. Microautoradiography showed that the [3H]GA signals in the hippocampus were distributed in small non-neuronal cells similar to astrocytes. Immunohistochemical analysis revealed that immunoreactivity of 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), a defined molecule recognized by GA, was detected mainly in neurons, moderately in astrocytes, and very slightly in microglial cells, of the hippocampus. These results demonstrate that specific binding sites for GA exist in rat brain tissue, and suggest that the pharmacological actions of GA may be related to 11β-HSD1 in astrocytes. This finding provides important information to understand the pharmacology of GA in the brain. |
| doi_str_mv | 10.1371/journal.pone.0095760 |
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Recently, GA has been demonstrated to reach the brain by crossing the blood-brain barrier in rats after oral administration of a Glycyrrhiza-containing traditional Japanese medicine, yokukansan. These findings suggest that there are specific binding sites for GA in the brain. Here we show evidence that [3H]GA binds specifically to several brain areas by quantitative autoradiography; the density was higher in the hippocampus, moderate in the caudate putamen, nucleus accumbens, amygdala, olfactory bulb, cerebral cortex, thalamus, and mid brain, and lower in the brain stem and cerebellum. Several kinds of steroids, gap junction-blocking reagents, glutamate transporter-recognized compounds, and glutamate receptor agonists did not inhibit the [3H]GA binding. Microautoradiography showed that the [3H]GA signals in the hippocampus were distributed in small non-neuronal cells similar to astrocytes. Immunohistochemical analysis revealed that immunoreactivity of 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), a defined molecule recognized by GA, was detected mainly in neurons, moderately in astrocytes, and very slightly in microglial cells, of the hippocampus. These results demonstrate that specific binding sites for GA exist in rat brain tissue, and suggest that the pharmacological actions of GA may be related to 11β-HSD1 in astrocytes. This finding provides important information to understand the pharmacology of GA in the brain.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0095760</identifier><identifier>PMID: 24752617</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>11-beta-Hydroxysteroid Dehydrogenase Type 1 - metabolism ; 11β-Hydroxysteroid dehydrogenase ; Acids ; Aggressiveness ; Aging ; Alzheimer's disease ; Amygdala ; Animals ; Astrocytes ; Astrocytes - metabolism ; Autoradiography ; Binding sites ; Biology and Life Sciences ; Blood-brain barrier ; Brain - metabolism ; Brain research ; Brain stem ; Central nervous system ; Cerebellum ; Cerebral cortex ; Cortex (olfactory) ; Dehydrogenases ; Dementia ; Gene expression ; Glutamic acid receptors ; Glutamic acid transporter ; Glycyrrhetinic Acid - analogs & derivatives ; Glycyrrhetinic Acid - metabolism ; Glycyrrhiza ; Glycyrrhizin ; Hippocampus ; Hippocampus - metabolism ; Immunohistochemistry ; Immunoreactivity ; Ischemia ; Laboratory animals ; Medical research ; Medicine ; Medicine and Health Sciences ; Memory ; Microglia - metabolism ; Microglial cells ; Neurons - metabolism ; Neurosciences ; Neurotoxicity ; Nucleus accumbens ; Olfactory bulb ; Oral administration ; Oxidative stress ; Pharmacology ; Proteins ; Putamen ; Rats ; Reagents ; Research and Analysis Methods ; Rodents ; Steroid hormones ; Steroids ; Thalamus</subject><ispartof>PloS one, 2014-04, Vol.9 (4), p.e95760-e95760</ispartof><rights>2014 Mizoguchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://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>2014 Mizoguchi et al 2014 Mizoguchi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-a60214d0a058bfc975e6fa27963b3119fedaf408a7abe61ea9e98e2d169fba593</citedby><cites>FETCH-LOGICAL-c526t-a60214d0a058bfc975e6fa27963b3119fedaf408a7abe61ea9e98e2d169fba593</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/PMC3994142/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994142/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24752617$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Coles, Jonathan A.</contributor><creatorcontrib>Mizoguchi, Kazushige</creatorcontrib><creatorcontrib>Kanno, Hitomi</creatorcontrib><creatorcontrib>Ikarashi, Yasushi</creatorcontrib><creatorcontrib>Kase, Yoshio</creatorcontrib><title>Specific binding and characteristics of 18β-glycyrrhetinic acid in rat brain</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>18β-Glycyrrhetinic acid (GA) is the aglycone of glycyrrhizin that is a component of Glycyrrhiza, and has several pharmacological actions in the central nervous system. Recently, GA has been demonstrated to reach the brain by crossing the blood-brain barrier in rats after oral administration of a Glycyrrhiza-containing traditional Japanese medicine, yokukansan. These findings suggest that there are specific binding sites for GA in the brain. Here we show evidence that [3H]GA binds specifically to several brain areas by quantitative autoradiography; the density was higher in the hippocampus, moderate in the caudate putamen, nucleus accumbens, amygdala, olfactory bulb, cerebral cortex, thalamus, and mid brain, and lower in the brain stem and cerebellum. Several kinds of steroids, gap junction-blocking reagents, glutamate transporter-recognized compounds, and glutamate receptor agonists did not inhibit the [3H]GA binding. Microautoradiography showed that the [3H]GA signals in the hippocampus were distributed in small non-neuronal cells similar to astrocytes. Immunohistochemical analysis revealed that immunoreactivity of 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), a defined molecule recognized by GA, was detected mainly in neurons, moderately in astrocytes, and very slightly in microglial cells, of the hippocampus. These results demonstrate that specific binding sites for GA exist in rat brain tissue, and suggest that the pharmacological actions of GA may be related to 11β-HSD1 in astrocytes. This finding provides important information to understand the pharmacology of GA in the brain.</description><subject>11-beta-Hydroxysteroid Dehydrogenase Type 1 - metabolism</subject><subject>11β-Hydroxysteroid dehydrogenase</subject><subject>Acids</subject><subject>Aggressiveness</subject><subject>Aging</subject><subject>Alzheimer's disease</subject><subject>Amygdala</subject><subject>Animals</subject><subject>Astrocytes</subject><subject>Astrocytes - metabolism</subject><subject>Autoradiography</subject><subject>Binding sites</subject><subject>Biology and Life Sciences</subject><subject>Blood-brain barrier</subject><subject>Brain - metabolism</subject><subject>Brain research</subject><subject>Brain stem</subject><subject>Central nervous system</subject><subject>Cerebellum</subject><subject>Cerebral cortex</subject><subject>Cortex (olfactory)</subject><subject>Dehydrogenases</subject><subject>Dementia</subject><subject>Gene expression</subject><subject>Glutamic acid receptors</subject><subject>Glutamic acid transporter</subject><subject>Glycyrrhetinic Acid - analogs & derivatives</subject><subject>Glycyrrhetinic Acid - metabolism</subject><subject>Glycyrrhiza</subject><subject>Glycyrrhizin</subject><subject>Hippocampus</subject><subject>Hippocampus - metabolism</subject><subject>Immunohistochemistry</subject><subject>Immunoreactivity</subject><subject>Ischemia</subject><subject>Laboratory animals</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Memory</subject><subject>Microglia - metabolism</subject><subject>Microglial cells</subject><subject>Neurons - metabolism</subject><subject>Neurosciences</subject><subject>Neurotoxicity</subject><subject>Nucleus accumbens</subject><subject>Olfactory bulb</subject><subject>Oral administration</subject><subject>Oxidative stress</subject><subject>Pharmacology</subject><subject>Proteins</subject><subject>Putamen</subject><subject>Rats</subject><subject>Reagents</subject><subject>Research and Analysis Methods</subject><subject>Rodents</subject><subject>Steroid hormones</subject><subject>Steroids</subject><subject>Thalamus</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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>eNptUs1uEzEYtBCIlsAbIFiJC5cE_6y96wsSqvipVMQBOFuf7W8TRxs72BukvBYPwjPhkm3VIk627Jn5Zuwh5DmjKyY69mabDjnCuNqniCtKtewUfUDOmRZ8qTgVD-_sz8iTUraUStEr9Zic8baTXLHunHz-ukcXhuAaG6IPcd1A9I3bQAY3YQ5lCq40aWhY__vXcj0e3THnDU4hVgq44JsQmwxTYzOE-JQ8GmAs-GxeF-T7h_ffLj4tr758vLx4d7V0dey0BEU5az0FKns7ON1JVAPwTithBWN6QA9DS3vowKJiCBp1j9wzpQcLUosFeXnS3Y-pmPklimGS9VR3QrYVcXlC-ARbs89hB_loEgTz9yDltYFcs41ooLWVJi14D9UUagcCnNeInFpph6r1dp52sDv0DuOUYbwnev8mho1Zp59GaN2ylleB17NATj8OWCazC8XhOELEdDj5rt_Eq_UFefUP9P_p2hPK5VRKxuHWDKPmuh03LHPdDjO3o9Je3A1yS7qpg_gDj0C6ag</recordid><startdate>20140421</startdate><enddate>20140421</enddate><creator>Mizoguchi, Kazushige</creator><creator>Kanno, Hitomi</creator><creator>Ikarashi, Yasushi</creator><creator>Kase, Yoshio</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>AEUYN</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>20140421</creationdate><title>Specific binding and characteristics of 18β-glycyrrhetinic acid in rat brain</title><author>Mizoguchi, Kazushige ; Kanno, Hitomi ; Ikarashi, Yasushi ; Kase, Yoshio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-a60214d0a058bfc975e6fa27963b3119fedaf408a7abe61ea9e98e2d169fba593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>11-beta-Hydroxysteroid Dehydrogenase Type 1 - metabolism</topic><topic>11β-Hydroxysteroid dehydrogenase</topic><topic>Acids</topic><topic>Aggressiveness</topic><topic>Aging</topic><topic>Alzheimer's disease</topic><topic>Amygdala</topic><topic>Animals</topic><topic>Astrocytes</topic><topic>Astrocytes - metabolism</topic><topic>Autoradiography</topic><topic>Binding sites</topic><topic>Biology and Life Sciences</topic><topic>Blood-brain barrier</topic><topic>Brain - metabolism</topic><topic>Brain research</topic><topic>Brain stem</topic><topic>Central nervous system</topic><topic>Cerebellum</topic><topic>Cerebral cortex</topic><topic>Cortex (olfactory)</topic><topic>Dehydrogenases</topic><topic>Dementia</topic><topic>Gene expression</topic><topic>Glutamic acid receptors</topic><topic>Glutamic acid transporter</topic><topic>Glycyrrhetinic Acid - analogs & derivatives</topic><topic>Glycyrrhetinic Acid - metabolism</topic><topic>Glycyrrhiza</topic><topic>Glycyrrhizin</topic><topic>Hippocampus</topic><topic>Hippocampus - metabolism</topic><topic>Immunohistochemistry</topic><topic>Immunoreactivity</topic><topic>Ischemia</topic><topic>Laboratory animals</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Memory</topic><topic>Microglia - 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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>Mizoguchi, Kazushige</au><au>Kanno, Hitomi</au><au>Ikarashi, Yasushi</au><au>Kase, Yoshio</au><au>Coles, Jonathan A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Specific binding and characteristics of 18β-glycyrrhetinic acid in rat brain</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-04-21</date><risdate>2014</risdate><volume>9</volume><issue>4</issue><spage>e95760</spage><epage>e95760</epage><pages>e95760-e95760</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>18β-Glycyrrhetinic acid (GA) is the aglycone of glycyrrhizin that is a component of Glycyrrhiza, and has several pharmacological actions in the central nervous system. Recently, GA has been demonstrated to reach the brain by crossing the blood-brain barrier in rats after oral administration of a Glycyrrhiza-containing traditional Japanese medicine, yokukansan. These findings suggest that there are specific binding sites for GA in the brain. Here we show evidence that [3H]GA binds specifically to several brain areas by quantitative autoradiography; the density was higher in the hippocampus, moderate in the caudate putamen, nucleus accumbens, amygdala, olfactory bulb, cerebral cortex, thalamus, and mid brain, and lower in the brain stem and cerebellum. Several kinds of steroids, gap junction-blocking reagents, glutamate transporter-recognized compounds, and glutamate receptor agonists did not inhibit the [3H]GA binding. Microautoradiography showed that the [3H]GA signals in the hippocampus were distributed in small non-neuronal cells similar to astrocytes. Immunohistochemical analysis revealed that immunoreactivity of 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), a defined molecule recognized by GA, was detected mainly in neurons, moderately in astrocytes, and very slightly in microglial cells, of the hippocampus. These results demonstrate that specific binding sites for GA exist in rat brain tissue, and suggest that the pharmacological actions of GA may be related to 11β-HSD1 in astrocytes. This finding provides important information to understand the pharmacology of GA in the brain.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24752617</pmid><doi>10.1371/journal.pone.0095760</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 11-beta-Hydroxysteroid Dehydrogenase Type 1 - metabolism 11β-Hydroxysteroid dehydrogenase Acids Aggressiveness Aging Alzheimer's disease Amygdala Animals Astrocytes Astrocytes - metabolism Autoradiography Binding sites Biology and Life Sciences Blood-brain barrier Brain - metabolism Brain research Brain stem Central nervous system Cerebellum Cerebral cortex Cortex (olfactory) Dehydrogenases Dementia Gene expression Glutamic acid receptors Glutamic acid transporter Glycyrrhetinic Acid - analogs & derivatives Glycyrrhetinic Acid - metabolism Glycyrrhiza Glycyrrhizin Hippocampus Hippocampus - metabolism Immunohistochemistry Immunoreactivity Ischemia Laboratory animals Medical research Medicine Medicine and Health Sciences Memory Microglia - metabolism Microglial cells Neurons - metabolism Neurosciences Neurotoxicity Nucleus accumbens Olfactory bulb Oral administration Oxidative stress Pharmacology Proteins Putamen Rats Reagents Research and Analysis Methods Rodents Steroid hormones Steroids Thalamus |
| title | Specific binding and characteristics of 18β-glycyrrhetinic acid in rat brain |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T00%3A37%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Specific%20binding%20and%20characteristics%20of%2018%CE%B2-glycyrrhetinic%20acid%20in%20rat%20brain&rft.jtitle=PloS%20one&rft.au=Mizoguchi,%20Kazushige&rft.date=2014-04-21&rft.volume=9&rft.issue=4&rft.spage=e95760&rft.epage=e95760&rft.pages=e95760-e95760&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0095760&rft_dat=%3Cproquest_plos_%3E1518620297%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1518097354&rft_id=info:pmid/24752617&rft_doaj_id=oai_doaj_org_article_a4b1805badda4d0e9ca3acd9ee20b5bf&rfr_iscdi=true |