Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy
In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating t...
Gespeichert in:
| Veröffentlicht in: | PloS one 2013-12, Vol.8 (12), p.e81634 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 12 |
| container_start_page | e81634 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Orellana-Paucar, Adriana Monserrath Afrikanova, Tatiana Thomas, Joice Aibuldinov, Yelaman K Dehaen, Wim de Witte, Peter A M Esguerra, Camila V |
| description | In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application. |
| doi_str_mv | 10.1371/journal.pone.0081634 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1467912166</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A478298038</galeid><doaj_id>oai_doaj_org_article_1213b325c15d4be3bc4e47acd0b436e8</doaj_id><sourcerecordid>A478298038</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-5f990bfbaa7bfdf29f03863b1e2e3e375a105c43103246a2e590d6368cae1ba3</originalsourceid><addsrcrecordid>eNqNk12L1DAUhoso7rr6D0QDguDFjEmTft0Iy-LHwMKCLt6G0_Skk6FtxiRdHP-Ef9nMTHeZgoIU2tA-75tz3vQkyUtGl4wX7P3Gjm6Abrm1Ay4pLVnOxaPknFU8XeQp5Y9P1mfJM-83lGa8zPOnyVkquKgYZefJ79XgTbsOnmhne_ILawfa-DWBoSG9HT3Ge4OdJ3YgYY0EVDB3JuwOgAeNcWk1AbcIo-vRxWoIeAJkawMOwUBHGje2REXeNBCQaOsOTsEhhD4yez1uTYdbv3uePNHQeXwxPS-S208fb6--LK5vPq-uLq8XqsjKsMh0VdFa1wBFrRudVprG1njNMEWOvMiA0UwJzihPRQ4pZhVtcp6XCpDVwC-S10fbbWe9nKL0kom8qFjK8jwSqyPRWNjIrTM9uJ20YOThhXWtBBeM6lBGAa95mimWNaJGXiuBogDV0FrwHMvo9WHabax7bFTs2UE3M51_GcxatvZOxp5SUe4N3kwGzv4Y0Yd_lDxRLcSqzKBtNFO98UpeiqJMqzKGFKnlX6h4NdgbFY9Px5OYC97NBJEJ-DO0MHovV9--_j97833Ovj1h1whdWHvbjcHYwc9BcQSVs9471A_JMSr3s3CfhtzPgpxmIcpenab-ILr_-fkf5hMG8g</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1467912166</pqid></control><display><type>article</type><title>Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Orellana-Paucar, Adriana Monserrath ; Afrikanova, Tatiana ; Thomas, Joice ; Aibuldinov, Yelaman K ; Dehaen, Wim ; de Witte, Peter A M ; Esguerra, Camila V</creator><creatorcontrib>Orellana-Paucar, Adriana Monserrath ; Afrikanova, Tatiana ; Thomas, Joice ; Aibuldinov, Yelaman K ; Dehaen, Wim ; de Witte, Peter A M ; Esguerra, Camila V</creatorcontrib><description>In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0081634</identifier><identifier>PMID: 24349101</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animal models ; Animals ; Anticonvulsants ; Anticonvulsants - pharmacokinetics ; Anticonvulsants - pharmacology ; Balance ; Behavior, Animal - drug effects ; Binding sites ; Bioavailability ; Blood-Brain Barrier ; Brain ; Brain - drug effects ; Brain - metabolism ; Brain - physiopathology ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - genetics ; Brain-Derived Neurotrophic Factor - metabolism ; c-Fos protein ; Cancer therapies ; Chemistry ; Disease Models, Animal ; Drug therapy ; Epilepsy ; Evaluation ; Fos protein ; Gene expression ; Gene Expression Regulation - drug effects ; Hypoxia ; Injections, Intraperitoneal ; Ketones - pharmacokinetics ; Ketones - pharmacology ; Laboratories ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity - drug effects ; Neurotoxicity ; Pentylenetetrazole ; Pharmaceuticals ; Postural Balance - drug effects ; Properties (attributes) ; Proto-Oncogene Proteins c-fos - genetics ; Proto-Oncogene Proteins c-fos - metabolism ; Rodents ; Seizing ; Seizures ; Seizures (Medicine) ; Seizures - chemically induced ; Seizures - drug therapy ; Seizures - metabolism ; Seizures - physiopathology ; Sesquiterpenes ; Sesquiterpenes - pharmacokinetics ; Sesquiterpenes - pharmacology ; Sesquiterpenoids ; Studies ; Toxicity ; Walking ; Zebrafish</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e81634</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Orellana-Paucar 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>2013 Orellana-Paucar et al 2013 Orellana-Paucar et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-5f990bfbaa7bfdf29f03863b1e2e3e375a105c43103246a2e590d6368cae1ba3</citedby><cites>FETCH-LOGICAL-c758t-5f990bfbaa7bfdf29f03863b1e2e3e375a105c43103246a2e590d6368cae1ba3</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/PMC3862488/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862488/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24349101$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Orellana-Paucar, Adriana Monserrath</creatorcontrib><creatorcontrib>Afrikanova, Tatiana</creatorcontrib><creatorcontrib>Thomas, Joice</creatorcontrib><creatorcontrib>Aibuldinov, Yelaman K</creatorcontrib><creatorcontrib>Dehaen, Wim</creatorcontrib><creatorcontrib>de Witte, Peter A M</creatorcontrib><creatorcontrib>Esguerra, Camila V</creatorcontrib><title>Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.</description><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anticonvulsants</subject><subject>Anticonvulsants - pharmacokinetics</subject><subject>Anticonvulsants - pharmacology</subject><subject>Balance</subject><subject>Behavior, Animal - drug effects</subject><subject>Binding sites</subject><subject>Bioavailability</subject><subject>Blood-Brain Barrier</subject><subject>Brain</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Brain - physiopathology</subject><subject>Brain-derived neurotrophic factor</subject><subject>Brain-Derived Neurotrophic Factor - genetics</subject><subject>Brain-Derived Neurotrophic Factor - metabolism</subject><subject>c-Fos protein</subject><subject>Cancer therapies</subject><subject>Chemistry</subject><subject>Disease Models, Animal</subject><subject>Drug therapy</subject><subject>Epilepsy</subject><subject>Evaluation</subject><subject>Fos protein</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Hypoxia</subject><subject>Injections, Intraperitoneal</subject><subject>Ketones - pharmacokinetics</subject><subject>Ketones - pharmacology</subject><subject>Laboratories</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Motor Activity - drug effects</subject><subject>Neurotoxicity</subject><subject>Pentylenetetrazole</subject><subject>Pharmaceuticals</subject><subject>Postural Balance - drug effects</subject><subject>Properties (attributes)</subject><subject>Proto-Oncogene Proteins c-fos - genetics</subject><subject>Proto-Oncogene Proteins c-fos - metabolism</subject><subject>Rodents</subject><subject>Seizing</subject><subject>Seizures</subject><subject>Seizures (Medicine)</subject><subject>Seizures - chemically induced</subject><subject>Seizures - drug therapy</subject><subject>Seizures - metabolism</subject><subject>Seizures - physiopathology</subject><subject>Sesquiterpenes</subject><subject>Sesquiterpenes - pharmacokinetics</subject><subject>Sesquiterpenes - pharmacology</subject><subject>Sesquiterpenoids</subject><subject>Studies</subject><subject>Toxicity</subject><subject>Walking</subject><subject>Zebrafish</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>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QDguDFjEmTft0Iy-LHwMKCLt6G0_Skk6FtxiRdHP-Ef9nMTHeZgoIU2tA-75tz3vQkyUtGl4wX7P3Gjm6Abrm1Ay4pLVnOxaPknFU8XeQp5Y9P1mfJM-83lGa8zPOnyVkquKgYZefJ79XgTbsOnmhne_ILawfa-DWBoSG9HT3Ge4OdJ3YgYY0EVDB3JuwOgAeNcWk1AbcIo-vRxWoIeAJkawMOwUBHGje2REXeNBCQaOsOTsEhhD4yez1uTYdbv3uePNHQeXwxPS-S208fb6--LK5vPq-uLq8XqsjKsMh0VdFa1wBFrRudVprG1njNMEWOvMiA0UwJzihPRQ4pZhVtcp6XCpDVwC-S10fbbWe9nKL0kom8qFjK8jwSqyPRWNjIrTM9uJ20YOThhXWtBBeM6lBGAa95mimWNaJGXiuBogDV0FrwHMvo9WHabax7bFTs2UE3M51_GcxatvZOxp5SUe4N3kwGzv4Y0Yd_lDxRLcSqzKBtNFO98UpeiqJMqzKGFKnlX6h4NdgbFY9Px5OYC97NBJEJ-DO0MHovV9--_j97833Ovj1h1whdWHvbjcHYwc9BcQSVs9471A_JMSr3s3CfhtzPgpxmIcpenab-ILr_-fkf5hMG8g</recordid><startdate>20131213</startdate><enddate>20131213</enddate><creator>Orellana-Paucar, Adriana Monserrath</creator><creator>Afrikanova, Tatiana</creator><creator>Thomas, Joice</creator><creator>Aibuldinov, Yelaman K</creator><creator>Dehaen, Wim</creator><creator>de Witte, Peter A M</creator><creator>Esguerra, Camila V</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>IOV</scope><scope>ISR</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>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131213</creationdate><title>Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy</title><author>Orellana-Paucar, Adriana Monserrath ; Afrikanova, Tatiana ; Thomas, Joice ; Aibuldinov, Yelaman K ; Dehaen, Wim ; de Witte, Peter A M ; Esguerra, Camila V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-5f990bfbaa7bfdf29f03863b1e2e3e375a105c43103246a2e590d6368cae1ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Anticonvulsants</topic><topic>Anticonvulsants - pharmacokinetics</topic><topic>Anticonvulsants - pharmacology</topic><topic>Balance</topic><topic>Behavior, Animal - drug effects</topic><topic>Binding sites</topic><topic>Bioavailability</topic><topic>Blood-Brain Barrier</topic><topic>Brain</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Brain - physiopathology</topic><topic>Brain-derived neurotrophic factor</topic><topic>Brain-Derived Neurotrophic Factor - genetics</topic><topic>Brain-Derived Neurotrophic Factor - metabolism</topic><topic>c-Fos protein</topic><topic>Cancer therapies</topic><topic>Chemistry</topic><topic>Disease Models, Animal</topic><topic>Drug therapy</topic><topic>Epilepsy</topic><topic>Evaluation</topic><topic>Fos protein</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Hypoxia</topic><topic>Injections, Intraperitoneal</topic><topic>Ketones - pharmacokinetics</topic><topic>Ketones - pharmacology</topic><topic>Laboratories</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Motor Activity - drug effects</topic><topic>Neurotoxicity</topic><topic>Pentylenetetrazole</topic><topic>Pharmaceuticals</topic><topic>Postural Balance - drug effects</topic><topic>Properties (attributes)</topic><topic>Proto-Oncogene Proteins c-fos - genetics</topic><topic>Proto-Oncogene Proteins c-fos - metabolism</topic><topic>Rodents</topic><topic>Seizing</topic><topic>Seizures</topic><topic>Seizures (Medicine)</topic><topic>Seizures - chemically induced</topic><topic>Seizures - drug therapy</topic><topic>Seizures - metabolism</topic><topic>Seizures - physiopathology</topic><topic>Sesquiterpenes</topic><topic>Sesquiterpenes - pharmacokinetics</topic><topic>Sesquiterpenes - pharmacology</topic><topic>Sesquiterpenoids</topic><topic>Studies</topic><topic>Toxicity</topic><topic>Walking</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Orellana-Paucar, Adriana Monserrath</creatorcontrib><creatorcontrib>Afrikanova, Tatiana</creatorcontrib><creatorcontrib>Thomas, Joice</creatorcontrib><creatorcontrib>Aibuldinov, Yelaman K</creatorcontrib><creatorcontrib>Dehaen, Wim</creatorcontrib><creatorcontrib>de Witte, Peter A M</creatorcontrib><creatorcontrib>Esguerra, Camila V</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</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 One Sustainability</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 - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</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>Orellana-Paucar, Adriana Monserrath</au><au>Afrikanova, Tatiana</au><au>Thomas, Joice</au><au>Aibuldinov, Yelaman K</au><au>Dehaen, Wim</au><au>de Witte, Peter A M</au><au>Esguerra, Camila V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-12-13</date><risdate>2013</risdate><volume>8</volume><issue>12</issue><spage>e81634</spage><pages>e81634-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24349101</pmid><doi>10.1371/journal.pone.0081634</doi><tpages>e81634</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-12, Vol.8 (12), p.e81634 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1467912166 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Analysis Animal models Animals Anticonvulsants Anticonvulsants - pharmacokinetics Anticonvulsants - pharmacology Balance Behavior, Animal - drug effects Binding sites Bioavailability Blood-Brain Barrier Brain Brain - drug effects Brain - metabolism Brain - physiopathology Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - genetics Brain-Derived Neurotrophic Factor - metabolism c-Fos protein Cancer therapies Chemistry Disease Models, Animal Drug therapy Epilepsy Evaluation Fos protein Gene expression Gene Expression Regulation - drug effects Hypoxia Injections, Intraperitoneal Ketones - pharmacokinetics Ketones - pharmacology Laboratories Male Mice Mice, Inbred C57BL Motor Activity - drug effects Neurotoxicity Pentylenetetrazole Pharmaceuticals Postural Balance - drug effects Properties (attributes) Proto-Oncogene Proteins c-fos - genetics Proto-Oncogene Proteins c-fos - metabolism Rodents Seizing Seizures Seizures (Medicine) Seizures - chemically induced Seizures - drug therapy Seizures - metabolism Seizures - physiopathology Sesquiterpenes Sesquiterpenes - pharmacokinetics Sesquiterpenes - pharmacology Sesquiterpenoids Studies Toxicity Walking Zebrafish |
| title | Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T18%3A42%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Insights%20from%20zebrafish%20and%20mouse%20models%20on%20the%20activity%20and%20safety%20of%20ar-turmerone%20as%20a%20potential%20drug%20candidate%20for%20the%20treatment%20of%20epilepsy&rft.jtitle=PloS%20one&rft.au=Orellana-Paucar,%20Adriana%20Monserrath&rft.date=2013-12-13&rft.volume=8&rft.issue=12&rft.spage=e81634&rft.pages=e81634-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0081634&rft_dat=%3Cgale_plos_%3EA478298038%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1467912166&rft_id=info:pmid/24349101&rft_galeid=A478298038&rft_doaj_id=oai_doaj_org_article_1213b325c15d4be3bc4e47acd0b436e8&rfr_iscdi=true |