Insights from Zebrafish and Mouse Models on the Activity and Safety of Ar-Turmerone as a Potential Drug Candidate for the Treatment of Epilepsy
Publication Date
December 13, 2013
Journal
PLOS ONE
Authors
Adriana Monserrath Orellana Paucar, Tatiana Afrikanova, Joice Thomas, Yelaman K. Aibuldinov, et al
Volume
8
Issue
12
Pages
e81634
DOI
https://dx.plos.org/10.1371/journal.pone.0081634
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0081634
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/24349101
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862488
Europe PMC
http://europepmc.org/abstract/MED/24349101
Web of Science
000328734200012
Scopus
84892668173
Mendeley
http://www.mendeley.com/research/insights-zebrafish-mouse-models-activity-safety-arturmerone-potential-drug-candidate-treatment-epile
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Mendeley | Further Information

{"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", "type"=>"journal", "authors"=>[{"first_name"=>"Adriana Monserrath", "last_name"=>"Orellana-Paucar", "scopus_author_id"=>"55159727400"}, {"first_name"=>"Tatiana", "last_name"=>"Afrikanova", "scopus_author_id"=>"54396726100"}, {"first_name"=>"Joice", "last_name"=>"Thomas", "scopus_author_id"=>"9741716100"}, {"first_name"=>"Yelaman K.", "last_name"=>"Aibuldinov", "scopus_author_id"=>"55641119100"}, {"first_name"=>"Wim", "last_name"=>"Dehaen", "scopus_author_id"=>"7005455325"}, {"first_name"=>"Peter A.M.", "last_name"=>"De Witte", "scopus_author_id"=>"7006646483"}, {"first_name"=>"Camila V.", "last_name"=>"Esguerra", "scopus_author_id"=>"6602885945"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (ISSNLinking)", "sgr"=>"84892668173", "pui"=>"372154221", "pmid"=>"24349101", "issn"=>"19326203", "scopus"=>"2-s2.0-84892668173", "doi"=>"10.1371/journal.pone.0081634"}, "id"=>"4764b4ad-99a6-3d16-9a73-a8bbdc4a6925", "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.", "link"=>"http://www.mendeley.com/research/insights-zebrafish-mouse-models-activity-safety-arturmerone-potential-drug-candidate-treatment-epile", "reader_count"=>46, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>4, "Researcher"=>10, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>4, "Student > Master"=>6, "Other"=>3, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>4, "Researcher"=>10, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>4, "Student > Master"=>6, "Other"=>3, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Nursing and Health Professions"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>7, "Agricultural and Biological Sciences"=>14, "Neuroscience"=>7, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Chemistry"=>4, "Computer Science"=>2, "Immunology and Microbiology"=>2, "Linguistics"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>7}, "Chemistry"=>{"Chemistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Computer Science"=>{"Computer Science"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Linguistics"=>{"Linguistics"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "reader_count_by_country"=>{"Russia"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1314777"], "description"=>"<p>Ar-turmerone (AT) downregulated PTZ-induced <i>c-fos</i> expression and upregulated <i>bdnf</i> expression in the abscense of PTZ treatment. Statistically significant differences between groups: control (VHC), vehicle treated exposed to PTZ (PTZ), ar-turmerone treated (AT) and ar-turmerone treated exposed to PTZ (AT+PTZ) are labeled as * for p < 0.05 and ** for p < 0.001 (one-way ANOVA test).</p>", "links"=>[], "tags"=>["ar-turmerone", "seizure-related", "zebrafish"], "article_id"=>877545, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Adriana Monserrath Orellana-Paucar", "Tatiana Afrikanova", "Joice Thomas", "Yelaman K. Aibuldinov", "Wim Dehaen", "Peter A. M. de Witte", "Camila V. Esguerra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081634.g006", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_the_effect_of_ar_turmerone_on_seizure_related_marker_expression_in_zebrafish_brains_/877545", "title"=>"Evaluation of the effect of ar-turmerone on seizure-related marker expression in zebrafish brains.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-13 03:11:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1314775"], "description"=>"<p>Chromatographic analysis of these samples showed evidence of the presence of ar-turmerone at 15 min and up to 24 hours after i.p administration of 50 mg/kg.</p>", "links"=>[], "tags"=>["ar-turmerone"], "article_id"=>877543, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Adriana Monserrath Orellana-Paucar", "Tatiana Afrikanova", "Joice Thomas", "Yelaman K. Aibuldinov", "Wim Dehaen", "Peter A. M. de Witte", "Camila V. Esguerra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081634.g005", "stats"=>{"downloads"=>4, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Concentration_8211_time_profile_of_ar_turmerone_in_mouse_brain_extracts_/877543", "title"=>"Concentration – time profile of ar-turmerone in mouse brain extracts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-13 03:11:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1314774"], "description"=>"<p>A) blank mouse brain extract, B) blank mouse brain extract spiked with ar-turmerone (AT) and internal standard (IS) and C) brain extract sample of a dosed mouse. </p>", "links"=>[], "tags"=>["hplc", "chromatograms", "homogenate", "ar-turmerone"], "article_id"=>877542, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Adriana Monserrath Orellana-Paucar", "Tatiana Afrikanova", "Joice Thomas", "Yelaman K. Aibuldinov", "Wim Dehaen", "Peter A. M. de Witte", "Camila V. Esguerra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081634.g004", "stats"=>{"downloads"=>11, "page_views"=>59, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_HPLC_chromatograms_of_mouse_brain_homogenate_analysis_for_ar_turmerone_determination_/877542", "title"=>"Representative HPLC chromatograms of mouse brain homogenate analysis for ar-turmerone determination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-13 03:11:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1314771"], "description"=>"<div><p><b>PTZ infusion model</b>. </p>\n\t\t\t\t\t\t<p>Radar graphic depicts the doses of PTZ required to trigger seven characteristic behavioral events (ET: ear twitch, MT: myoclonic twitch, TT: tail twitch, FC: forelimb clonus, F: falling, THE: tonic hindlimb extension, D: death) after i.v. administration of AT at 1 and 20 mg/kg compared to vehicle-treated mice (control). Levetiracetam (LEV) 50 mg/kg was included as a positive control. Results are expressed as relative values compared to control (set as 100%). For reasons of clarity, mean values (± SD) and statistically significant differences are not shown here (for details see Table 2).</p></div>", "links"=>[], "tags"=>["anticonvulsant", "ar-turmerone", "timed"], "article_id"=>877539, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Adriana Monserrath Orellana-Paucar", "Tatiana Afrikanova", "Joice Thomas", "Yelaman K. Aibuldinov", "Wim Dehaen", "Peter A. M. de Witte", "Camila V. Esguerra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081634.g002", "stats"=>{"downloads"=>4, "page_views"=>40, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_the_anticonvulsant_activity_of_ar_turmerone_AT_in_the_timed_i_v_/877539", "title"=>"Evaluation of the anticonvulsant activity of ar-turmerone (AT) in the timed i.v.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-13 03:11:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1314770"], "description"=>"<p>A) After 30 min of i.p. administration, complete protection was observed for ar-turmerone at a dose range of 0.1 - 50 mg/kg. A group of vehicle-treated mice (VHC) was included as a negative control. Sodium valproate at 300 mg/kg (VAL300) and levetiracetam at 50 mg/kg (LEV50) were used as positive controls. B) After 24 h i.p. administration (50 mg/kg), protection was observed after electrical induction. Statistically significant differences between control (VHC) and sample groups are labeled as * for p < 0.05 (Fisher’s exact test).</p>", "links"=>[], "tags"=>["anticonvulsant", "ar-turmerone", "6-hz"], "article_id"=>877538, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Adriana Monserrath Orellana-Paucar", "Tatiana Afrikanova", "Joice Thomas", "Yelaman K. Aibuldinov", "Wim Dehaen", "Peter A. M. de Witte", "Camila V. Esguerra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081634.g001", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_the_anticonvulsant_activity_of_ar_turmerone_AT_as_determined_by_the_6_Hz_model_/877538", "title"=>"Evaluation of the anticonvulsant activity of ar-turmerone (AT) as determined by the 6-Hz model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-13 03:11:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1314772"], "description"=>"<p>An intravenous dose of 50 mg/kg of ar-turmerone (AT) does not cause any alteration of motor skills in mice. Sensitivity of this model was confirmed by detection of motor and balance deficits induced by diazepam (DPZ) in mice at 1 mg/kg. Compared to control group (VHC), DZP-treated mice displayed a significant increase in number of footslips (A), falls (B) and time to reach goal box (C). Statistically significant differences between control and sample groups are labeled as ** for p < 0.001 (one-way ANOVA test).</p>", "links"=>[], "tags"=>["ar-turmerone"], "article_id"=>877540, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Adriana Monserrath Orellana-Paucar", "Tatiana Afrikanova", "Joice Thomas", "Yelaman K. Aibuldinov", "Wim Dehaen", "Peter A. M. de Witte", "Camila V. Esguerra"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081634.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_the_effect_of_ar_turmerone_on_mouse_motor_function_and_balance_/877540", "title"=>"Evaluation of the effect of ar-turmerone on mouse motor function and balance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-13 03:11:15"}

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  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"17", "full-text"=>"17", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"20", "full-text"=>"19", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"14", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"17", "full-text"=>"18", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"19", "full-text"=>"21", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"14", "full-text"=>"17", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Medicine and health sciences/Pharmaceutics", "average_usage"=>[254, 457, 591, 700, 808, 906, 1001, 1093, 1185, 1276, 1373, 1457, 1535]}, {"subject_area"=>"/Medicine and health sciences/Pharmacology", "average_usage"=>[265, 471, 604, 723, 827, 926, 1022, 1113, 1210, 1290, 1377, 1454, 1532]}]}
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