Withanolide A prevents neurodegeneration by modulating hippocampal glutathione biosynthesis during hypoxia
Withania somnifera root extract has been used traditionally in ayurvedic system of medicine as a memory enhancer. Present study explores the ameliorative effect of withanolide A, a major component of withania root extract and its molecular mechanism against hypoxia induced memory impairment. Withano...
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| description | Withania somnifera root extract has been used traditionally in ayurvedic system of medicine as a memory enhancer. Present study explores the ameliorative effect of withanolide A, a major component of withania root extract and its molecular mechanism against hypoxia induced memory impairment. Withanolide A was administered to male Sprague Dawley rats before a period of 21 days pre-exposure and during 07 days of exposure to a simulated altitude of 25,000 ft. Glutathione level and glutathione dependent free radicals scavenging enzyme system, ATP, NADPH level, γ-glutamylcysteinyl ligase (GCLC) activity and oxidative stress markers were assessed in the hippocampus. Expression of apoptotic marker caspase 3 in hippocampus was investigated by immunohistochemistry. Transcriptional alteration and expression of GCLC and Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) were investigated by real time PCR and immunoblotting respectively. Exposure to hypobaric hypoxia decreased reduced glutathione (GSH) level and impaired reduced gluatathione dependent free radical scavenging system in hippocampus resulting in elevated oxidative stress. Supplementation of withanolide A during hypoxic exposure increased GSH level, augmented GSH dependent free radicals scavenging system and decreased the number of caspase and hoescht positive cells in hippocampus. While withanolide A reversed hypoxia mediated neurodegeneration, administration of buthionine sulfoximine along with withanolide A blunted its neuroprotective effects. Exogenous administration of corticosterone suppressed Nrf2 and GCLC expression whereas inhibition of corticosterone synthesis upregulated Nrf2 as well as GCLC. Thus present study infers that withanolide A reduces neurodegeneration by restoring hypoxia induced glutathione depletion in hippocampus. Further, Withanolide A increases glutathione biosynthesis in neuronal cells by upregulating GCLC level through Nrf2 pathway in a corticosterone dependenet manner. |
| doi_str_mv | 10.1371/journal.pone.0105311 |
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Present study explores the ameliorative effect of withanolide A, a major component of withania root extract and its molecular mechanism against hypoxia induced memory impairment. Withanolide A was administered to male Sprague Dawley rats before a period of 21 days pre-exposure and during 07 days of exposure to a simulated altitude of 25,000 ft. Glutathione level and glutathione dependent free radicals scavenging enzyme system, ATP, NADPH level, γ-glutamylcysteinyl ligase (GCLC) activity and oxidative stress markers were assessed in the hippocampus. Expression of apoptotic marker caspase 3 in hippocampus was investigated by immunohistochemistry. Transcriptional alteration and expression of GCLC and Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) were investigated by real time PCR and immunoblotting respectively. Exposure to hypobaric hypoxia decreased reduced glutathione (GSH) level and impaired reduced gluatathione dependent free radical scavenging system in hippocampus resulting in elevated oxidative stress. Supplementation of withanolide A during hypoxic exposure increased GSH level, augmented GSH dependent free radicals scavenging system and decreased the number of caspase and hoescht positive cells in hippocampus. While withanolide A reversed hypoxia mediated neurodegeneration, administration of buthionine sulfoximine along with withanolide A blunted its neuroprotective effects. Exogenous administration of corticosterone suppressed Nrf2 and GCLC expression whereas inhibition of corticosterone synthesis upregulated Nrf2 as well as GCLC. Thus present study infers that withanolide A reduces neurodegeneration by restoring hypoxia induced glutathione depletion in hippocampus. Further, Withanolide A increases glutathione biosynthesis in neuronal cells by upregulating GCLC level through Nrf2 pathway in a corticosterone dependenet manner.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0105311</identifier><identifier>PMID: 25310001</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antioxidants ; Apoptosis ; Apoptosis - drug effects ; Biology and Life Sciences ; Biosynthesis ; Brain research ; Buthionine sulfoximine ; Caspase ; Caspase 3 - metabolism ; Caspase-3 ; Corticosterone ; Corticosterone - pharmacology ; Dopamine ; Enzymes ; Exposure ; Free radicals ; Free Radicals - metabolism ; Gene expression ; Glutamate-Cysteine Ligase - genetics ; Glutamate-Cysteine Ligase - metabolism ; Glutathione ; Glutathione - biosynthesis ; Hippocampus ; Hippocampus - drug effects ; Hippocampus - metabolism ; Hypoxia ; Hypoxia - metabolism ; Immunoblotting ; Immunohistochemistry ; Ligases ; Lipid peroxidation ; Male ; Maze Learning - drug effects ; Memory ; Memory - drug effects ; NADP ; Nerve Degeneration - drug therapy ; Nerve Degeneration - etiology ; Nerve Degeneration - metabolism ; Neurobiology ; Neurodegeneration ; Neuroprotection ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; Neurosciences ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; Nitric oxide ; Oxidative stress ; Oxidative Stress - drug effects ; Physiological aspects ; Physiology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species - metabolism ; Receptors, Glucocorticoid - genetics ; Receptors, Glucocorticoid - metabolism ; Receptors, Mineralocorticoid - genetics ; Receptors, Mineralocorticoid - metabolism ; Rodents ; Scavenging ; Superoxide Dismutase - metabolism ; Supplements ; Thiols ; Transcription ; Transcription, Genetic - drug effects ; Withania somnifera ; Withanolides - pharmacology ; Withanolides - therapeutic use ; Zoology</subject><ispartof>PloS one, 2014-10, Vol.9 (10), p.e105311</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Baitharu 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 Baitharu et al 2014 Baitharu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-ff8852bbda1e73cb9b8b25843b0ddf8645d208110b39829bb866e2059cf918c13</citedby><cites>FETCH-LOGICAL-c692t-ff8852bbda1e73cb9b8b25843b0ddf8645d208110b39829bb866e2059cf918c13</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/PMC4195593/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195593/$$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/25310001$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baitharu, Iswar</creatorcontrib><creatorcontrib>Jain, Vishal</creatorcontrib><creatorcontrib>Deep, Satya Narayan</creatorcontrib><creatorcontrib>Shroff, Sabita</creatorcontrib><creatorcontrib>Sahu, Jayanta Kumar</creatorcontrib><creatorcontrib>Naik, Pradeep Kumar</creatorcontrib><creatorcontrib>Ilavazhagan, Govindasamy</creatorcontrib><title>Withanolide A prevents neurodegeneration by modulating hippocampal glutathione biosynthesis during hypoxia</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Withania somnifera root extract has been used traditionally in ayurvedic system of medicine as a memory enhancer. Present study explores the ameliorative effect of withanolide A, a major component of withania root extract and its molecular mechanism against hypoxia induced memory impairment. Withanolide A was administered to male Sprague Dawley rats before a period of 21 days pre-exposure and during 07 days of exposure to a simulated altitude of 25,000 ft. Glutathione level and glutathione dependent free radicals scavenging enzyme system, ATP, NADPH level, γ-glutamylcysteinyl ligase (GCLC) activity and oxidative stress markers were assessed in the hippocampus. Expression of apoptotic marker caspase 3 in hippocampus was investigated by immunohistochemistry. Transcriptional alteration and expression of GCLC and Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) were investigated by real time PCR and immunoblotting respectively. Exposure to hypobaric hypoxia decreased reduced glutathione (GSH) level and impaired reduced gluatathione dependent free radical scavenging system in hippocampus resulting in elevated oxidative stress. Supplementation of withanolide A during hypoxic exposure increased GSH level, augmented GSH dependent free radicals scavenging system and decreased the number of caspase and hoescht positive cells in hippocampus. While withanolide A reversed hypoxia mediated neurodegeneration, administration of buthionine sulfoximine along with withanolide A blunted its neuroprotective effects. Exogenous administration of corticosterone suppressed Nrf2 and GCLC expression whereas inhibition of corticosterone synthesis upregulated Nrf2 as well as GCLC. Thus present study infers that withanolide A reduces neurodegeneration by restoring hypoxia induced glutathione depletion in hippocampus. Further, Withanolide A increases glutathione biosynthesis in neuronal cells by upregulating GCLC level through Nrf2 pathway in a corticosterone dependenet manner.</description><subject>Animals</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biology and Life Sciences</subject><subject>Biosynthesis</subject><subject>Brain research</subject><subject>Buthionine sulfoximine</subject><subject>Caspase</subject><subject>Caspase 3 - metabolism</subject><subject>Caspase-3</subject><subject>Corticosterone</subject><subject>Corticosterone - pharmacology</subject><subject>Dopamine</subject><subject>Enzymes</subject><subject>Exposure</subject><subject>Free radicals</subject><subject>Free Radicals - metabolism</subject><subject>Gene expression</subject><subject>Glutamate-Cysteine Ligase - genetics</subject><subject>Glutamate-Cysteine Ligase - metabolism</subject><subject>Glutathione</subject><subject>Glutathione - biosynthesis</subject><subject>Hippocampus</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Hypoxia</subject><subject>Hypoxia - metabolism</subject><subject>Immunoblotting</subject><subject>Immunohistochemistry</subject><subject>Ligases</subject><subject>Lipid peroxidation</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>Memory</subject><subject>Memory - drug effects</subject><subject>NADP</subject><subject>Nerve Degeneration - drug therapy</subject><subject>Nerve Degeneration - etiology</subject><subject>Nerve Degeneration - metabolism</subject><subject>Neurobiology</subject><subject>Neurodegeneration</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Neurosciences</subject><subject>NF-E2-Related Factor 2 - genetics</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Nitric oxide</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Receptors, Glucocorticoid - genetics</subject><subject>Receptors, Glucocorticoid - metabolism</subject><subject>Receptors, Mineralocorticoid - genetics</subject><subject>Receptors, Mineralocorticoid - metabolism</subject><subject>Rodents</subject><subject>Scavenging</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Supplements</subject><subject>Thiols</subject><subject>Transcription</subject><subject>Transcription, Genetic - drug effects</subject><subject>Withania somnifera</subject><subject>Withanolides - pharmacology</subject><subject>Withanolides - therapeutic use</subject><subject>Zoology</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>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkllr3DAUhU1padK0_6C0hkKhDzOV5GWkl8IQugwEAl0fhZZrW4MtuZIcMv--SsYJMbRQ9KDtu0fS0cmylxitcbHB7_du8lb069FZWCOMqgLjR9kpZgVZ1QQVjx-MT7JnIexRYmhdP81OSIIRQvg02_8ysRPW9UZDvs1HD1dgY8gtTN5paMGCF9E4m8tDPjg99Wlm27wz4-iUGEbR520_RRG7BEEujQsHGzsIJuR68rfsYXTXRjzPnjSiD_Bi7s-yH58-fj__srq4_Lw7316sVM1IXDUNpRWRUgsMm0JJJqkkFS0LibRuaF1WmiCKMZIFo4RJmZ4EBFVMNQxThYuz7PVRd-xd4LNNgeMaI8bIpqoSsTsS2ok9H70ZhD9wJwy_XXC-5cJHo3rgVDJUEyElUVBKJhjesAIppWmtQWORtD7Mp01yAK2Se170C9HljjUdb90VLzGrKlYkgTezgHe_JwjxH1eeqVakWxnbuCSmBhMU35aYJoJs6kSt_0KlpmEwKv1PY9L6ouDdoiAxEa5jK6YQ-O7b1_9nL38u2bcP2A5EH7vgUk5SSMISLI-g8i4ED829cxjxm5zfucFvcs7nnKeyVw9dvy-6C3bxB7Fo-wE</recordid><startdate>20141013</startdate><enddate>20141013</enddate><creator>Baitharu, Iswar</creator><creator>Jain, Vishal</creator><creator>Deep, Satya Narayan</creator><creator>Shroff, Sabita</creator><creator>Sahu, Jayanta Kumar</creator><creator>Naik, Pradeep Kumar</creator><creator>Ilavazhagan, Govindasamy</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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141013</creationdate><title>Withanolide A prevents neurodegeneration by modulating hippocampal glutathione biosynthesis during hypoxia</title><author>Baitharu, Iswar ; Jain, Vishal ; Deep, Satya Narayan ; Shroff, Sabita ; Sahu, Jayanta Kumar ; Naik, Pradeep Kumar ; Ilavazhagan, Govindasamy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-ff8852bbda1e73cb9b8b25843b0ddf8645d208110b39829bb866e2059cf918c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Biology and Life Sciences</topic><topic>Biosynthesis</topic><topic>Brain research</topic><topic>Buthionine sulfoximine</topic><topic>Caspase</topic><topic>Caspase 3 - metabolism</topic><topic>Caspase-3</topic><topic>Corticosterone</topic><topic>Corticosterone - pharmacology</topic><topic>Dopamine</topic><topic>Enzymes</topic><topic>Exposure</topic><topic>Free radicals</topic><topic>Free Radicals - metabolism</topic><topic>Gene expression</topic><topic>Glutamate-Cysteine Ligase - genetics</topic><topic>Glutamate-Cysteine Ligase - metabolism</topic><topic>Glutathione</topic><topic>Glutathione - biosynthesis</topic><topic>Hippocampus</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Hypoxia</topic><topic>Hypoxia - metabolism</topic><topic>Immunoblotting</topic><topic>Immunohistochemistry</topic><topic>Ligases</topic><topic>Lipid peroxidation</topic><topic>Male</topic><topic>Maze Learning - drug effects</topic><topic>Memory</topic><topic>Memory - 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metabolism</topic><topic>Supplements</topic><topic>Thiols</topic><topic>Transcription</topic><topic>Transcription, Genetic - drug effects</topic><topic>Withania somnifera</topic><topic>Withanolides - pharmacology</topic><topic>Withanolides - therapeutic use</topic><topic>Zoology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baitharu, Iswar</creatorcontrib><creatorcontrib>Jain, Vishal</creatorcontrib><creatorcontrib>Deep, Satya Narayan</creatorcontrib><creatorcontrib>Shroff, Sabita</creatorcontrib><creatorcontrib>Sahu, Jayanta Kumar</creatorcontrib><creatorcontrib>Naik, Pradeep Kumar</creatorcontrib><creatorcontrib>Ilavazhagan, Govindasamy</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 - 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Present study explores the ameliorative effect of withanolide A, a major component of withania root extract and its molecular mechanism against hypoxia induced memory impairment. Withanolide A was administered to male Sprague Dawley rats before a period of 21 days pre-exposure and during 07 days of exposure to a simulated altitude of 25,000 ft. Glutathione level and glutathione dependent free radicals scavenging enzyme system, ATP, NADPH level, γ-glutamylcysteinyl ligase (GCLC) activity and oxidative stress markers were assessed in the hippocampus. Expression of apoptotic marker caspase 3 in hippocampus was investigated by immunohistochemistry. Transcriptional alteration and expression of GCLC and Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) were investigated by real time PCR and immunoblotting respectively. Exposure to hypobaric hypoxia decreased reduced glutathione (GSH) level and impaired reduced gluatathione dependent free radical scavenging system in hippocampus resulting in elevated oxidative stress. Supplementation of withanolide A during hypoxic exposure increased GSH level, augmented GSH dependent free radicals scavenging system and decreased the number of caspase and hoescht positive cells in hippocampus. While withanolide A reversed hypoxia mediated neurodegeneration, administration of buthionine sulfoximine along with withanolide A blunted its neuroprotective effects. Exogenous administration of corticosterone suppressed Nrf2 and GCLC expression whereas inhibition of corticosterone synthesis upregulated Nrf2 as well as GCLC. Thus present study infers that withanolide A reduces neurodegeneration by restoring hypoxia induced glutathione depletion in hippocampus. Further, Withanolide A increases glutathione biosynthesis in neuronal cells by upregulating GCLC level through Nrf2 pathway in a corticosterone dependenet manner.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25310001</pmid><doi>10.1371/journal.pone.0105311</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-10, Vol.9 (10), p.e105311 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1610992755 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Animals Antioxidants Apoptosis Apoptosis - drug effects Biology and Life Sciences Biosynthesis Brain research Buthionine sulfoximine Caspase Caspase 3 - metabolism Caspase-3 Corticosterone Corticosterone - pharmacology Dopamine Enzymes Exposure Free radicals Free Radicals - metabolism Gene expression Glutamate-Cysteine Ligase - genetics Glutamate-Cysteine Ligase - metabolism Glutathione Glutathione - biosynthesis Hippocampus Hippocampus - drug effects Hippocampus - metabolism Hypoxia Hypoxia - metabolism Immunoblotting Immunohistochemistry Ligases Lipid peroxidation Male Maze Learning - drug effects Memory Memory - drug effects NADP Nerve Degeneration - drug therapy Nerve Degeneration - etiology Nerve Degeneration - metabolism Neurobiology Neurodegeneration Neuroprotection Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Neurosciences NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism Nitric oxide Oxidative stress Oxidative Stress - drug effects Physiological aspects Physiology Rats Rats, Sprague-Dawley Reactive Oxygen Species - metabolism Receptors, Glucocorticoid - genetics Receptors, Glucocorticoid - metabolism Receptors, Mineralocorticoid - genetics Receptors, Mineralocorticoid - metabolism Rodents Scavenging Superoxide Dismutase - metabolism Supplements Thiols Transcription Transcription, Genetic - drug effects Withania somnifera Withanolides - pharmacology Withanolides - therapeutic use Zoology |
| title | Withanolide A prevents neurodegeneration by modulating hippocampal glutathione biosynthesis during hypoxia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T22%3A23%3A39IST&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=Withanolide%20A%20prevents%20neurodegeneration%20by%20modulating%20hippocampal%20glutathione%20biosynthesis%20during%20hypoxia&rft.jtitle=PloS%20one&rft.au=Baitharu,%20Iswar&rft.date=2014-10-13&rft.volume=9&rft.issue=10&rft.spage=e105311&rft.pages=e105311-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0105311&rft_dat=%3Cgale_plos_%3EA418553276%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=1610992755&rft_id=info:pmid/25310001&rft_galeid=A418553276&rft_doaj_id=oai_doaj_org_article_8b9062abb2ce4b9a917930ccd86ded1a&rfr_iscdi=true |