Bromoalkaloids Protect Primary Cortical Neurons from Induced Oxidative Stress
Bromoalkaloids are secondary metabolites with a demonstrated high activity in several therapeutic areas. In this research, we probe the neuroprotective and antioxidant activities of hymenialdisine and hymenin. Both structures were tested in an oxidative stress cellular model, consisting of cortical...
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| Veröffentlicht in: | ACS chemical neuroscience 2015-02, Vol.6 (2), p.331-338 |
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| creator | Leirós, M Alonso, E Rateb, M. E Houssen, W. E Ebel, R Jaspars, M Alfonso, A Botana, L. M |
| description | Bromoalkaloids are secondary metabolites with a demonstrated high activity in several therapeutic areas. In this research, we probe the neuroprotective and antioxidant activities of hymenialdisine and hymenin. Both structures were tested in an oxidative stress cellular model, consisting of cortical neurons that are incubated with the oxidative stress inducer hydrogen peroxide and the tested compound. Several oxidation biomarkers were analyzed, and the results of the oxidative stress induced neurons in the presence and absence of bromoalkaloids were compared. Both compounds demonstrated significant neuroprotective ability under stress conditions at low nanomolar concentrations, with hymenialdisine highlighted for demonstrating a more complete protection. Also, the activity of hymenialdisine and hymenin was studied in the nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathway, and, for the first time, these halogenated metabolites are described as Nrf2 inducers, reinforcing the antioxidant capacity observed and therefore opening a new path of investigation. These results, added to the previously described effect of this compound family in negatively modulating several kinases and proinflammatory cytokines, position hymenialdisine and hymenin as good candidates for the development of new drugs for neurodegenerative diseases. |
| doi_str_mv | 10.1021/cn500258c |
| format | Article |
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E ; Houssen, W. E ; Ebel, R ; Jaspars, M ; Alfonso, A ; Botana, L. M</creator><creatorcontrib>Leirós, M ; Alonso, E ; Rateb, M. E ; Houssen, W. E ; Ebel, R ; Jaspars, M ; Alfonso, A ; Botana, L. M</creatorcontrib><description>Bromoalkaloids are secondary metabolites with a demonstrated high activity in several therapeutic areas. In this research, we probe the neuroprotective and antioxidant activities of hymenialdisine and hymenin. Both structures were tested in an oxidative stress cellular model, consisting of cortical neurons that are incubated with the oxidative stress inducer hydrogen peroxide and the tested compound. Several oxidation biomarkers were analyzed, and the results of the oxidative stress induced neurons in the presence and absence of bromoalkaloids were compared. Both compounds demonstrated significant neuroprotective ability under stress conditions at low nanomolar concentrations, with hymenialdisine highlighted for demonstrating a more complete protection. Also, the activity of hymenialdisine and hymenin was studied in the nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathway, and, for the first time, these halogenated metabolites are described as Nrf2 inducers, reinforcing the antioxidant capacity observed and therefore opening a new path of investigation. These results, added to the previously described effect of this compound family in negatively modulating several kinases and proinflammatory cytokines, position hymenialdisine and hymenin as good candidates for the development of new drugs for neurodegenerative diseases.</description><identifier>ISSN: 1948-7193</identifier><identifier>EISSN: 1948-7193</identifier><identifier>DOI: 10.1021/cn500258c</identifier><identifier>PMID: 25387680</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Alkaloids - chemistry ; Alkaloids - pharmacology ; Animals ; Antioxidant Response Elements - physiology ; Azepines - chemistry ; Azepines - pharmacology ; Blotting, Western ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Cell Survival - drug effects ; Cell Survival - physiology ; Cells, Cultured ; Cerebral Cortex - drug effects ; Cerebral Cortex - pathology ; Cerebral Cortex - physiology ; Lipid Peroxidation - drug effects ; Lipid Peroxidation - physiology ; Mice ; Microscopy, Confocal ; Mitochondria - drug effects ; Mitochondria - metabolism ; Neurons - drug effects ; Neurons - pathology ; Neurons - physiology ; Neuroprotective Agents - pharmacology ; NF-E2-Related Factor 2 - metabolism ; Oxidative Stress - drug effects ; Oxidative Stress - physiology ; Pyrroles - chemistry ; Pyrroles - pharmacology ; Sesquiterpenes - chemistry ; Sesquiterpenes - pharmacology ; Signal Transduction - drug effects</subject><ispartof>ACS chemical neuroscience, 2015-02, Vol.6 (2), p.331-338</ispartof><rights>Copyright © 2014 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a315t-74161813075cd848660c29a25ed1451690db8978235248b7d3fd63cb42156ea93</citedby><cites>FETCH-LOGICAL-a315t-74161813075cd848660c29a25ed1451690db8978235248b7d3fd63cb42156ea93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/cn500258c$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/cn500258c$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25387680$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leirós, M</creatorcontrib><creatorcontrib>Alonso, E</creatorcontrib><creatorcontrib>Rateb, M. E</creatorcontrib><creatorcontrib>Houssen, W. E</creatorcontrib><creatorcontrib>Ebel, R</creatorcontrib><creatorcontrib>Jaspars, M</creatorcontrib><creatorcontrib>Alfonso, A</creatorcontrib><creatorcontrib>Botana, L. M</creatorcontrib><title>Bromoalkaloids Protect Primary Cortical Neurons from Induced Oxidative Stress</title><title>ACS chemical neuroscience</title><addtitle>ACS Chem. Neurosci</addtitle><description>Bromoalkaloids are secondary metabolites with a demonstrated high activity in several therapeutic areas. In this research, we probe the neuroprotective and antioxidant activities of hymenialdisine and hymenin. Both structures were tested in an oxidative stress cellular model, consisting of cortical neurons that are incubated with the oxidative stress inducer hydrogen peroxide and the tested compound. Several oxidation biomarkers were analyzed, and the results of the oxidative stress induced neurons in the presence and absence of bromoalkaloids were compared. Both compounds demonstrated significant neuroprotective ability under stress conditions at low nanomolar concentrations, with hymenialdisine highlighted for demonstrating a more complete protection. Also, the activity of hymenialdisine and hymenin was studied in the nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathway, and, for the first time, these halogenated metabolites are described as Nrf2 inducers, reinforcing the antioxidant capacity observed and therefore opening a new path of investigation. These results, added to the previously described effect of this compound family in negatively modulating several kinases and proinflammatory cytokines, position hymenialdisine and hymenin as good candidates for the development of new drugs for neurodegenerative diseases.</description><subject>Alkaloids - chemistry</subject><subject>Alkaloids - pharmacology</subject><subject>Animals</subject><subject>Antioxidant Response Elements - physiology</subject><subject>Azepines - chemistry</subject><subject>Azepines - pharmacology</subject><subject>Blotting, Western</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - physiology</subject><subject>Cells, Cultured</subject><subject>Cerebral Cortex - drug effects</subject><subject>Cerebral Cortex - pathology</subject><subject>Cerebral Cortex - physiology</subject><subject>Lipid Peroxidation - drug effects</subject><subject>Lipid Peroxidation - physiology</subject><subject>Mice</subject><subject>Microscopy, Confocal</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Neurons - drug effects</subject><subject>Neurons - pathology</subject><subject>Neurons - physiology</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - physiology</subject><subject>Pyrroles - chemistry</subject><subject>Pyrroles - pharmacology</subject><subject>Sesquiterpenes - chemistry</subject><subject>Sesquiterpenes - pharmacology</subject><subject>Signal Transduction - drug effects</subject><issn>1948-7193</issn><issn>1948-7193</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1LxDAURYMozji68A9IN4IuqnlJk6ZLLX4MjI6grkuapNCxbcYkFf33VjoOLlzdtzgc3r0IHQO-AEzgUnUMY8KE2kFTyBIRp5DR3T_3BB14v8KYZ1jwfTQhjIqUCzxFD9fOtlY2b7KxtfbRk7PBqDBk3Ur3FeXWhVrJJno0vbOdj6qBj-ad7pXR0fKz1jLUHyZ6Ds54f4j2Ktl4c7TJGXq9vXnJ7-PF8m6eXy1iSYGFOE2AgwCKU6a0SATnWJFMEmY0JAyGL3UpslQQykgiylTTSnOqyoQA40ZmdIbORu_a2ffe-FC0tVemaWRnbO8L4CylkAmKB_R8RJWz3jtTFeuxWgG4-Fmv2K43sCcbbV-2Rm_J37kG4HQEpPLFyvauG1r-I_oGech0uQ</recordid><startdate>20150218</startdate><enddate>20150218</enddate><creator>Leirós, M</creator><creator>Alonso, E</creator><creator>Rateb, M. 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M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a315t-74161813075cd848660c29a25ed1451690db8978235248b7d3fd63cb42156ea93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Alkaloids - chemistry</topic><topic>Alkaloids - pharmacology</topic><topic>Animals</topic><topic>Antioxidant Response Elements - physiology</topic><topic>Azepines - chemistry</topic><topic>Azepines - pharmacology</topic><topic>Blotting, Western</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - physiology</topic><topic>Cells, Cultured</topic><topic>Cerebral Cortex - drug effects</topic><topic>Cerebral Cortex - pathology</topic><topic>Cerebral Cortex - physiology</topic><topic>Lipid Peroxidation - drug effects</topic><topic>Lipid Peroxidation - physiology</topic><topic>Mice</topic><topic>Microscopy, Confocal</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Neurons - drug effects</topic><topic>Neurons - pathology</topic><topic>Neurons - physiology</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxidative Stress - physiology</topic><topic>Pyrroles - chemistry</topic><topic>Pyrroles - pharmacology</topic><topic>Sesquiterpenes - chemistry</topic><topic>Sesquiterpenes - pharmacology</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leirós, M</creatorcontrib><creatorcontrib>Alonso, E</creatorcontrib><creatorcontrib>Rateb, M. E</creatorcontrib><creatorcontrib>Houssen, W. E</creatorcontrib><creatorcontrib>Ebel, R</creatorcontrib><creatorcontrib>Jaspars, M</creatorcontrib><creatorcontrib>Alfonso, A</creatorcontrib><creatorcontrib>Botana, L. M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>ACS chemical neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leirós, M</au><au>Alonso, E</au><au>Rateb, M. E</au><au>Houssen, W. E</au><au>Ebel, R</au><au>Jaspars, M</au><au>Alfonso, A</au><au>Botana, L. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bromoalkaloids Protect Primary Cortical Neurons from Induced Oxidative Stress</atitle><jtitle>ACS chemical neuroscience</jtitle><addtitle>ACS Chem. Neurosci</addtitle><date>2015-02-18</date><risdate>2015</risdate><volume>6</volume><issue>2</issue><spage>331</spage><epage>338</epage><pages>331-338</pages><issn>1948-7193</issn><eissn>1948-7193</eissn><abstract>Bromoalkaloids are secondary metabolites with a demonstrated high activity in several therapeutic areas. In this research, we probe the neuroprotective and antioxidant activities of hymenialdisine and hymenin. Both structures were tested in an oxidative stress cellular model, consisting of cortical neurons that are incubated with the oxidative stress inducer hydrogen peroxide and the tested compound. Several oxidation biomarkers were analyzed, and the results of the oxidative stress induced neurons in the presence and absence of bromoalkaloids were compared. Both compounds demonstrated significant neuroprotective ability under stress conditions at low nanomolar concentrations, with hymenialdisine highlighted for demonstrating a more complete protection. Also, the activity of hymenialdisine and hymenin was studied in the nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathway, and, for the first time, these halogenated metabolites are described as Nrf2 inducers, reinforcing the antioxidant capacity observed and therefore opening a new path of investigation. These results, added to the previously described effect of this compound family in negatively modulating several kinases and proinflammatory cytokines, position hymenialdisine and hymenin as good candidates for the development of new drugs for neurodegenerative diseases.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>25387680</pmid><doi>10.1021/cn500258c</doi><tpages>8</tpages></addata></record> |
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| subjects | Alkaloids - chemistry Alkaloids - pharmacology Animals Antioxidant Response Elements - physiology Azepines - chemistry Azepines - pharmacology Blotting, Western Cell Membrane - drug effects Cell Membrane - metabolism Cell Survival - drug effects Cell Survival - physiology Cells, Cultured Cerebral Cortex - drug effects Cerebral Cortex - pathology Cerebral Cortex - physiology Lipid Peroxidation - drug effects Lipid Peroxidation - physiology Mice Microscopy, Confocal Mitochondria - drug effects Mitochondria - metabolism Neurons - drug effects Neurons - pathology Neurons - physiology Neuroprotective Agents - pharmacology NF-E2-Related Factor 2 - metabolism Oxidative Stress - drug effects Oxidative Stress - physiology Pyrroles - chemistry Pyrroles - pharmacology Sesquiterpenes - chemistry Sesquiterpenes - pharmacology Signal Transduction - drug effects |
| title | Bromoalkaloids Protect Primary Cortical Neurons from Induced Oxidative Stress |
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