Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease
1. In the brains of patients with Alzheimer's disease (AD) signs of neuronal degeneration are accompanied by markers of microglial activation, inflammation, and oxidant damage. The presence of nitrotyrosine in the cell bodies of neurons in AD suggests that peroxynitrite contributes to the patho...
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| Veröffentlicht in: | Progress in neuro-psychopharmacology & biological psychiatry 2001-10, Vol.25 (7), p.1341-1357 |
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| container_title | Progress in neuro-psychopharmacology & biological psychiatry |
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| creator | Allison, Anthony C. Cacabelos, Ramon Lombardi, Valter R.M. Álvarez, Xoan A. Vigo, Carmen |
| description | 1.
In the brains of patients with Alzheimer's disease (AD) signs of neuronal degeneration are accompanied by markers of microglial activation, inflammation, and oxidant damage. The presence of nitrotyrosine in the cell bodies of neurons in AD suggests that peroxynitrite contributes to the pathogenesis of the disease.
2.
A drug with antioxidant and anti-inflammatory activity may prevent neuronal degeneration in AD. Celastrol, a plant-derived triterpene, has these effects.
3.
In low nanomolar concentrations celastrol was found to suppress the production by human monocytes and macrophages of the pro-inflammatory cytokines TNF-α and IL-1β.
4.
Celastrol also decreased the induced expression of class II MHC molecules by microglia. In macrophage lineage cells and endothelial cells celastrol decreased induced but not constitutive NO production.
5.
Celastrol suppressed adjuvant arthritis in the rat, demonstrating
in vivo anti-inflammatory activity. Low doses of celastrol administered to rats significantly improved their performance in memory, learning and psychomotor activity tests.
6.
The potent antioxidant and anti-inflammatory activities of celastrol, and its effects on cognitive functions, suggest that the drug may be useful to treat neurodegenerative diseases accompanied by inflammation, such as AD. |
| doi_str_mv | 10.1016/S0278-5846(01)00192-0 |
| format | Article |
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In the brains of patients with Alzheimer's disease (AD) signs of neuronal degeneration are accompanied by markers of microglial activation, inflammation, and oxidant damage. The presence of nitrotyrosine in the cell bodies of neurons in AD suggests that peroxynitrite contributes to the pathogenesis of the disease.
2.
A drug with antioxidant and anti-inflammatory activity may prevent neuronal degeneration in AD. Celastrol, a plant-derived triterpene, has these effects.
3.
In low nanomolar concentrations celastrol was found to suppress the production by human monocytes and macrophages of the pro-inflammatory cytokines TNF-α and IL-1β.
4.
Celastrol also decreased the induced expression of class II MHC molecules by microglia. In macrophage lineage cells and endothelial cells celastrol decreased induced but not constitutive NO production.
5.
Celastrol suppressed adjuvant arthritis in the rat, demonstrating
in vivo anti-inflammatory activity. Low doses of celastrol administered to rats significantly improved their performance in memory, learning and psychomotor activity tests.
6.
The potent antioxidant and anti-inflammatory activities of celastrol, and its effects on cognitive functions, suggest that the drug may be useful to treat neurodegenerative diseases accompanied by inflammation, such as AD.</description><identifier>ISSN: 0278-5846</identifier><identifier>EISSN: 1878-4216</identifier><identifier>DOI: 10.1016/S0278-5846(01)00192-0</identifier><identifier>PMID: 11513350</identifier><identifier>CODEN: PNPPD7</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Alzheimer Disease - drug therapy ; Alzheimer Disease - metabolism ; Alzheimer's disease ; Animals ; anti-inflammatory ; Anti-Inflammatory Agents, Non-Steroidal - chemistry ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use ; antioxidant ; Antioxidants - chemistry ; Antioxidants - pharmacology ; Antioxidants - therapeutic use ; Biological and medical sciences ; celastrol ; General pharmacology ; Humans ; Medical sciences ; Pharmacognosy. Homeopathy. Health food ; Pharmacology. Drug treatments ; Triterpenes - chemistry ; Triterpenes - pharmacology ; Triterpenes - therapeutic use</subject><ispartof>Progress in neuro-psychopharmacology & biological psychiatry, 2001-10, Vol.25 (7), p.1341-1357</ispartof><rights>2001</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-89a32d72dba68237a00be638cd4f44dad686606c85d62fb88c840621edb0d5b3</citedby><cites>FETCH-LOGICAL-c539t-89a32d72dba68237a00be638cd4f44dad686606c85d62fb88c840621edb0d5b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0278-5846(01)00192-0$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27928,27929,45999</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1075631$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11513350$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Allison, Anthony C.</creatorcontrib><creatorcontrib>Cacabelos, Ramon</creatorcontrib><creatorcontrib>Lombardi, Valter R.M.</creatorcontrib><creatorcontrib>Álvarez, Xoan A.</creatorcontrib><creatorcontrib>Vigo, Carmen</creatorcontrib><title>Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease</title><title>Progress in neuro-psychopharmacology & biological psychiatry</title><addtitle>Prog Neuropsychopharmacol Biol Psychiatry</addtitle><description>1.
In the brains of patients with Alzheimer's disease (AD) signs of neuronal degeneration are accompanied by markers of microglial activation, inflammation, and oxidant damage. The presence of nitrotyrosine in the cell bodies of neurons in AD suggests that peroxynitrite contributes to the pathogenesis of the disease.
2.
A drug with antioxidant and anti-inflammatory activity may prevent neuronal degeneration in AD. Celastrol, a plant-derived triterpene, has these effects.
3.
In low nanomolar concentrations celastrol was found to suppress the production by human monocytes and macrophages of the pro-inflammatory cytokines TNF-α and IL-1β.
4.
Celastrol also decreased the induced expression of class II MHC molecules by microglia. In macrophage lineage cells and endothelial cells celastrol decreased induced but not constitutive NO production.
5.
Celastrol suppressed adjuvant arthritis in the rat, demonstrating
in vivo anti-inflammatory activity. Low doses of celastrol administered to rats significantly improved their performance in memory, learning and psychomotor activity tests.
6.
The potent antioxidant and anti-inflammatory activities of celastrol, and its effects on cognitive functions, suggest that the drug may be useful to treat neurodegenerative diseases accompanied by inflammation, such as AD.</description><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>anti-inflammatory</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - chemistry</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</subject><subject>antioxidant</subject><subject>Antioxidants - chemistry</subject><subject>Antioxidants - pharmacology</subject><subject>Antioxidants - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>celastrol</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Pharmacognosy. Homeopathy. Health food</subject><subject>Pharmacology. Drug treatments</subject><subject>Triterpenes - chemistry</subject><subject>Triterpenes - pharmacology</subject><subject>Triterpenes - therapeutic use</subject><issn>0278-5846</issn><issn>1878-4216</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxS0EokvhI4ByQAUkAjNx4jgnVK34J1XiQO_WxJ6AwUkW24son55sdgXcevLY-r0Zz3tCPEZ4hYDq9WeoWl02ulbPAV8AYFeVcEdsUC_PdYXqrtj8Rc7Eg5S-wUJJkPfFGWKDUjawEd-3HCjlOIeXBRW7OfOUC5qyn395R2vt1nvppyHQOFKe403h4v7LIkirJiXfBy5yZMrjQT_MsbgMv7-yHzk-S4XziSnxQ3FvoJD40ek8F9fv3l5vP5RXn95_3F5elbaRXS51R7JybeV6UrqSLQH0rKS2rh7q2pFTWilQVjdOVUOvtdU1qArZ9eCaXp6Li2PbXZx_7DllM_pkOQSaeN4n0yKC1p26FUSNGjp1AJsjaOOybOTB7KIfKd4YBHNIw6xpmIPVBtCsaRhYdE9OA_b9yO6f6mT_Ajw9AZQshSHSZH36r3vbKIkL9uaI8eLaT8_RJOt5sux8ZJuNm_0tP_kD8fOm2g</recordid><startdate>20011001</startdate><enddate>20011001</enddate><creator>Allison, Anthony C.</creator><creator>Cacabelos, Ramon</creator><creator>Lombardi, Valter R.M.</creator><creator>Álvarez, Xoan A.</creator><creator>Vigo, Carmen</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20011001</creationdate><title>Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease</title><author>Allison, Anthony C. ; Cacabelos, Ramon ; Lombardi, Valter R.M. ; Álvarez, Xoan A. ; Vigo, Carmen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-89a32d72dba68237a00be638cd4f44dad686606c85d62fb88c840621edb0d5b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer's disease</topic><topic>Animals</topic><topic>anti-inflammatory</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - chemistry</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</topic><topic>antioxidant</topic><topic>Antioxidants - chemistry</topic><topic>Antioxidants - pharmacology</topic><topic>Antioxidants - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>celastrol</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Pharmacognosy. Homeopathy. Health food</topic><topic>Pharmacology. Drug treatments</topic><topic>Triterpenes - chemistry</topic><topic>Triterpenes - pharmacology</topic><topic>Triterpenes - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Allison, Anthony C.</creatorcontrib><creatorcontrib>Cacabelos, Ramon</creatorcontrib><creatorcontrib>Lombardi, Valter R.M.</creatorcontrib><creatorcontrib>Álvarez, Xoan A.</creatorcontrib><creatorcontrib>Vigo, Carmen</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Progress in neuro-psychopharmacology & biological psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Allison, Anthony C.</au><au>Cacabelos, Ramon</au><au>Lombardi, Valter R.M.</au><au>Álvarez, Xoan A.</au><au>Vigo, Carmen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease</atitle><jtitle>Progress in neuro-psychopharmacology & biological psychiatry</jtitle><addtitle>Prog Neuropsychopharmacol Biol Psychiatry</addtitle><date>2001-10-01</date><risdate>2001</risdate><volume>25</volume><issue>7</issue><spage>1341</spage><epage>1357</epage><pages>1341-1357</pages><issn>0278-5846</issn><eissn>1878-4216</eissn><coden>PNPPD7</coden><abstract>1.
In the brains of patients with Alzheimer's disease (AD) signs of neuronal degeneration are accompanied by markers of microglial activation, inflammation, and oxidant damage. The presence of nitrotyrosine in the cell bodies of neurons in AD suggests that peroxynitrite contributes to the pathogenesis of the disease.
2.
A drug with antioxidant and anti-inflammatory activity may prevent neuronal degeneration in AD. Celastrol, a plant-derived triterpene, has these effects.
3.
In low nanomolar concentrations celastrol was found to suppress the production by human monocytes and macrophages of the pro-inflammatory cytokines TNF-α and IL-1β.
4.
Celastrol also decreased the induced expression of class II MHC molecules by microglia. In macrophage lineage cells and endothelial cells celastrol decreased induced but not constitutive NO production.
5.
Celastrol suppressed adjuvant arthritis in the rat, demonstrating
in vivo anti-inflammatory activity. Low doses of celastrol administered to rats significantly improved their performance in memory, learning and psychomotor activity tests.
6.
The potent antioxidant and anti-inflammatory activities of celastrol, and its effects on cognitive functions, suggest that the drug may be useful to treat neurodegenerative diseases accompanied by inflammation, such as AD.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>11513350</pmid><doi>10.1016/S0278-5846(01)00192-0</doi><tpages>17</tpages></addata></record> |
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| subjects | Alzheimer Disease - drug therapy Alzheimer Disease - metabolism Alzheimer's disease Animals anti-inflammatory Anti-Inflammatory Agents, Non-Steroidal - chemistry Anti-Inflammatory Agents, Non-Steroidal - pharmacology Anti-Inflammatory Agents, Non-Steroidal - therapeutic use antioxidant Antioxidants - chemistry Antioxidants - pharmacology Antioxidants - therapeutic use Biological and medical sciences celastrol General pharmacology Humans Medical sciences Pharmacognosy. Homeopathy. Health food Pharmacology. Drug treatments Triterpenes - chemistry Triterpenes - pharmacology Triterpenes - therapeutic use |
| title | Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease |
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