Lupeol inhibits LPS-induced neuroinflammation in cerebellar cultures and induces neuroprotection associated to the modulation of astrocyte response and expression of neurotrophic and inflammatory factors
In the central nervous system (CNS), neuroinflammation, especially that modulated by the cell response of astrocytes and microglia, is associated with damage to neurons in neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and, Multiple Sclerosis. Lupeol is a diet...
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| Veröffentlicht in: | International immunopharmacology 2019-05, Vol.70, p.302-312 |
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| creator | Oliveira-Junior, Markley Silva Pereira, Erica Patricia de Amorim, Vanessa Cristina Meira Reis, Luã Tainã Costa do Nascimento, Ravena Pereira da Silva, Victor Diogenes Amaral Costa, Silvia Lima |
| description | In the central nervous system (CNS), neuroinflammation, especially that modulated by the cell response of astrocytes and microglia, is associated with damage to neurons in neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and, Multiple Sclerosis. Lupeol is a dietary triterpene that has demonstrated biological activities as antioxidant. This study investigated the anti-inflammatory and neuroprotective effects of lupeol in an in vitro model of neuroinflammation in primary cerebellar cultures. Cultures were obtained from 6-day-old Wistar rats, subjected to inflammatory damage with lipopolysaccharide (LPS, 1 μg/mL) and treated with lupeol (0.1 μM). We observed, after a 48-hour treatment, through Fluorjade-B staining and immunocytochemistry (ICQ) for βIII-tubulin, that lupeol induced neuroprotection in cultures submitted to inflammatory damage. On the other hand, through ICQ for GFAP, it was possible to observe that lupeol modulated the astrocyte morphology for Bergmann glia-like phenotype and, especially for velate astrocyte-like phenotype, both phenotypes associated with the neuroprotective profile. Moreover, RT-qPCR analysis showed that lupeol induced the down-regulation of the mRNA expression for proinflammatory markers TNF, iNOS and NLRP3, as well as the production of nitric oxide (method of Greiss), which were up-regulated by LPS, and also induced up-regulation of the mRNA expression for arginase and IL-6 mRNA. In addition, lupeol induced up-regulation of mRNA expression for neurotrophins GDNF and NGF and also for the sonic hedgehog–Gli pathway. Together, these results lead to the conclusion that lupeol inhibits neuroinflammation in cerebellar cultures and induces neuroprotection associated with the modulation of astrocyte response and expression of neurotrophic and inflammatory factors. |
| doi_str_mv | 10.1016/j.intimp.2019.02.055 |
| format | Article |
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Lupeol is a dietary triterpene that has demonstrated biological activities as antioxidant. This study investigated the anti-inflammatory and neuroprotective effects of lupeol in an in vitro model of neuroinflammation in primary cerebellar cultures. Cultures were obtained from 6-day-old Wistar rats, subjected to inflammatory damage with lipopolysaccharide (LPS, 1 μg/mL) and treated with lupeol (0.1 μM). We observed, after a 48-hour treatment, through Fluorjade-B staining and immunocytochemistry (ICQ) for βIII-tubulin, that lupeol induced neuroprotection in cultures submitted to inflammatory damage. On the other hand, through ICQ for GFAP, it was possible to observe that lupeol modulated the astrocyte morphology for Bergmann glia-like phenotype and, especially for velate astrocyte-like phenotype, both phenotypes associated with the neuroprotective profile. Moreover, RT-qPCR analysis showed that lupeol induced the down-regulation of the mRNA expression for proinflammatory markers TNF, iNOS and NLRP3, as well as the production of nitric oxide (method of Greiss), which were up-regulated by LPS, and also induced up-regulation of the mRNA expression for arginase and IL-6 mRNA. In addition, lupeol induced up-regulation of mRNA expression for neurotrophins GDNF and NGF and also for the sonic hedgehog–Gli pathway. Together, these results lead to the conclusion that lupeol inhibits neuroinflammation in cerebellar cultures and induces neuroprotection associated with the modulation of astrocyte response and expression of neurotrophic and inflammatory factors.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2019.02.055</identifier><identifier>PMID: 30852286</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Alzheimer's disease ; Antioxidants ; Arginase ; Astrocytes ; Central nervous system ; Cerebellum ; Damage ; Diet ; Gene expression ; Glial cell line-derived neurotrophic factor ; Glial fibrillary acidic protein ; Immunocytochemistry ; Immunomodulation ; Inflammation ; Interleukin 6 ; Lipopolysaccharides ; Lupeol ; Microglia ; Modulation ; Morphology ; Movement disorders ; Multiple sclerosis ; Nerve growth factor ; Neurodegenerative diseases ; Neuroprotection ; Neurotrophic factors ; Nitric oxide ; Nitric-oxide synthase ; Parkinson's disease ; Phenotypes ; SHH/Gli 1 signaling pathway</subject><ispartof>International immunopharmacology, 2019-05, Vol.70, p.302-312</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019. Published by Elsevier B.V.</rights><rights>Copyright Elsevier BV May 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-af0565db160d435c365fdf78c49e002a5576137ccf2dd0555d89641b9f4f7c23</citedby><cites>FETCH-LOGICAL-c502t-af0565db160d435c365fdf78c49e002a5576137ccf2dd0555d89641b9f4f7c23</cites><orcidid>0000-0002-8975-3871</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.intimp.2019.02.055$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30852286$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oliveira-Junior, Markley Silva</creatorcontrib><creatorcontrib>Pereira, Erica Patricia</creatorcontrib><creatorcontrib>de Amorim, Vanessa Cristina Meira</creatorcontrib><creatorcontrib>Reis, Luã Tainã Costa</creatorcontrib><creatorcontrib>do Nascimento, Ravena Pereira</creatorcontrib><creatorcontrib>da Silva, Victor Diogenes Amaral</creatorcontrib><creatorcontrib>Costa, Silvia Lima</creatorcontrib><title>Lupeol inhibits LPS-induced neuroinflammation in cerebellar cultures and induces neuroprotection associated to the modulation of astrocyte response and expression of neurotrophic and inflammatory factors</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>In the central nervous system (CNS), neuroinflammation, especially that modulated by the cell response of astrocytes and microglia, is associated with damage to neurons in neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and, Multiple Sclerosis. Lupeol is a dietary triterpene that has demonstrated biological activities as antioxidant. This study investigated the anti-inflammatory and neuroprotective effects of lupeol in an in vitro model of neuroinflammation in primary cerebellar cultures. Cultures were obtained from 6-day-old Wistar rats, subjected to inflammatory damage with lipopolysaccharide (LPS, 1 μg/mL) and treated with lupeol (0.1 μM). We observed, after a 48-hour treatment, through Fluorjade-B staining and immunocytochemistry (ICQ) for βIII-tubulin, that lupeol induced neuroprotection in cultures submitted to inflammatory damage. On the other hand, through ICQ for GFAP, it was possible to observe that lupeol modulated the astrocyte morphology for Bergmann glia-like phenotype and, especially for velate astrocyte-like phenotype, both phenotypes associated with the neuroprotective profile. Moreover, RT-qPCR analysis showed that lupeol induced the down-regulation of the mRNA expression for proinflammatory markers TNF, iNOS and NLRP3, as well as the production of nitric oxide (method of Greiss), which were up-regulated by LPS, and also induced up-regulation of the mRNA expression for arginase and IL-6 mRNA. In addition, lupeol induced up-regulation of mRNA expression for neurotrophins GDNF and NGF and also for the sonic hedgehog–Gli pathway. Together, these results lead to the conclusion that lupeol inhibits neuroinflammation in cerebellar cultures and induces neuroprotection associated with the modulation of astrocyte response and expression of neurotrophic and inflammatory factors.</description><subject>Alzheimer's disease</subject><subject>Antioxidants</subject><subject>Arginase</subject><subject>Astrocytes</subject><subject>Central nervous system</subject><subject>Cerebellum</subject><subject>Damage</subject><subject>Diet</subject><subject>Gene expression</subject><subject>Glial cell line-derived neurotrophic factor</subject><subject>Glial fibrillary acidic protein</subject><subject>Immunocytochemistry</subject><subject>Immunomodulation</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Lipopolysaccharides</subject><subject>Lupeol</subject><subject>Microglia</subject><subject>Modulation</subject><subject>Morphology</subject><subject>Movement disorders</subject><subject>Multiple sclerosis</subject><subject>Nerve growth factor</subject><subject>Neurodegenerative diseases</subject><subject>Neuroprotection</subject><subject>Neurotrophic factors</subject><subject>Nitric oxide</subject><subject>Nitric-oxide synthase</subject><subject>Parkinson's disease</subject><subject>Phenotypes</subject><subject>SHH/Gli 1 signaling pathway</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kU2r1DAUhoso3g_9ByIBN25ak7Tpx0aQi3qFAQXvPqTJCZOhTWqSyp3f6J_yzHR04cJVvp73PSfnLYpXjFaMsvbdoXI-u3mpOGVDRXlFhXhSXLO-60vWUfEU96LtStG1w1Vxk9KBUrxv2PPiqqa94Lxvr4tfu3WBMBHn9250OZHdt--l82bVYIiHNQbn7aTmWWUXPGJEQ4QRpklFotcprxESUd6QTZQ20RJDBn2WqJSCdiqjXw4k74HMwazT5hcsvucY9DEDQacl-ARnO3hc8Jwu0NkUuWXv9KXapasQj8QqjWt6UTyzakrw8rLeFg-fPj7c3Ze7r5-_3H3YlVpQnktlqWiFGVlLTVMLXbfCGtv1uhmAUq4ETozVndaWG4NDFaYf2oaNg21sp3l9W7zdbPGTP1ZIWc4u6dNEPIQ1Sc4Gyjhta4rom3_QQ1ijx-Yk56zlnWhEj1SzUTqGlCJYuUQ3q3iUjMpT1vIgt6zlKWtJucS2UPb6Yr6OM5i_oj_hIvB-AwCH8dNBlEk78JisixiONMH9v8Jvb7XDHw</recordid><startdate>20190501</startdate><enddate>20190501</enddate><creator>Oliveira-Junior, Markley Silva</creator><creator>Pereira, Erica Patricia</creator><creator>de Amorim, Vanessa Cristina Meira</creator><creator>Reis, Luã Tainã Costa</creator><creator>do Nascimento, Ravena Pereira</creator><creator>da Silva, Victor Diogenes Amaral</creator><creator>Costa, Silvia Lima</creator><general>Elsevier B.V</general><general>Elsevier BV</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8975-3871</orcidid></search><sort><creationdate>20190501</creationdate><title>Lupeol inhibits LPS-induced neuroinflammation in cerebellar cultures and induces neuroprotection associated to the modulation of astrocyte response and expression of neurotrophic and inflammatory factors</title><author>Oliveira-Junior, Markley Silva ; Pereira, Erica Patricia ; de Amorim, Vanessa Cristina Meira ; Reis, Luã Tainã Costa ; do Nascimento, Ravena Pereira ; da Silva, Victor Diogenes Amaral ; Costa, Silvia Lima</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c502t-af0565db160d435c365fdf78c49e002a5576137ccf2dd0555d89641b9f4f7c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Alzheimer's disease</topic><topic>Antioxidants</topic><topic>Arginase</topic><topic>Astrocytes</topic><topic>Central nervous system</topic><topic>Cerebellum</topic><topic>Damage</topic><topic>Diet</topic><topic>Gene expression</topic><topic>Glial cell line-derived neurotrophic factor</topic><topic>Glial fibrillary acidic protein</topic><topic>Immunocytochemistry</topic><topic>Immunomodulation</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Lipopolysaccharides</topic><topic>Lupeol</topic><topic>Microglia</topic><topic>Modulation</topic><topic>Morphology</topic><topic>Movement disorders</topic><topic>Multiple sclerosis</topic><topic>Nerve growth factor</topic><topic>Neurodegenerative diseases</topic><topic>Neuroprotection</topic><topic>Neurotrophic factors</topic><topic>Nitric oxide</topic><topic>Nitric-oxide synthase</topic><topic>Parkinson's disease</topic><topic>Phenotypes</topic><topic>SHH/Gli 1 signaling pathway</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oliveira-Junior, Markley Silva</creatorcontrib><creatorcontrib>Pereira, Erica Patricia</creatorcontrib><creatorcontrib>de Amorim, Vanessa Cristina Meira</creatorcontrib><creatorcontrib>Reis, Luã Tainã Costa</creatorcontrib><creatorcontrib>do Nascimento, Ravena Pereira</creatorcontrib><creatorcontrib>da Silva, Victor Diogenes Amaral</creatorcontrib><creatorcontrib>Costa, Silvia Lima</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Oliveira-Junior, Markley Silva</au><au>Pereira, Erica Patricia</au><au>de Amorim, Vanessa Cristina Meira</au><au>Reis, Luã Tainã Costa</au><au>do Nascimento, Ravena Pereira</au><au>da Silva, Victor Diogenes Amaral</au><au>Costa, Silvia Lima</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lupeol inhibits LPS-induced neuroinflammation in cerebellar cultures and induces neuroprotection associated to the modulation of astrocyte response and expression of neurotrophic and inflammatory factors</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2019-05-01</date><risdate>2019</risdate><volume>70</volume><spage>302</spage><epage>312</epage><pages>302-312</pages><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>In the central nervous system (CNS), neuroinflammation, especially that modulated by the cell response of astrocytes and microglia, is associated with damage to neurons in neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and, Multiple Sclerosis. Lupeol is a dietary triterpene that has demonstrated biological activities as antioxidant. This study investigated the anti-inflammatory and neuroprotective effects of lupeol in an in vitro model of neuroinflammation in primary cerebellar cultures. Cultures were obtained from 6-day-old Wistar rats, subjected to inflammatory damage with lipopolysaccharide (LPS, 1 μg/mL) and treated with lupeol (0.1 μM). We observed, after a 48-hour treatment, through Fluorjade-B staining and immunocytochemistry (ICQ) for βIII-tubulin, that lupeol induced neuroprotection in cultures submitted to inflammatory damage. On the other hand, through ICQ for GFAP, it was possible to observe that lupeol modulated the astrocyte morphology for Bergmann glia-like phenotype and, especially for velate astrocyte-like phenotype, both phenotypes associated with the neuroprotective profile. Moreover, RT-qPCR analysis showed that lupeol induced the down-regulation of the mRNA expression for proinflammatory markers TNF, iNOS and NLRP3, as well as the production of nitric oxide (method of Greiss), which were up-regulated by LPS, and also induced up-regulation of the mRNA expression for arginase and IL-6 mRNA. In addition, lupeol induced up-regulation of mRNA expression for neurotrophins GDNF and NGF and also for the sonic hedgehog–Gli pathway. Together, these results lead to the conclusion that lupeol inhibits neuroinflammation in cerebellar cultures and induces neuroprotection associated with the modulation of astrocyte response and expression of neurotrophic and inflammatory factors.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30852286</pmid><doi>10.1016/j.intimp.2019.02.055</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8975-3871</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Alzheimer's disease Antioxidants Arginase Astrocytes Central nervous system Cerebellum Damage Diet Gene expression Glial cell line-derived neurotrophic factor Glial fibrillary acidic protein Immunocytochemistry Immunomodulation Inflammation Interleukin 6 Lipopolysaccharides Lupeol Microglia Modulation Morphology Movement disorders Multiple sclerosis Nerve growth factor Neurodegenerative diseases Neuroprotection Neurotrophic factors Nitric oxide Nitric-oxide synthase Parkinson's disease Phenotypes SHH/Gli 1 signaling pathway |
| title | Lupeol inhibits LPS-induced neuroinflammation in cerebellar cultures and induces neuroprotection associated to the modulation of astrocyte response and expression of neurotrophic and inflammatory factors |
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