Phloretin attenuates behavior deficits and neuroinflammatory response in MPTP induced Parkinson's disease in mice
Neuroinflammation is one of the significant neuropathological conditions in Parkinson's disease (PD) which is due to microglial and astrocytes activation leads to progressive dopaminergic neuronal loss. To date, Current PD drugs offers only symptomatic relief with adverse effects and lack of ab...
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Veröffentlicht in: | Life sciences (1973) 2019-09, Vol.232, p.116600-116600, Article 116600 |
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description | Neuroinflammation is one of the significant neuropathological conditions in Parkinson's disease (PD) which is due to microglial and astrocytes activation leads to progressive dopaminergic neuronal loss. To date, Current PD drugs offers only symptomatic relief with adverse effects and lack of ability to prevent the progression of neurodegeneration. Therefore, a better approach to develop a multi potent drug of natural origin would be beneficial in managing the disease. Therefore, the present study aimed to investigate the neuroprotective and anti-inflammatory effects of PHL by exploring its neuroprotective mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) induced PD in mice. MPTP intoxication in mice cause motor abnormalities, decreased dopamine (DA) levels, reduced tyrosine hydroxylase (TH) enzyme protein expression and inflammation which were effectively restored by PHL. Moreover gliotic specific inflammatory markers like glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1 (Iba-1), iNOS and COX-2 were found to be expressed more in MPTP intoxicated mice, Further the levels of proinflammatory cytokines like IL-β, IL-6, and TNF-α were significantly upregulated in MPTP intoxicated mice, these deleterious responses were diminished to extend neuroprotection by PHL treatment. Our findings strongly suggest PHL as a potent therapeutic agent in treating PD. |
doi_str_mv | 10.1016/j.lfs.2019.116600 |
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To date, Current PD drugs offers only symptomatic relief with adverse effects and lack of ability to prevent the progression of neurodegeneration. Therefore, a better approach to develop a multi potent drug of natural origin would be beneficial in managing the disease. Therefore, the present study aimed to investigate the neuroprotective and anti-inflammatory effects of PHL by exploring its neuroprotective mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) induced PD in mice. MPTP intoxication in mice cause motor abnormalities, decreased dopamine (DA) levels, reduced tyrosine hydroxylase (TH) enzyme protein expression and inflammation which were effectively restored by PHL. Moreover gliotic specific inflammatory markers like glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1 (Iba-1), iNOS and COX-2 were found to be expressed more in MPTP intoxicated mice, Further the levels of proinflammatory cytokines like IL-β, IL-6, and TNF-α were significantly upregulated in MPTP intoxicated mice, these deleterious responses were diminished to extend neuroprotection by PHL treatment. Our findings strongly suggest PHL as a potent therapeutic agent in treating PD.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2019.116600</identifier><identifier>PMID: 31251998</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Abnormalities ; Astrocytes ; Calcium ; Chemical compounds ; Cyclooxygenase-2 ; Cytokines ; Disease control ; Dopamine ; Dopamine receptors ; Glial fibrillary acidic protein ; Hydroxylase ; Inflammation ; Interleukin 6 ; Intoxication ; Mice ; Movement disorders ; MPTP ; Neurodegeneration ; Neurodegenerative diseases ; Neuroinflammation ; Neuroprotection ; Nitric-oxide synthase ; Parkinson's disease ; Pharmacology ; PHL ; Proteins ; Pyridines ; Tumor necrosis factor-α ; Tyrosine ; Tyrosine 3-monooxygenase</subject><ispartof>Life sciences (1973), 2019-09, Vol.232, p.116600-116600, Article 116600</ispartof><rights>2019</rights><rights>Copyright © 2019. Published by Elsevier Inc.</rights><rights>Copyright Elsevier BV Sep 1, 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-2be92486b63c0f737a9f30590dc24f6704bdd2dc73d7b1ad092526a51a9abc723</citedby><cites>FETCH-LOGICAL-c381t-2be92486b63c0f737a9f30590dc24f6704bdd2dc73d7b1ad092526a51a9abc723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0024320519305260$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31251998$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Gejuan</creatorcontrib><creatorcontrib>Yang, Geqiang</creatorcontrib><creatorcontrib>Liu, Jian</creatorcontrib><title>Phloretin attenuates behavior deficits and neuroinflammatory response in MPTP induced Parkinson's disease in mice</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Neuroinflammation is one of the significant neuropathological conditions in Parkinson's disease (PD) which is due to microglial and astrocytes activation leads to progressive dopaminergic neuronal loss. To date, Current PD drugs offers only symptomatic relief with adverse effects and lack of ability to prevent the progression of neurodegeneration. Therefore, a better approach to develop a multi potent drug of natural origin would be beneficial in managing the disease. Therefore, the present study aimed to investigate the neuroprotective and anti-inflammatory effects of PHL by exploring its neuroprotective mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) induced PD in mice. MPTP intoxication in mice cause motor abnormalities, decreased dopamine (DA) levels, reduced tyrosine hydroxylase (TH) enzyme protein expression and inflammation which were effectively restored by PHL. Moreover gliotic specific inflammatory markers like glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1 (Iba-1), iNOS and COX-2 were found to be expressed more in MPTP intoxicated mice, Further the levels of proinflammatory cytokines like IL-β, IL-6, and TNF-α were significantly upregulated in MPTP intoxicated mice, these deleterious responses were diminished to extend neuroprotection by PHL treatment. Our findings strongly suggest PHL as a potent therapeutic agent in treating PD.</description><subject>Abnormalities</subject><subject>Astrocytes</subject><subject>Calcium</subject><subject>Chemical compounds</subject><subject>Cyclooxygenase-2</subject><subject>Cytokines</subject><subject>Disease control</subject><subject>Dopamine</subject><subject>Dopamine receptors</subject><subject>Glial fibrillary acidic protein</subject><subject>Hydroxylase</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Intoxication</subject><subject>Mice</subject><subject>Movement disorders</subject><subject>MPTP</subject><subject>Neurodegeneration</subject><subject>Neurodegenerative diseases</subject><subject>Neuroinflammation</subject><subject>Neuroprotection</subject><subject>Nitric-oxide synthase</subject><subject>Parkinson's disease</subject><subject>Pharmacology</subject><subject>PHL</subject><subject>Proteins</subject><subject>Pyridines</subject><subject>Tumor necrosis factor-α</subject><subject>Tyrosine</subject><subject>Tyrosine 3-monooxygenase</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kU1v1DAURS0EokPhB7BBlljAJsOzHceJWFUVX1IRsyhry7FfVA-JPbWdSv33uEphwYLV25x79XQPIa8Z7Bmw7sNxP095z4ENe8a6DuAJ2bFeDQ10gj0lOwDeNoKDPCMvcj4CgJRKPCdngnHJhqHfkdvDzRwTFh-oKQXDagpmOuKNufMxUYeTt75kaoKjAdcUfZhmsyymxHRPE-ZTDBlpjX8_XB_qdatFRw8m_fIhx_AuU-czmo1ZvMWX5Nlk5oyvHu85-fn50_Xl1-bqx5dvlxdXjRU9Kw0fceBt342dsDApocwwCZADOMvbqVPQjs5xZ5VwamTGwcAl74xkZjCjVVyck_db7ynF2xVz0YvPFufZBIxr1pzLOpNoW1HRt_-gx7imUL-rVK8kCNa3lWIbZVPMOeGkT8kvJt1rBvrBhz7q6kM_-NCbj5p589i8jgu6v4k_AirwcQOwTnHnMelsPYa6oU9oi3bR_6f-N1aQm5E</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Zhang, Gejuan</creator><creator>Yang, Geqiang</creator><creator>Liu, Jian</creator><general>Elsevier Inc</general><general>Elsevier BV</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20190901</creationdate><title>Phloretin attenuates behavior deficits and neuroinflammatory response in MPTP induced Parkinson's disease in mice</title><author>Zhang, Gejuan ; Yang, Geqiang ; Liu, Jian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-2be92486b63c0f737a9f30590dc24f6704bdd2dc73d7b1ad092526a51a9abc723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Abnormalities</topic><topic>Astrocytes</topic><topic>Calcium</topic><topic>Chemical compounds</topic><topic>Cyclooxygenase-2</topic><topic>Cytokines</topic><topic>Disease control</topic><topic>Dopamine</topic><topic>Dopamine receptors</topic><topic>Glial fibrillary acidic protein</topic><topic>Hydroxylase</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Intoxication</topic><topic>Mice</topic><topic>Movement disorders</topic><topic>MPTP</topic><topic>Neurodegeneration</topic><topic>Neurodegenerative diseases</topic><topic>Neuroinflammation</topic><topic>Neuroprotection</topic><topic>Nitric-oxide synthase</topic><topic>Parkinson's disease</topic><topic>Pharmacology</topic><topic>PHL</topic><topic>Proteins</topic><topic>Pyridines</topic><topic>Tumor necrosis factor-α</topic><topic>Tyrosine</topic><topic>Tyrosine 3-monooxygenase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Gejuan</creatorcontrib><creatorcontrib>Yang, Geqiang</creatorcontrib><creatorcontrib>Liu, Jian</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences 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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Gejuan</au><au>Yang, Geqiang</au><au>Liu, Jian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phloretin attenuates behavior deficits and neuroinflammatory response in MPTP induced Parkinson's disease in mice</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>232</volume><spage>116600</spage><epage>116600</epage><pages>116600-116600</pages><artnum>116600</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Neuroinflammation is one of the significant neuropathological conditions in Parkinson's disease (PD) which is due to microglial and astrocytes activation leads to progressive dopaminergic neuronal loss. To date, Current PD drugs offers only symptomatic relief with adverse effects and lack of ability to prevent the progression of neurodegeneration. Therefore, a better approach to develop a multi potent drug of natural origin would be beneficial in managing the disease. Therefore, the present study aimed to investigate the neuroprotective and anti-inflammatory effects of PHL by exploring its neuroprotective mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) induced PD in mice. MPTP intoxication in mice cause motor abnormalities, decreased dopamine (DA) levels, reduced tyrosine hydroxylase (TH) enzyme protein expression and inflammation which were effectively restored by PHL. Moreover gliotic specific inflammatory markers like glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1 (Iba-1), iNOS and COX-2 were found to be expressed more in MPTP intoxicated mice, Further the levels of proinflammatory cytokines like IL-β, IL-6, and TNF-α were significantly upregulated in MPTP intoxicated mice, these deleterious responses were diminished to extend neuroprotection by PHL treatment. Our findings strongly suggest PHL as a potent therapeutic agent in treating PD.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>31251998</pmid><doi>10.1016/j.lfs.2019.116600</doi><tpages>1</tpages></addata></record> |
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subjects | Abnormalities Astrocytes Calcium Chemical compounds Cyclooxygenase-2 Cytokines Disease control Dopamine Dopamine receptors Glial fibrillary acidic protein Hydroxylase Inflammation Interleukin 6 Intoxication Mice Movement disorders MPTP Neurodegeneration Neurodegenerative diseases Neuroinflammation Neuroprotection Nitric-oxide synthase Parkinson's disease Pharmacology PHL Proteins Pyridines Tumor necrosis factor-α Tyrosine Tyrosine 3-monooxygenase |
title | Phloretin attenuates behavior deficits and neuroinflammatory response in MPTP induced Parkinson's disease in mice |
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