Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease
Objective Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease‐modifying treatment for PD exists to date. Therefore, the id...
Gespeichert in:
| Veröffentlicht in: | CNS neuroscience & therapeutics 2024-04, Vol.30 (4), p.e14515-n/a |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | n/a |
|---|---|
| container_issue | 4 |
| container_start_page | e14515 |
| container_title | CNS neuroscience & therapeutics |
| container_volume | 30 |
| creator | Zhu, Feng‐Dan Wang, Bin‐Ding Qin, Da‐Lian Su, Xiao‐Hui Yu, Lu Wu, Jian‐Ming Law, Betty Yuen‐Kwan Guo, Min‐Song Yu, Chong‐Lin Zhou, Xiao‐Gang Wu, An‐Guo |
| description | Objective
Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease‐modifying treatment for PD exists to date. Therefore, the identification of novel therapeutic agents with neuroprotective properties is of utmost importance. Here, we aimed to investigate the potential neuroprotective effects of Carpesii fructus extract (CFE) in both cellular and Caenorhabditis elegans (C. elegans) models of PD.
Methods
The neuroprotective effect of CFE in H2O2‐ or 6‐OHDA‐induced PC‐12 cells and α‐synuclein‐overexpressing PC‐12 cells were investigated by determining the cell viability, mitochondrial damage, reactive oxygen species (ROS) production, apoptosis, and α‐synuclein expression. In NL5901, BZ555, and N2 worms, the expression of α‐synuclein, motive ability, the viability of dopaminergic neurons, lifespan, and aging‐related phenotypes were investigated. The signaling pathway was detected by Western blotting and validated by employing small inhibitors and RNAi bacteria.
Results
In cellular models of PD, CFE significantly attenuated H2O2‐ or 6‐OHDA‐induced toxicity, as evidenced by increased cell viability and reduced apoptosis rate. In addition, CFE treatment suppressed ROS generation and restored mitochondrial membrane potential, highlighting its potential as a mitochondrial protective agent. Furthermore, CFE reduced the expression of α‐synuclein in wide type (WT)‐, A53T‐, A30P‐, or E46K‐α‐synuclein‐overexpressing PC‐12 cells. Our further findings reveal that CFE administration reduced α‐synuclein expression and improved its induced locomotor deficits in NL5901 worms, protected dopaminergic neurons against 6‐OHDA‐induced degeneration in BZ555 worms, extended lifespan, delayed aging‐related phenotypes, and enhanced the ability of stress resistance in N2 worms. Mechanistic studies suggest that the neuroprotective effects of CFE may involve the modulation of the MAPK signaling pathway, including ERK, JNK, and p38, whereas the interference of these pathways attenuated the neuroprotective effect of CFE in vitro and in vivo.
Conclusion
Overall, our study highlights the potential therapeutic value of CFE as a neuroprotective agent in the context of PD. Furthermore, elucidation of the active compounds of CFE will provide valuable insights for the development of novel therapeutic strategies for PD.
Carpesii fruc |
| doi_str_mv | 10.1111/cns.14515 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11017466</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3086332239</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4445-acd9568ae0a43384873fbcf2c52dc56a6545de720976f49c96cf54697804ec1c3</originalsourceid><addsrcrecordid>eNp1kU1rFTEUhoNYbK0u_AMScGG7uG0y-ZjJSmSotVBUUNchN3PSmzo3uebMVLvxt5t660UFszkH8vBwXl5CnnF2wus79QlPuFRcPSAHvFVqoYw0D3e7YPvkMeI1Y7rpTPeI7IvWMFWhA_Kjd2UDGCMNZfbTjBS-T8X5qc5VXMYJaYK55E3JE_gp3gCFEOqGNCbqYRzn0RXq0kB7BymXlVsOcYrVM8KVS0jXeYARaQ70gytfYsKcXiIdIoJDeEL2ghsRnt7PQ_L5zdmn_u3i8v35Rf_6cuGllGrh_GCU7hwwJ4XoZNeKsPSh8aoZvNJOK6kGaBtmWh2k8Ub7oKQ2bcckeO7FIXm19W7m5RoGD6mGHO2mxLUrtza7aP_-SXFlr_KN5ZzxVmpdDUf3hpK_zoCTXUe8y-8S5Blt03VSt0pIXtEX_6DXeS6p5rOCdVqIphGmUsdbypeMWCDsruHM3tVqa632V62Vff7n-Tvyd48VON0C3-IIt_832f7dx63yJ5Lgr3E</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3086332239</pqid></control><display><type>article</type><title>Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley-Blackwell Open Access Titles</source><source>PubMed Central</source><creator>Zhu, Feng‐Dan ; Wang, Bin‐Ding ; Qin, Da‐Lian ; Su, Xiao‐Hui ; Yu, Lu ; Wu, Jian‐Ming ; Law, Betty Yuen‐Kwan ; Guo, Min‐Song ; Yu, Chong‐Lin ; Zhou, Xiao‐Gang ; Wu, An‐Guo</creator><creatorcontrib>Zhu, Feng‐Dan ; Wang, Bin‐Ding ; Qin, Da‐Lian ; Su, Xiao‐Hui ; Yu, Lu ; Wu, Jian‐Ming ; Law, Betty Yuen‐Kwan ; Guo, Min‐Song ; Yu, Chong‐Lin ; Zhou, Xiao‐Gang ; Wu, An‐Guo</creatorcontrib><description>Objective
Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease‐modifying treatment for PD exists to date. Therefore, the identification of novel therapeutic agents with neuroprotective properties is of utmost importance. Here, we aimed to investigate the potential neuroprotective effects of Carpesii fructus extract (CFE) in both cellular and Caenorhabditis elegans (C. elegans) models of PD.
Methods
The neuroprotective effect of CFE in H2O2‐ or 6‐OHDA‐induced PC‐12 cells and α‐synuclein‐overexpressing PC‐12 cells were investigated by determining the cell viability, mitochondrial damage, reactive oxygen species (ROS) production, apoptosis, and α‐synuclein expression. In NL5901, BZ555, and N2 worms, the expression of α‐synuclein, motive ability, the viability of dopaminergic neurons, lifespan, and aging‐related phenotypes were investigated. The signaling pathway was detected by Western blotting and validated by employing small inhibitors and RNAi bacteria.
Results
In cellular models of PD, CFE significantly attenuated H2O2‐ or 6‐OHDA‐induced toxicity, as evidenced by increased cell viability and reduced apoptosis rate. In addition, CFE treatment suppressed ROS generation and restored mitochondrial membrane potential, highlighting its potential as a mitochondrial protective agent. Furthermore, CFE reduced the expression of α‐synuclein in wide type (WT)‐, A53T‐, A30P‐, or E46K‐α‐synuclein‐overexpressing PC‐12 cells. Our further findings reveal that CFE administration reduced α‐synuclein expression and improved its induced locomotor deficits in NL5901 worms, protected dopaminergic neurons against 6‐OHDA‐induced degeneration in BZ555 worms, extended lifespan, delayed aging‐related phenotypes, and enhanced the ability of stress resistance in N2 worms. Mechanistic studies suggest that the neuroprotective effects of CFE may involve the modulation of the MAPK signaling pathway, including ERK, JNK, and p38, whereas the interference of these pathways attenuated the neuroprotective effect of CFE in vitro and in vivo.
Conclusion
Overall, our study highlights the potential therapeutic value of CFE as a neuroprotective agent in the context of PD. Furthermore, elucidation of the active compounds of CFE will provide valuable insights for the development of novel therapeutic strategies for PD.
Carpesii fructus extract (CFE) attenuates H2O2‐ or 6‐OHDA‐induced toxicity and reduce α‐synuclein to inhibit ROS production and restore MMP in PC‐12 cells and Caenorhabditis elegans, resulting in the improvement of dopaminergic neurons and motor ability in PD. These effects are involved the regulation of MAPK signaling pathway.</description><identifier>ISSN: 1755-5930</identifier><identifier>EISSN: 1755-5949</identifier><identifier>DOI: 10.1111/cns.14515</identifier><identifier>PMID: 37905594</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>6‐OHDA ; Aging ; alpha-Synuclein - metabolism ; Animals ; Antibodies ; Apoptosis ; Caenorhabditis elegans ; Caenorhabditis elegans - genetics ; Caenorhabditis elegans - metabolism ; Carpesii fructus extract ; Cell viability ; Disease Models, Animal ; Dopamine receptors ; Dopaminergic Neurons - metabolism ; Hydrogen peroxide ; Hydrogen Peroxide - metabolism ; Hydrogen Peroxide - toxicity ; Life span ; MAP kinase ; MAPK pathway ; Membrane potential ; Mitochondria ; Movement disorders ; Natural products ; Nematodes ; Neurodegeneration ; Neurodegenerative diseases ; Neuromodulation ; Neurons ; Neuroprotection ; Neuroprotective Agents - metabolism ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; Neurotoxicity ; Original ; Oxidative stress ; Oxidopamine - toxicity ; Parkinson Disease - drug therapy ; Parkinson Disease - metabolism ; Parkinson's disease ; Pathogenesis ; PC‐12 cells ; Penicillin ; Phenotypes ; Plasmids ; Proteins ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; RNA-mediated interference ; Signal transduction ; Solvents ; Substantia nigra ; Synuclein ; Western blotting ; α‐Synuclein</subject><ispartof>CNS neuroscience & therapeutics, 2024-04, Vol.30 (4), p.e14515-n/a</ispartof><rights>2023 The Authors. published by John Wiley & Sons Ltd.</rights><rights>2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.</rights><rights>2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4445-acd9568ae0a43384873fbcf2c52dc56a6545de720976f49c96cf54697804ec1c3</citedby><cites>FETCH-LOGICAL-c4445-acd9568ae0a43384873fbcf2c52dc56a6545de720976f49c96cf54697804ec1c3</cites><orcidid>0000-0002-9850-7576</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017466/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017466/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,1414,11545,27907,27908,45557,45558,46035,46459,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37905594$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Feng‐Dan</creatorcontrib><creatorcontrib>Wang, Bin‐Ding</creatorcontrib><creatorcontrib>Qin, Da‐Lian</creatorcontrib><creatorcontrib>Su, Xiao‐Hui</creatorcontrib><creatorcontrib>Yu, Lu</creatorcontrib><creatorcontrib>Wu, Jian‐Ming</creatorcontrib><creatorcontrib>Law, Betty Yuen‐Kwan</creatorcontrib><creatorcontrib>Guo, Min‐Song</creatorcontrib><creatorcontrib>Yu, Chong‐Lin</creatorcontrib><creatorcontrib>Zhou, Xiao‐Gang</creatorcontrib><creatorcontrib>Wu, An‐Guo</creatorcontrib><title>Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease</title><title>CNS neuroscience & therapeutics</title><addtitle>CNS Neurosci Ther</addtitle><description>Objective
Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease‐modifying treatment for PD exists to date. Therefore, the identification of novel therapeutic agents with neuroprotective properties is of utmost importance. Here, we aimed to investigate the potential neuroprotective effects of Carpesii fructus extract (CFE) in both cellular and Caenorhabditis elegans (C. elegans) models of PD.
Methods
The neuroprotective effect of CFE in H2O2‐ or 6‐OHDA‐induced PC‐12 cells and α‐synuclein‐overexpressing PC‐12 cells were investigated by determining the cell viability, mitochondrial damage, reactive oxygen species (ROS) production, apoptosis, and α‐synuclein expression. In NL5901, BZ555, and N2 worms, the expression of α‐synuclein, motive ability, the viability of dopaminergic neurons, lifespan, and aging‐related phenotypes were investigated. The signaling pathway was detected by Western blotting and validated by employing small inhibitors and RNAi bacteria.
Results
In cellular models of PD, CFE significantly attenuated H2O2‐ or 6‐OHDA‐induced toxicity, as evidenced by increased cell viability and reduced apoptosis rate. In addition, CFE treatment suppressed ROS generation and restored mitochondrial membrane potential, highlighting its potential as a mitochondrial protective agent. Furthermore, CFE reduced the expression of α‐synuclein in wide type (WT)‐, A53T‐, A30P‐, or E46K‐α‐synuclein‐overexpressing PC‐12 cells. Our further findings reveal that CFE administration reduced α‐synuclein expression and improved its induced locomotor deficits in NL5901 worms, protected dopaminergic neurons against 6‐OHDA‐induced degeneration in BZ555 worms, extended lifespan, delayed aging‐related phenotypes, and enhanced the ability of stress resistance in N2 worms. Mechanistic studies suggest that the neuroprotective effects of CFE may involve the modulation of the MAPK signaling pathway, including ERK, JNK, and p38, whereas the interference of these pathways attenuated the neuroprotective effect of CFE in vitro and in vivo.
Conclusion
Overall, our study highlights the potential therapeutic value of CFE as a neuroprotective agent in the context of PD. Furthermore, elucidation of the active compounds of CFE will provide valuable insights for the development of novel therapeutic strategies for PD.
Carpesii fructus extract (CFE) attenuates H2O2‐ or 6‐OHDA‐induced toxicity and reduce α‐synuclein to inhibit ROS production and restore MMP in PC‐12 cells and Caenorhabditis elegans, resulting in the improvement of dopaminergic neurons and motor ability in PD. These effects are involved the regulation of MAPK signaling pathway.</description><subject>6‐OHDA</subject><subject>Aging</subject><subject>alpha-Synuclein - metabolism</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Caenorhabditis elegans</subject><subject>Caenorhabditis elegans - genetics</subject><subject>Caenorhabditis elegans - metabolism</subject><subject>Carpesii fructus extract</subject><subject>Cell viability</subject><subject>Disease Models, Animal</subject><subject>Dopamine receptors</subject><subject>Dopaminergic Neurons - metabolism</subject><subject>Hydrogen peroxide</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Hydrogen Peroxide - toxicity</subject><subject>Life span</subject><subject>MAP kinase</subject><subject>MAPK pathway</subject><subject>Membrane potential</subject><subject>Mitochondria</subject><subject>Movement disorders</subject><subject>Natural products</subject><subject>Nematodes</subject><subject>Neurodegeneration</subject><subject>Neurodegenerative diseases</subject><subject>Neuromodulation</subject><subject>Neurons</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - metabolism</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Neurotoxicity</subject><subject>Original</subject><subject>Oxidative stress</subject><subject>Oxidopamine - toxicity</subject><subject>Parkinson Disease - drug therapy</subject><subject>Parkinson Disease - metabolism</subject><subject>Parkinson's disease</subject><subject>Pathogenesis</subject><subject>PC‐12 cells</subject><subject>Penicillin</subject><subject>Phenotypes</subject><subject>Plasmids</subject><subject>Proteins</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>RNA-mediated interference</subject><subject>Signal transduction</subject><subject>Solvents</subject><subject>Substantia nigra</subject><subject>Synuclein</subject><subject>Western blotting</subject><subject>α‐Synuclein</subject><issn>1755-5930</issn><issn>1755-5949</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kU1rFTEUhoNYbK0u_AMScGG7uG0y-ZjJSmSotVBUUNchN3PSmzo3uebMVLvxt5t660UFszkH8vBwXl5CnnF2wus79QlPuFRcPSAHvFVqoYw0D3e7YPvkMeI1Y7rpTPeI7IvWMFWhA_Kjd2UDGCMNZfbTjBS-T8X5qc5VXMYJaYK55E3JE_gp3gCFEOqGNCbqYRzn0RXq0kB7BymXlVsOcYrVM8KVS0jXeYARaQ70gytfYsKcXiIdIoJDeEL2ghsRnt7PQ_L5zdmn_u3i8v35Rf_6cuGllGrh_GCU7hwwJ4XoZNeKsPSh8aoZvNJOK6kGaBtmWh2k8Ub7oKQ2bcckeO7FIXm19W7m5RoGD6mGHO2mxLUrtza7aP_-SXFlr_KN5ZzxVmpdDUf3hpK_zoCTXUe8y-8S5Blt03VSt0pIXtEX_6DXeS6p5rOCdVqIphGmUsdbypeMWCDsruHM3tVqa632V62Vff7n-Tvyd48VON0C3-IIt_832f7dx63yJ5Lgr3E</recordid><startdate>202404</startdate><enddate>202404</enddate><creator>Zhu, Feng‐Dan</creator><creator>Wang, Bin‐Ding</creator><creator>Qin, Da‐Lian</creator><creator>Su, Xiao‐Hui</creator><creator>Yu, Lu</creator><creator>Wu, Jian‐Ming</creator><creator>Law, Betty Yuen‐Kwan</creator><creator>Guo, Min‐Song</creator><creator>Yu, Chong‐Lin</creator><creator>Zhou, Xiao‐Gang</creator><creator>Wu, An‐Guo</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9850-7576</orcidid></search><sort><creationdate>202404</creationdate><title>Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease</title><author>Zhu, Feng‐Dan ; Wang, Bin‐Ding ; Qin, Da‐Lian ; Su, Xiao‐Hui ; Yu, Lu ; Wu, Jian‐Ming ; Law, Betty Yuen‐Kwan ; Guo, Min‐Song ; Yu, Chong‐Lin ; Zhou, Xiao‐Gang ; Wu, An‐Guo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4445-acd9568ae0a43384873fbcf2c52dc56a6545de720976f49c96cf54697804ec1c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>6‐OHDA</topic><topic>Aging</topic><topic>alpha-Synuclein - metabolism</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Caenorhabditis elegans</topic><topic>Caenorhabditis elegans - genetics</topic><topic>Caenorhabditis elegans - metabolism</topic><topic>Carpesii fructus extract</topic><topic>Cell viability</topic><topic>Disease Models, Animal</topic><topic>Dopamine receptors</topic><topic>Dopaminergic Neurons - metabolism</topic><topic>Hydrogen peroxide</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>Hydrogen Peroxide - toxicity</topic><topic>Life span</topic><topic>MAP kinase</topic><topic>MAPK pathway</topic><topic>Membrane potential</topic><topic>Mitochondria</topic><topic>Movement disorders</topic><topic>Natural products</topic><topic>Nematodes</topic><topic>Neurodegeneration</topic><topic>Neurodegenerative diseases</topic><topic>Neuromodulation</topic><topic>Neurons</topic><topic>Neuroprotection</topic><topic>Neuroprotective Agents - metabolism</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Neurotoxicity</topic><topic>Original</topic><topic>Oxidative stress</topic><topic>Oxidopamine - toxicity</topic><topic>Parkinson Disease - drug therapy</topic><topic>Parkinson Disease - metabolism</topic><topic>Parkinson's disease</topic><topic>Pathogenesis</topic><topic>PC‐12 cells</topic><topic>Penicillin</topic><topic>Phenotypes</topic><topic>Plasmids</topic><topic>Proteins</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>RNA-mediated interference</topic><topic>Signal transduction</topic><topic>Solvents</topic><topic>Substantia nigra</topic><topic>Synuclein</topic><topic>Western blotting</topic><topic>α‐Synuclein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Feng‐Dan</creatorcontrib><creatorcontrib>Wang, Bin‐Ding</creatorcontrib><creatorcontrib>Qin, Da‐Lian</creatorcontrib><creatorcontrib>Su, Xiao‐Hui</creatorcontrib><creatorcontrib>Yu, Lu</creatorcontrib><creatorcontrib>Wu, Jian‐Ming</creatorcontrib><creatorcontrib>Law, Betty Yuen‐Kwan</creatorcontrib><creatorcontrib>Guo, Min‐Song</creatorcontrib><creatorcontrib>Yu, Chong‐Lin</creatorcontrib><creatorcontrib>Zhou, Xiao‐Gang</creatorcontrib><creatorcontrib>Wu, An‐Guo</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>CNS neuroscience & therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Feng‐Dan</au><au>Wang, Bin‐Ding</au><au>Qin, Da‐Lian</au><au>Su, Xiao‐Hui</au><au>Yu, Lu</au><au>Wu, Jian‐Ming</au><au>Law, Betty Yuen‐Kwan</au><au>Guo, Min‐Song</au><au>Yu, Chong‐Lin</au><au>Zhou, Xiao‐Gang</au><au>Wu, An‐Guo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease</atitle><jtitle>CNS neuroscience & therapeutics</jtitle><addtitle>CNS Neurosci Ther</addtitle><date>2024-04</date><risdate>2024</risdate><volume>30</volume><issue>4</issue><spage>e14515</spage><epage>n/a</epage><pages>e14515-n/a</pages><issn>1755-5930</issn><eissn>1755-5949</eissn><abstract>Objective
Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease‐modifying treatment for PD exists to date. Therefore, the identification of novel therapeutic agents with neuroprotective properties is of utmost importance. Here, we aimed to investigate the potential neuroprotective effects of Carpesii fructus extract (CFE) in both cellular and Caenorhabditis elegans (C. elegans) models of PD.
Methods
The neuroprotective effect of CFE in H2O2‐ or 6‐OHDA‐induced PC‐12 cells and α‐synuclein‐overexpressing PC‐12 cells were investigated by determining the cell viability, mitochondrial damage, reactive oxygen species (ROS) production, apoptosis, and α‐synuclein expression. In NL5901, BZ555, and N2 worms, the expression of α‐synuclein, motive ability, the viability of dopaminergic neurons, lifespan, and aging‐related phenotypes were investigated. The signaling pathway was detected by Western blotting and validated by employing small inhibitors and RNAi bacteria.
Results
In cellular models of PD, CFE significantly attenuated H2O2‐ or 6‐OHDA‐induced toxicity, as evidenced by increased cell viability and reduced apoptosis rate. In addition, CFE treatment suppressed ROS generation and restored mitochondrial membrane potential, highlighting its potential as a mitochondrial protective agent. Furthermore, CFE reduced the expression of α‐synuclein in wide type (WT)‐, A53T‐, A30P‐, or E46K‐α‐synuclein‐overexpressing PC‐12 cells. Our further findings reveal that CFE administration reduced α‐synuclein expression and improved its induced locomotor deficits in NL5901 worms, protected dopaminergic neurons against 6‐OHDA‐induced degeneration in BZ555 worms, extended lifespan, delayed aging‐related phenotypes, and enhanced the ability of stress resistance in N2 worms. Mechanistic studies suggest that the neuroprotective effects of CFE may involve the modulation of the MAPK signaling pathway, including ERK, JNK, and p38, whereas the interference of these pathways attenuated the neuroprotective effect of CFE in vitro and in vivo.
Conclusion
Overall, our study highlights the potential therapeutic value of CFE as a neuroprotective agent in the context of PD. Furthermore, elucidation of the active compounds of CFE will provide valuable insights for the development of novel therapeutic strategies for PD.
Carpesii fructus extract (CFE) attenuates H2O2‐ or 6‐OHDA‐induced toxicity and reduce α‐synuclein to inhibit ROS production and restore MMP in PC‐12 cells and Caenorhabditis elegans, resulting in the improvement of dopaminergic neurons and motor ability in PD. These effects are involved the regulation of MAPK signaling pathway.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>37905594</pmid><doi>10.1111/cns.14515</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-9850-7576</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1755-5930 |
| ispartof | CNS neuroscience & therapeutics, 2024-04, Vol.30 (4), p.e14515-n/a |
| issn | 1755-5930 1755-5949 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11017466 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley-Blackwell Open Access Titles; PubMed Central |
| subjects | 6‐OHDA Aging alpha-Synuclein - metabolism Animals Antibodies Apoptosis Caenorhabditis elegans Caenorhabditis elegans - genetics Caenorhabditis elegans - metabolism Carpesii fructus extract Cell viability Disease Models, Animal Dopamine receptors Dopaminergic Neurons - metabolism Hydrogen peroxide Hydrogen Peroxide - metabolism Hydrogen Peroxide - toxicity Life span MAP kinase MAPK pathway Membrane potential Mitochondria Movement disorders Natural products Nematodes Neurodegeneration Neurodegenerative diseases Neuromodulation Neurons Neuroprotection Neuroprotective Agents - metabolism Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Neurotoxicity Original Oxidative stress Oxidopamine - toxicity Parkinson Disease - drug therapy Parkinson Disease - metabolism Parkinson's disease Pathogenesis PC‐12 cells Penicillin Phenotypes Plasmids Proteins Reactive oxygen species Reactive Oxygen Species - metabolism RNA-mediated interference Signal transduction Solvents Substantia nigra Synuclein Western blotting α‐Synuclein |
| title | Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T10%3A36%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Carpesii%20fructus%20extract%20exhibits%20neuroprotective%20effects%20in%20cellular%20and%20Caenorhabditis%20elegans%20models%20of%20Parkinson's%20disease&rft.jtitle=CNS%20neuroscience%20&%20therapeutics&rft.au=Zhu,%20Feng%E2%80%90Dan&rft.date=2024-04&rft.volume=30&rft.issue=4&rft.spage=e14515&rft.epage=n/a&rft.pages=e14515-n/a&rft.issn=1755-5930&rft.eissn=1755-5949&rft_id=info:doi/10.1111/cns.14515&rft_dat=%3Cproquest_pubme%3E3086332239%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3086332239&rft_id=info:pmid/37905594&rfr_iscdi=true |