Paeoniflorin exerts neuroprotective effects against glutamate-induced PC12 cellular cytotoxicity by inhibiting apoptosis
Paeoniflorin (PF) is an active ingredient of Radix Paeoniae, which is known to exert neuroprotective effects. However, the mechanims behind the neuroprotective effects of PF are not yet fully understood. The apoptosis of neurons plays an important role in the cerebral ischemia-induced cascade respon...
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| Veröffentlicht in: | International journal of molecular medicine 2017-09, Vol.40 (3), p.825-833 |
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| creator | Chen, Ahong Wang, Hongyun Zhang, Yuqin Wang, Xiaoying Yu, Lishuang Xu, Wen Xu, Wei Lin, Yu |
| description | Paeoniflorin (PF) is an active ingredient of Radix Paeoniae, which is known to exert neuroprotective effects. However, the mechanims behind the neuroprotective effects of PF are not yet fully understood. The apoptosis of neurons plays an important role in the cerebral ischemia-induced cascade response. This study aimed to investigate neuroprotective effects of PF against glutamate-induced PC12 cellular cytotoxicity and to determine whether these effects are mediated via the inhibition of apoptosis in vitro and the activity of mitochondrial apoptosis-associated proteins in PC12 cells. Exposure of the PC12 cells to glutamate induced cell morphological changes, significantly decreased cell viability and induced apoptosis, with similar results being observed from the Hoechst 33342 staining and Annexin V/PI staining experiments. Glutamate also increased the lactate dehydrogenase release by the PC12 cells. However, treatment with PF prevented these effects. Furthermore, PF inhibited Bax and Bad expression and increased Bcl-2 and Bcl-xL expression; it also decreased the levels of downstream protein (caspase-3 and caspase-9). Collectively, our results indicate that PF protects PC12 cells against glutamate-induced neurotoxicity possibly through the inhibition of the expression of mitochondrial apoptosis-associated proteins. |
| doi_str_mv | 10.3892/ijmm.2017.3076 |
| format | Article |
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However, the mechanims behind the neuroprotective effects of PF are not yet fully understood. The apoptosis of neurons plays an important role in the cerebral ischemia-induced cascade response. This study aimed to investigate neuroprotective effects of PF against glutamate-induced PC12 cellular cytotoxicity and to determine whether these effects are mediated via the inhibition of apoptosis in vitro and the activity of mitochondrial apoptosis-associated proteins in PC12 cells. Exposure of the PC12 cells to glutamate induced cell morphological changes, significantly decreased cell viability and induced apoptosis, with similar results being observed from the Hoechst 33342 staining and Annexin V/PI staining experiments. Glutamate also increased the lactate dehydrogenase release by the PC12 cells. However, treatment with PF prevented these effects. Furthermore, PF inhibited Bax and Bad expression and increased Bcl-2 and Bcl-xL expression; it also decreased the levels of downstream protein (caspase-3 and caspase-9). Collectively, our results indicate that PF protects PC12 cells against glutamate-induced neurotoxicity possibly through the inhibition of the expression of mitochondrial apoptosis-associated proteins.</description><identifier>ISSN: 1107-3756</identifier><identifier>EISSN: 1791-244X</identifier><identifier>DOI: 10.3892/ijmm.2017.3076</identifier><identifier>PMID: 28731183</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Angiosperms ; Animals ; Apoptosis ; Apoptosis - drug effects ; Apoptosis Regulatory Proteins - biosynthesis ; Cellular proteins ; Cytotoxicity ; Cytotoxins - pharmacology ; Dehydrogenases ; Enzymes ; Gene expression ; Gene Expression Regulation - drug effects ; Genetic aspects ; Glucosides - pharmacology ; glutamate ; Glutamic Acid - pharmacology ; Health aspects ; Immunoglobulins ; Ischemia ; Medical research ; Monoterpenes - pharmacology ; Mortality ; Neurologic manifestations ; neuroprotective ; Neuroprotective Agents - pharmacology ; paeoniflorin ; PC12 ; PC12 Cells ; Penicillin ; Permeability ; Plant extracts ; Prevention ; Protein expression ; Proteins ; Rats ; Rodents ; Stroke ; Studies</subject><ispartof>International journal of molecular medicine, 2017-09, Vol.40 (3), p.825-833</ispartof><rights>Copyright: © Chen et al.</rights><rights>COPYRIGHT 2017 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2017</rights><rights>Copyright: © Chen et al. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c584t-9aa564fb0faa4f9f4f6ea14bc8866a40bc0721aba9ed7df6b1e792475948f0f73</citedby><cites>FETCH-LOGICAL-c584t-9aa564fb0faa4f9f4f6ea14bc8866a40bc0721aba9ed7df6b1e792475948f0f73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,5555,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28731183$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Ahong</creatorcontrib><creatorcontrib>Wang, Hongyun</creatorcontrib><creatorcontrib>Zhang, Yuqin</creatorcontrib><creatorcontrib>Wang, Xiaoying</creatorcontrib><creatorcontrib>Yu, Lishuang</creatorcontrib><creatorcontrib>Xu, Wen</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Lin, Yu</creatorcontrib><title>Paeoniflorin exerts neuroprotective effects against glutamate-induced PC12 cellular cytotoxicity by inhibiting apoptosis</title><title>International journal of molecular medicine</title><addtitle>Int J Mol Med</addtitle><description>Paeoniflorin (PF) is an active ingredient of Radix Paeoniae, which is known to exert neuroprotective effects. However, the mechanims behind the neuroprotective effects of PF are not yet fully understood. The apoptosis of neurons plays an important role in the cerebral ischemia-induced cascade response. This study aimed to investigate neuroprotective effects of PF against glutamate-induced PC12 cellular cytotoxicity and to determine whether these effects are mediated via the inhibition of apoptosis in vitro and the activity of mitochondrial apoptosis-associated proteins in PC12 cells. Exposure of the PC12 cells to glutamate induced cell morphological changes, significantly decreased cell viability and induced apoptosis, with similar results being observed from the Hoechst 33342 staining and Annexin V/PI staining experiments. Glutamate also increased the lactate dehydrogenase release by the PC12 cells. However, treatment with PF prevented these effects. Furthermore, PF inhibited Bax and Bad expression and increased Bcl-2 and Bcl-xL expression; it also decreased the levels of downstream protein (caspase-3 and caspase-9). Collectively, our results indicate that PF protects PC12 cells against glutamate-induced neurotoxicity possibly through the inhibition of the expression of mitochondrial apoptosis-associated proteins.</description><subject>Angiosperms</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis Regulatory Proteins - biosynthesis</subject><subject>Cellular proteins</subject><subject>Cytotoxicity</subject><subject>Cytotoxins - pharmacology</subject><subject>Dehydrogenases</subject><subject>Enzymes</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genetic aspects</subject><subject>Glucosides - pharmacology</subject><subject>glutamate</subject><subject>Glutamic Acid - pharmacology</subject><subject>Health aspects</subject><subject>Immunoglobulins</subject><subject>Ischemia</subject><subject>Medical research</subject><subject>Monoterpenes - pharmacology</subject><subject>Mortality</subject><subject>Neurologic manifestations</subject><subject>neuroprotective</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>paeoniflorin</subject><subject>PC12</subject><subject>PC12 Cells</subject><subject>Penicillin</subject><subject>Permeability</subject><subject>Plant extracts</subject><subject>Prevention</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rodents</subject><subject>Stroke</subject><subject>Studies</subject><issn>1107-3756</issn><issn>1791-244X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptksFrHCEUxofS0qRprz0WoZdeZquOjuOlEJa0KQSaQwu9ieM8Ny4zOlUn7P73dUi6pBA8-NDf-_j0fVX1nuBN00n62e2naUMxEZsGi_ZFdU6EJDVl7PfLUhMs6kbw9qx6k9IeY8qZ7F5XZ7QTDSFdc14dbjUE7-wYovMIDhBzQh6WGOYYMpjs7gGBtaVKSO-08ymj3bhkPekMtfPDYmBAt1tCkYFxXEYdkTnmkMPBGZePqD8i5-9c77LzO6TnMOeQXHpbvbJ6TPDucb-ofn29-rm9rm9-fPu-vbypDe9YrqXWvGW2x1ZrZqVltgVNWG-6rm01w73BghLdawmDGGzbExCSMsEl6yy2ormovjzozks_wWDA56hHNUc36XhUQTv1_413d2oX7hXnTMiGF4GPjwIx_FkgZbUPS_TFsyKSUcLx-pMnaqdHUM7bUMTM5JJRl7zMAXMqVzObZ6iyBpicCR6sK-fPNZgYUopgT8YJVmsA1BoAtQZArQEoDR-ePveE_5t4AT49AGnWfnBDSCdmlaoZrnFT447y5i8tZr1b</recordid><startdate>20170901</startdate><enddate>20170901</enddate><creator>Chen, Ahong</creator><creator>Wang, Hongyun</creator><creator>Zhang, Yuqin</creator><creator>Wang, Xiaoying</creator><creator>Yu, Lishuang</creator><creator>Xu, Wen</creator><creator>Xu, Wei</creator><creator>Lin, Yu</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20170901</creationdate><title>Paeoniflorin exerts neuroprotective effects against glutamate-induced PC12 cellular cytotoxicity by inhibiting apoptosis</title><author>Chen, Ahong ; Wang, Hongyun ; Zhang, Yuqin ; Wang, Xiaoying ; Yu, Lishuang ; Xu, Wen ; Xu, Wei ; Lin, Yu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c584t-9aa564fb0faa4f9f4f6ea14bc8866a40bc0721aba9ed7df6b1e792475948f0f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Angiosperms</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis Regulatory Proteins - biosynthesis</topic><topic>Cellular proteins</topic><topic>Cytotoxicity</topic><topic>Cytotoxins - pharmacology</topic><topic>Dehydrogenases</topic><topic>Enzymes</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Genetic aspects</topic><topic>Glucosides - pharmacology</topic><topic>glutamate</topic><topic>Glutamic Acid - pharmacology</topic><topic>Health aspects</topic><topic>Immunoglobulins</topic><topic>Ischemia</topic><topic>Medical research</topic><topic>Monoterpenes - pharmacology</topic><topic>Mortality</topic><topic>Neurologic manifestations</topic><topic>neuroprotective</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>paeoniflorin</topic><topic>PC12</topic><topic>PC12 Cells</topic><topic>Penicillin</topic><topic>Permeability</topic><topic>Plant extracts</topic><topic>Prevention</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rodents</topic><topic>Stroke</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Ahong</creatorcontrib><creatorcontrib>Wang, Hongyun</creatorcontrib><creatorcontrib>Zhang, Yuqin</creatorcontrib><creatorcontrib>Wang, Xiaoying</creatorcontrib><creatorcontrib>Yu, Lishuang</creatorcontrib><creatorcontrib>Xu, Wen</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Lin, Yu</creatorcontrib><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma 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</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Ahong</au><au>Wang, Hongyun</au><au>Zhang, Yuqin</au><au>Wang, Xiaoying</au><au>Yu, Lishuang</au><au>Xu, Wen</au><au>Xu, Wei</au><au>Lin, Yu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Paeoniflorin exerts neuroprotective effects against glutamate-induced PC12 cellular cytotoxicity by inhibiting apoptosis</atitle><jtitle>International journal of molecular medicine</jtitle><addtitle>Int J Mol Med</addtitle><date>2017-09-01</date><risdate>2017</risdate><volume>40</volume><issue>3</issue><spage>825</spage><epage>833</epage><pages>825-833</pages><issn>1107-3756</issn><eissn>1791-244X</eissn><abstract>Paeoniflorin (PF) is an active ingredient of Radix Paeoniae, which is known to exert neuroprotective effects. However, the mechanims behind the neuroprotective effects of PF are not yet fully understood. The apoptosis of neurons plays an important role in the cerebral ischemia-induced cascade response. This study aimed to investigate neuroprotective effects of PF against glutamate-induced PC12 cellular cytotoxicity and to determine whether these effects are mediated via the inhibition of apoptosis in vitro and the activity of mitochondrial apoptosis-associated proteins in PC12 cells. Exposure of the PC12 cells to glutamate induced cell morphological changes, significantly decreased cell viability and induced apoptosis, with similar results being observed from the Hoechst 33342 staining and Annexin V/PI staining experiments. Glutamate also increased the lactate dehydrogenase release by the PC12 cells. However, treatment with PF prevented these effects. Furthermore, PF inhibited Bax and Bad expression and increased Bcl-2 and Bcl-xL expression; it also decreased the levels of downstream protein (caspase-3 and caspase-9). Collectively, our results indicate that PF protects PC12 cells against glutamate-induced neurotoxicity possibly through the inhibition of the expression of mitochondrial apoptosis-associated proteins.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>28731183</pmid><doi>10.3892/ijmm.2017.3076</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Angiosperms Animals Apoptosis Apoptosis - drug effects Apoptosis Regulatory Proteins - biosynthesis Cellular proteins Cytotoxicity Cytotoxins - pharmacology Dehydrogenases Enzymes Gene expression Gene Expression Regulation - drug effects Genetic aspects Glucosides - pharmacology glutamate Glutamic Acid - pharmacology Health aspects Immunoglobulins Ischemia Medical research Monoterpenes - pharmacology Mortality Neurologic manifestations neuroprotective Neuroprotective Agents - pharmacology paeoniflorin PC12 PC12 Cells Penicillin Permeability Plant extracts Prevention Protein expression Proteins Rats Rodents Stroke Studies |
| title | Paeoniflorin exerts neuroprotective effects against glutamate-induced PC12 cellular cytotoxicity by inhibiting apoptosis |
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