Neuroprotective properties of ethanolic extract of Citrus unshiu Markovich peel through NADPH oxidase 2 inhibition in chemotherapy‐induced neuropathic pain animal model
The present study aimed to determine the antioxidant effect of Citrus unshiu Markovich (CUM) extract in neuronal cell lines under oxidative stress and to investigate the effect of chemotherapy‐induced peripheral neuropathy (CIPN) on the nociceptive response in a preclinical mice model. We tested the...
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| Veröffentlicht in: | Phytotherapy research 2021-12, Vol.35 (12), p.6918-6931 |
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| creator | Jang, Aelee Choi, Go‐Eun Kim, Yoo‐Jeong Lee, Gil‐Hyun Hyun, Kyung‐Yae |
| description | The present study aimed to determine the antioxidant effect of Citrus unshiu Markovich (CUM) extract in neuronal cell lines under oxidative stress and to investigate the effect of chemotherapy‐induced peripheral neuropathy (CIPN) on the nociceptive response in a preclinical mice model. We tested the inhibition of H2O2 in Neuro2A cells treated with CUM. Experimental animals were treated with oxaliplatin to induce CINP, and then administered oral CUM for 4 weeks in order to observe the effect of CUM. Animals were evaluated weekly for thermal hyperalgesia and digital motor nerve conduction velocity (NCV). Lumbar dorsal root ganglia (DRG) isolated from each animal were evaluated through immunochemical and western blot analysis for nerve damage, inflammatory response, and expression of redox signaling factors. The main mechanisms were determined to be decreased inducible nitric oxide synthase (iNOS) production due to the inhibition of NADPH oxidase 2 (NOX2). To determine the functional role of NOX2 in CINP, we administrated CUM into NOX2‐deficient mice with neuropathic pain. Therefore, we suggest that CUM controls the expression levels of inflammatory factors in CINP via NOX2 inactivation. This study demonstrated that a complementary medicine such as CUM might be a potential novel therapeutic agent for the treatment of CINP. |
| doi_str_mv | 10.1002/ptr.7304 |
| format | Article |
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We tested the inhibition of H2O2 in Neuro2A cells treated with CUM. Experimental animals were treated with oxaliplatin to induce CINP, and then administered oral CUM for 4 weeks in order to observe the effect of CUM. Animals were evaluated weekly for thermal hyperalgesia and digital motor nerve conduction velocity (NCV). Lumbar dorsal root ganglia (DRG) isolated from each animal were evaluated through immunochemical and western blot analysis for nerve damage, inflammatory response, and expression of redox signaling factors. The main mechanisms were determined to be decreased inducible nitric oxide synthase (iNOS) production due to the inhibition of NADPH oxidase 2 (NOX2). To determine the functional role of NOX2 in CINP, we administrated CUM into NOX2‐deficient mice with neuropathic pain. Therefore, we suggest that CUM controls the expression levels of inflammatory factors in CINP via NOX2 inactivation. This study demonstrated that a complementary medicine such as CUM might be a potential novel therapeutic agent for the treatment of CINP.</description><identifier>ISSN: 0951-418X</identifier><identifier>EISSN: 1099-1573</identifier><identifier>DOI: 10.1002/ptr.7304</identifier><identifier>PMID: 34818693</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animal models ; Animals ; Antineoplastic Agents - adverse effects ; Antioxidants ; Cell lines ; Chemical compounds ; Chemotherapy ; chemotherapy‐induced peripheral neuropathy ; Citrus - chemistry ; Citrus unshiu ; Citrus unshiu Markovich ; CYBB protein ; Dorsal root ganglia ; Ganglia ; Hydrogen peroxide ; Hyperalgesia ; Hyperalgesia - chemically induced ; Hyperalgesia - drug therapy ; Inactivation ; Inflammation ; Inflammatory response ; Mice ; Models, Animal ; NAD(P)H oxidase ; NADPH oxidase 2 ; NADPH Oxidase 2 - antagonists & inhibitors ; Nerve conduction ; nerve conduction velocity ; Neuralgia - chemically induced ; Neuralgia - drug therapy ; Neuroprotection ; Neuroprotective Agents - pharmacology ; Nitric oxide ; Nitric-oxide synthase ; Oxaliplatin ; Oxidase ; Oxidative stress ; Pain ; Pain perception ; Peripheral neuropathy ; Pharmacology ; Plant Extracts - pharmacology ; reactive oxygen species</subject><ispartof>Phytotherapy research, 2021-12, Vol.35 (12), p.6918-6931</ispartof><rights>2021 John Wiley & Sons Ltd.</rights><rights>2021 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3494-7bf463300ab6a7c4f545eb2743a8bb9a68e452d27fdfd9697ba923c038dbf0ba3</citedby><cites>FETCH-LOGICAL-c3494-7bf463300ab6a7c4f545eb2743a8bb9a68e452d27fdfd9697ba923c038dbf0ba3</cites><orcidid>0000-0003-0800-2919</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fptr.7304$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fptr.7304$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34818693$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jang, Aelee</creatorcontrib><creatorcontrib>Choi, Go‐Eun</creatorcontrib><creatorcontrib>Kim, Yoo‐Jeong</creatorcontrib><creatorcontrib>Lee, Gil‐Hyun</creatorcontrib><creatorcontrib>Hyun, Kyung‐Yae</creatorcontrib><title>Neuroprotective properties of ethanolic extract of Citrus unshiu Markovich peel through NADPH oxidase 2 inhibition in chemotherapy‐induced neuropathic pain animal model</title><title>Phytotherapy research</title><addtitle>Phytother Res</addtitle><description>The present study aimed to determine the antioxidant effect of Citrus unshiu Markovich (CUM) extract in neuronal cell lines under oxidative stress and to investigate the effect of chemotherapy‐induced peripheral neuropathy (CIPN) on the nociceptive response in a preclinical mice model. We tested the inhibition of H2O2 in Neuro2A cells treated with CUM. Experimental animals were treated with oxaliplatin to induce CINP, and then administered oral CUM for 4 weeks in order to observe the effect of CUM. Animals were evaluated weekly for thermal hyperalgesia and digital motor nerve conduction velocity (NCV). Lumbar dorsal root ganglia (DRG) isolated from each animal were evaluated through immunochemical and western blot analysis for nerve damage, inflammatory response, and expression of redox signaling factors. The main mechanisms were determined to be decreased inducible nitric oxide synthase (iNOS) production due to the inhibition of NADPH oxidase 2 (NOX2). To determine the functional role of NOX2 in CINP, we administrated CUM into NOX2‐deficient mice with neuropathic pain. Therefore, we suggest that CUM controls the expression levels of inflammatory factors in CINP via NOX2 inactivation. This study demonstrated that a complementary medicine such as CUM might be a potential novel therapeutic agent for the treatment of CINP.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antioxidants</subject><subject>Cell lines</subject><subject>Chemical compounds</subject><subject>Chemotherapy</subject><subject>chemotherapy‐induced peripheral neuropathy</subject><subject>Citrus - chemistry</subject><subject>Citrus unshiu</subject><subject>Citrus unshiu Markovich</subject><subject>CYBB protein</subject><subject>Dorsal root ganglia</subject><subject>Ganglia</subject><subject>Hydrogen peroxide</subject><subject>Hyperalgesia</subject><subject>Hyperalgesia - chemically induced</subject><subject>Hyperalgesia - drug therapy</subject><subject>Inactivation</subject><subject>Inflammation</subject><subject>Inflammatory response</subject><subject>Mice</subject><subject>Models, Animal</subject><subject>NAD(P)H oxidase</subject><subject>NADPH oxidase 2</subject><subject>NADPH Oxidase 2 - antagonists & inhibitors</subject><subject>Nerve conduction</subject><subject>nerve conduction velocity</subject><subject>Neuralgia - chemically induced</subject><subject>Neuralgia - drug therapy</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Nitric oxide</subject><subject>Nitric-oxide synthase</subject><subject>Oxaliplatin</subject><subject>Oxidase</subject><subject>Oxidative stress</subject><subject>Pain</subject><subject>Pain perception</subject><subject>Peripheral neuropathy</subject><subject>Pharmacology</subject><subject>Plant Extracts - pharmacology</subject><subject>reactive oxygen species</subject><issn>0951-418X</issn><issn>1099-1573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kdtqFTEUhoModrcKPoEEvPFm2pzmkMuy1VZoa5EK3g1JZo2TOjMZc6jddz6Cz-Fj9Uma3VYFwau1WHx8ayU_Qi8o2aeEsIMl-v2aE_EIrSiRsqBlzR-jFZElLQRtPu-g3RAuCSGSEfEU7XDR0KaSfIV-nUHybvEugon2CnBuF_DRQsCuxxAHNbvRGgzX0SsTt8O1jT4FnOYw2IRPlf_qrqwZ8AIw4jh4l74M-Ozwzfkxdte2UwEww3YerLbRujm32AwwuTiAV8vm5sdPO3fJQIfnu2NUHPLCRWVOzXZSI55cB-Mz9KRXY4DnD3UPfXr39mJ9XJx8OHq_PjwpDBdSFLXuRcU5IUpXqjaiL0UJmtWCq0ZrqaoGRMk6Vvdd38lK1lpJxg3hTad7ohXfQ6_vvfkrviUIsZ1sMDCOagaXQssqwipBK15n9NU_6KVLfs7XZYoysd3K_wqNdyF46NvF52f5TUtJu82vzfm12_wy-vJBmPQE3R_wd2AZKO6B73aEzX9F7fnFxzvhLeU7qTU</recordid><startdate>202112</startdate><enddate>202112</enddate><creator>Jang, Aelee</creator><creator>Choi, Go‐Eun</creator><creator>Kim, Yoo‐Jeong</creator><creator>Lee, Gil‐Hyun</creator><creator>Hyun, Kyung‐Yae</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Subscription Services, Inc</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>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0800-2919</orcidid></search><sort><creationdate>202112</creationdate><title>Neuroprotective properties of ethanolic extract of Citrus unshiu Markovich peel through NADPH oxidase 2 inhibition in chemotherapy‐induced neuropathic pain animal model</title><author>Jang, Aelee ; Choi, Go‐Eun ; Kim, Yoo‐Jeong ; Lee, Gil‐Hyun ; Hyun, Kyung‐Yae</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3494-7bf463300ab6a7c4f545eb2743a8bb9a68e452d27fdfd9697ba923c038dbf0ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antioxidants</topic><topic>Cell lines</topic><topic>Chemical compounds</topic><topic>Chemotherapy</topic><topic>chemotherapy‐induced peripheral neuropathy</topic><topic>Citrus - chemistry</topic><topic>Citrus unshiu</topic><topic>Citrus unshiu Markovich</topic><topic>CYBB protein</topic><topic>Dorsal root ganglia</topic><topic>Ganglia</topic><topic>Hydrogen peroxide</topic><topic>Hyperalgesia</topic><topic>Hyperalgesia - chemically induced</topic><topic>Hyperalgesia - drug therapy</topic><topic>Inactivation</topic><topic>Inflammation</topic><topic>Inflammatory response</topic><topic>Mice</topic><topic>Models, Animal</topic><topic>NAD(P)H oxidase</topic><topic>NADPH oxidase 2</topic><topic>NADPH Oxidase 2 - antagonists & inhibitors</topic><topic>Nerve conduction</topic><topic>nerve conduction velocity</topic><topic>Neuralgia - chemically induced</topic><topic>Neuralgia - drug therapy</topic><topic>Neuroprotection</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Nitric oxide</topic><topic>Nitric-oxide synthase</topic><topic>Oxaliplatin</topic><topic>Oxidase</topic><topic>Oxidative stress</topic><topic>Pain</topic><topic>Pain perception</topic><topic>Peripheral neuropathy</topic><topic>Pharmacology</topic><topic>Plant Extracts - pharmacology</topic><topic>reactive oxygen species</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jang, Aelee</creatorcontrib><creatorcontrib>Choi, Go‐Eun</creatorcontrib><creatorcontrib>Kim, Yoo‐Jeong</creatorcontrib><creatorcontrib>Lee, Gil‐Hyun</creatorcontrib><creatorcontrib>Hyun, Kyung‐Yae</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Phytotherapy research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jang, Aelee</au><au>Choi, Go‐Eun</au><au>Kim, Yoo‐Jeong</au><au>Lee, Gil‐Hyun</au><au>Hyun, Kyung‐Yae</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotective properties of ethanolic extract of Citrus unshiu Markovich peel through NADPH oxidase 2 inhibition in chemotherapy‐induced neuropathic pain animal model</atitle><jtitle>Phytotherapy research</jtitle><addtitle>Phytother Res</addtitle><date>2021-12</date><risdate>2021</risdate><volume>35</volume><issue>12</issue><spage>6918</spage><epage>6931</epage><pages>6918-6931</pages><issn>0951-418X</issn><eissn>1099-1573</eissn><abstract>The present study aimed to determine the antioxidant effect of Citrus unshiu Markovich (CUM) extract in neuronal cell lines under oxidative stress and to investigate the effect of chemotherapy‐induced peripheral neuropathy (CIPN) on the nociceptive response in a preclinical mice model. We tested the inhibition of H2O2 in Neuro2A cells treated with CUM. Experimental animals were treated with oxaliplatin to induce CINP, and then administered oral CUM for 4 weeks in order to observe the effect of CUM. Animals were evaluated weekly for thermal hyperalgesia and digital motor nerve conduction velocity (NCV). Lumbar dorsal root ganglia (DRG) isolated from each animal were evaluated through immunochemical and western blot analysis for nerve damage, inflammatory response, and expression of redox signaling factors. The main mechanisms were determined to be decreased inducible nitric oxide synthase (iNOS) production due to the inhibition of NADPH oxidase 2 (NOX2). To determine the functional role of NOX2 in CINP, we administrated CUM into NOX2‐deficient mice with neuropathic pain. Therefore, we suggest that CUM controls the expression levels of inflammatory factors in CINP via NOX2 inactivation. This study demonstrated that a complementary medicine such as CUM might be a potential novel therapeutic agent for the treatment of CINP.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>34818693</pmid><doi>10.1002/ptr.7304</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-0800-2919</orcidid></addata></record> |
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| subjects | Animal models Animals Antineoplastic Agents - adverse effects Antioxidants Cell lines Chemical compounds Chemotherapy chemotherapy‐induced peripheral neuropathy Citrus - chemistry Citrus unshiu Citrus unshiu Markovich CYBB protein Dorsal root ganglia Ganglia Hydrogen peroxide Hyperalgesia Hyperalgesia - chemically induced Hyperalgesia - drug therapy Inactivation Inflammation Inflammatory response Mice Models, Animal NAD(P)H oxidase NADPH oxidase 2 NADPH Oxidase 2 - antagonists & inhibitors Nerve conduction nerve conduction velocity Neuralgia - chemically induced Neuralgia - drug therapy Neuroprotection Neuroprotective Agents - pharmacology Nitric oxide Nitric-oxide synthase Oxaliplatin Oxidase Oxidative stress Pain Pain perception Peripheral neuropathy Pharmacology Plant Extracts - pharmacology reactive oxygen species |
| title | Neuroprotective properties of ethanolic extract of Citrus unshiu Markovich peel through NADPH oxidase 2 inhibition in chemotherapy‐induced neuropathic pain animal model |
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