Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans
Compounds that delay aging might also postpone age-related diseases and extend healthspan in humans. Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases....
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| creator | Cai, Wai-Jiao Huang, Jian-Hua Zhang, Su-Qin Wu, Bin Kapahi, Pankaj Zhang, Xin-Min Shen, Zi-Yin |
| description | Compounds that delay aging might also postpone age-related diseases and extend healthspan in humans. Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases. However, whether icariin and its derivatives have the potency of delaying aging remains unclear. Here, we report that icariin and its derivative icariside II extend C. elegans lifespan. Using HPLC, we found high level of icariside II in the animals treated with icariin, suggesting icariside II is the bioactive form in vivo of icariin. Icariside II also increased the thermo and oxidative stress tolerance, slowed locomotion decline in late adulthood and delayed the onset of paralysis mediated by polyQ and Aβ(1-42) proteotoxicity. The lifespan extension effect of icariside II is dependent on the insulin/IGF-1 signaling (IIS) since the daf-16(mu86) and daf-2(e1370) failed to show any lifespan extension upon icariside II treatment. Consistently, icariside II treatment upregulates the expression of DAF-16 targets in the wild-type. Moreover, our data suggests that the heat shock transcription factor HSF-1 has a role in icariside II-dependent lifespan extension further implicating the IIS pathway. In conclusion, we demonstrate a novel natural compound, icariside II as the bioactive form of icariin, extends the healthspan via IIS pathway in C. elegans. |
| doi_str_mv | 10.1371/journal.pone.0028835 |
| format | Article |
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Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases. However, whether icariin and its derivatives have the potency of delaying aging remains unclear. Here, we report that icariin and its derivative icariside II extend C. elegans lifespan. Using HPLC, we found high level of icariside II in the animals treated with icariin, suggesting icariside II is the bioactive form in vivo of icariin. Icariside II also increased the thermo and oxidative stress tolerance, slowed locomotion decline in late adulthood and delayed the onset of paralysis mediated by polyQ and Aβ(1-42) proteotoxicity. The lifespan extension effect of icariside II is dependent on the insulin/IGF-1 signaling (IIS) since the daf-16(mu86) and daf-2(e1370) failed to show any lifespan extension upon icariside II treatment. Consistently, icariside II treatment upregulates the expression of DAF-16 targets in the wild-type. Moreover, our data suggests that the heat shock transcription factor HSF-1 has a role in icariside II-dependent lifespan extension further implicating the IIS pathway. In conclusion, we demonstrate a novel natural compound, icariside II as the bioactive form of icariin, extends the healthspan via IIS pathway in C. elegans.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0028835</identifier><identifier>PMID: 22216122</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Aging ; Aging (natural) ; Animals ; Biological activity ; Biology ; Caenorhabditis elegans ; Caenorhabditis elegans - metabolism ; Caenorhabditis elegans Proteins - metabolism ; Chemistry ; Chinese medicine ; Derivatives ; Drosophila ; Drug dosages ; Epimedium ; Flavonoids ; Flavonoids - pharmacology ; Gene expression ; Genetics ; Heat shock ; Heat shock factors ; Heat shock proteins ; High performance liquid chromatography ; Hospitals ; Insects ; Insulin ; Insulin - metabolism ; Insulin-like growth factor I ; Insulin-Like Growth Factor I - metabolism ; Insulin-like growth factors ; Life span ; Liquid chromatography ; Localization ; Locomotion ; Longevity ; Mammals ; Medicine ; Mutation ; Nematodes ; Oxidative stress ; Paralysis ; Plant extracts ; Polyglutamine ; Signaling ; Transcription factors ; Worms</subject><ispartof>PloS one, 2011-12, Vol.6 (12), p.e28835-e28835</ispartof><rights>2011 Cai et al.</rights><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Cai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Cai et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-cee0dad96033efb2d48ea5cbb5bb14746c0d84a5d1c2384689d8c870e49251743</citedby><cites>FETCH-LOGICAL-c757t-cee0dad96033efb2d48ea5cbb5bb14746c0d84a5d1c2384689d8c870e49251743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244416/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244416/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22216122$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Blagosklonny, Mikhail V.</contributor><creatorcontrib>Cai, Wai-Jiao</creatorcontrib><creatorcontrib>Huang, Jian-Hua</creatorcontrib><creatorcontrib>Zhang, Su-Qin</creatorcontrib><creatorcontrib>Wu, Bin</creatorcontrib><creatorcontrib>Kapahi, Pankaj</creatorcontrib><creatorcontrib>Zhang, Xin-Min</creatorcontrib><creatorcontrib>Shen, Zi-Yin</creatorcontrib><title>Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Compounds that delay aging might also postpone age-related diseases and extend healthspan in humans. Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases. However, whether icariin and its derivatives have the potency of delaying aging remains unclear. Here, we report that icariin and its derivative icariside II extend C. elegans lifespan. Using HPLC, we found high level of icariside II in the animals treated with icariin, suggesting icariside II is the bioactive form in vivo of icariin. Icariside II also increased the thermo and oxidative stress tolerance, slowed locomotion decline in late adulthood and delayed the onset of paralysis mediated by polyQ and Aβ(1-42) proteotoxicity. The lifespan extension effect of icariside II is dependent on the insulin/IGF-1 signaling (IIS) since the daf-16(mu86) and daf-2(e1370) failed to show any lifespan extension upon icariside II treatment. Consistently, icariside II treatment upregulates the expression of DAF-16 targets in the wild-type. Moreover, our data suggests that the heat shock transcription factor HSF-1 has a role in icariside II-dependent lifespan extension further implicating the IIS pathway. In conclusion, we demonstrate a novel natural compound, icariside II as the bioactive form of icariin, extends the healthspan via IIS pathway in C. elegans.</description><subject>Age</subject><subject>Aging</subject><subject>Aging (natural)</subject><subject>Animals</subject><subject>Biological activity</subject><subject>Biology</subject><subject>Caenorhabditis elegans</subject><subject>Caenorhabditis elegans - metabolism</subject><subject>Caenorhabditis elegans Proteins - metabolism</subject><subject>Chemistry</subject><subject>Chinese medicine</subject><subject>Derivatives</subject><subject>Drosophila</subject><subject>Drug dosages</subject><subject>Epimedium</subject><subject>Flavonoids</subject><subject>Flavonoids - pharmacology</subject><subject>Gene expression</subject><subject>Genetics</subject><subject>Heat shock</subject><subject>Heat shock factors</subject><subject>Heat shock proteins</subject><subject>High performance liquid chromatography</subject><subject>Hospitals</subject><subject>Insects</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin-like growth factor I</subject><subject>Insulin-Like Growth Factor I - metabolism</subject><subject>Insulin-like growth factors</subject><subject>Life span</subject><subject>Liquid chromatography</subject><subject>Localization</subject><subject>Locomotion</subject><subject>Longevity</subject><subject>Mammals</subject><subject>Medicine</subject><subject>Mutation</subject><subject>Nematodes</subject><subject>Oxidative stress</subject><subject>Paralysis</subject><subject>Plant extracts</subject><subject>Polyglutamine</subject><subject>Signaling</subject><subject>Transcription factors</subject><subject>Worms</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99r2zAQx83YWLts_8HYDIONPSTVL9vyy6CUtTMUCvv1Ks7SOVFwpNSys_W_n7K4JR59GHqQuPvc96TTXZK8pmRBeUHP1n7oHLSLrXe4IIRJybMnySktOZvnjPCnR-eT5EUIa0IyLvP8eXLCGKM5Zew0gUpDZ61LwZnU9iE12Nkd9HaHqd27gjWYVlWKv3uMyAqh7VdhCy7dWUitC0Nr3Vl1dTmn6Rb61S-4i9b0YpFii0tw4WXyrIE24KtxnyU_Lj9_v_gyv765qi7Or-e6yIp-rhGJAVPmhHNsamaERMh0XWd1TUUhck2MFJAZqhmXIpelkVoWBEXJMloIPkveHnS3rQ9qrE5QlNP4VkGi7CypDoTxsFbbzm6gu1MerPpr8N1SQddb3aIijdZNIWqGOcTkWDdlURZ1wwRnvI4VnSWfxmxDvUGj0fUdtBPRqcfZlVr6neJMCEHzKPBhFOj87YChVxsbNLYtOPRDUCUVnJCCyki--4d8_HEjtYR4f-saH9PqvaY6F0UuM8nZPuviESougxurYyc1NtonAR8nAZHpYyssYQhBVd--_j9783PKvj9ix67y7dBb78IUFAdQdz6EDpuHGlOi9oNwXw21HwQ1DkIMe3P8Pw9B953P_wD8JAHt</recordid><startdate>20111221</startdate><enddate>20111221</enddate><creator>Cai, Wai-Jiao</creator><creator>Huang, Jian-Hua</creator><creator>Zhang, Su-Qin</creator><creator>Wu, Bin</creator><creator>Kapahi, Pankaj</creator><creator>Zhang, Xin-Min</creator><creator>Shen, Zi-Yin</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20111221</creationdate><title>Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans</title><author>Cai, Wai-Jiao ; Huang, Jian-Hua ; Zhang, Su-Qin ; Wu, Bin ; Kapahi, Pankaj ; Zhang, Xin-Min ; Shen, Zi-Yin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-cee0dad96033efb2d48ea5cbb5bb14746c0d84a5d1c2384689d8c870e49251743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Age</topic><topic>Aging</topic><topic>Aging (natural)</topic><topic>Animals</topic><topic>Biological activity</topic><topic>Biology</topic><topic>Caenorhabditis elegans</topic><topic>Caenorhabditis elegans - metabolism</topic><topic>Caenorhabditis elegans Proteins - metabolism</topic><topic>Chemistry</topic><topic>Chinese medicine</topic><topic>Derivatives</topic><topic>Drosophila</topic><topic>Drug dosages</topic><topic>Epimedium</topic><topic>Flavonoids</topic><topic>Flavonoids - pharmacology</topic><topic>Gene expression</topic><topic>Genetics</topic><topic>Heat shock</topic><topic>Heat shock factors</topic><topic>Heat shock proteins</topic><topic>High performance liquid chromatography</topic><topic>Hospitals</topic><topic>Insects</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Insulin-like growth factor I</topic><topic>Insulin-Like Growth Factor I - metabolism</topic><topic>Insulin-like growth factors</topic><topic>Life span</topic><topic>Liquid chromatography</topic><topic>Localization</topic><topic>Locomotion</topic><topic>Longevity</topic><topic>Mammals</topic><topic>Medicine</topic><topic>Mutation</topic><topic>Nematodes</topic><topic>Oxidative stress</topic><topic>Paralysis</topic><topic>Plant extracts</topic><topic>Polyglutamine</topic><topic>Signaling</topic><topic>Transcription factors</topic><topic>Worms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cai, Wai-Jiao</creatorcontrib><creatorcontrib>Huang, Jian-Hua</creatorcontrib><creatorcontrib>Zhang, Su-Qin</creatorcontrib><creatorcontrib>Wu, Bin</creatorcontrib><creatorcontrib>Kapahi, Pankaj</creatorcontrib><creatorcontrib>Zhang, Xin-Min</creatorcontrib><creatorcontrib>Shen, Zi-Yin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cai, Wai-Jiao</au><au>Huang, Jian-Hua</au><au>Zhang, Su-Qin</au><au>Wu, Bin</au><au>Kapahi, Pankaj</au><au>Zhang, Xin-Min</au><au>Shen, Zi-Yin</au><au>Blagosklonny, Mikhail V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-12-21</date><risdate>2011</risdate><volume>6</volume><issue>12</issue><spage>e28835</spage><epage>e28835</epage><pages>e28835-e28835</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Compounds that delay aging might also postpone age-related diseases and extend healthspan in humans. Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases. However, whether icariin and its derivatives have the potency of delaying aging remains unclear. Here, we report that icariin and its derivative icariside II extend C. elegans lifespan. Using HPLC, we found high level of icariside II in the animals treated with icariin, suggesting icariside II is the bioactive form in vivo of icariin. Icariside II also increased the thermo and oxidative stress tolerance, slowed locomotion decline in late adulthood and delayed the onset of paralysis mediated by polyQ and Aβ(1-42) proteotoxicity. The lifespan extension effect of icariside II is dependent on the insulin/IGF-1 signaling (IIS) since the daf-16(mu86) and daf-2(e1370) failed to show any lifespan extension upon icariside II treatment. Consistently, icariside II treatment upregulates the expression of DAF-16 targets in the wild-type. Moreover, our data suggests that the heat shock transcription factor HSF-1 has a role in icariside II-dependent lifespan extension further implicating the IIS pathway. In conclusion, we demonstrate a novel natural compound, icariside II as the bioactive form of icariin, extends the healthspan via IIS pathway in C. elegans.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22216122</pmid><doi>10.1371/journal.pone.0028835</doi><tpages>e28835</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Age Aging Aging (natural) Animals Biological activity Biology Caenorhabditis elegans Caenorhabditis elegans - metabolism Caenorhabditis elegans Proteins - metabolism Chemistry Chinese medicine Derivatives Drosophila Drug dosages Epimedium Flavonoids Flavonoids - pharmacology Gene expression Genetics Heat shock Heat shock factors Heat shock proteins High performance liquid chromatography Hospitals Insects Insulin Insulin - metabolism Insulin-like growth factor I Insulin-Like Growth Factor I - metabolism Insulin-like growth factors Life span Liquid chromatography Localization Locomotion Longevity Mammals Medicine Mutation Nematodes Oxidative stress Paralysis Plant extracts Polyglutamine Signaling Transcription factors Worms |
| title | Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T01%3A46%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Icariin%20and%20its%20derivative%20icariside%20II%20extend%20healthspan%20via%20insulin/IGF-1%20pathway%20in%20C.%20elegans&rft.jtitle=PloS%20one&rft.au=Cai,%20Wai-Jiao&rft.date=2011-12-21&rft.volume=6&rft.issue=12&rft.spage=e28835&rft.epage=e28835&rft.pages=e28835-e28835&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0028835&rft_dat=%3Cgale_plos_%3EA476858326%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1312164003&rft_id=info:pmid/22216122&rft_galeid=A476858326&rft_doaj_id=oai_doaj_org_article_0fccf74b2e6a474ebf9797bf24323b20&rfr_iscdi=true |