Enantiospecific pharmacokinetics of isoxanthohumol and its metabolite 8-prenylnaringenin in the rat
Scope Isoxanthohumol (IX) is a bioactive dietary prenylflavanone found in hops (Humulus lupulus L.), beer and nutraceuticals. IX is formed in vivo by xanthohumol and is a prodrug of 8‐prenylnaringenin (8PN). IX and 8PN chirality has largely been ignored in the literature due to lack of enantiospecif...
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| Veröffentlicht in: | Molecular nutrition & food research 2015-09, Vol.59 (9), p.1674-1689 |
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| creator | Martinez, Stephanie E. Davies, Neal M. |
| description | Scope
Isoxanthohumol (IX) is a bioactive dietary prenylflavanone found in hops (Humulus lupulus L.), beer and nutraceuticals. IX is formed in vivo by xanthohumol and is a prodrug of 8‐prenylnaringenin (8PN). IX and 8PN chirality has largely been ignored in the literature due to lack of enantiospecific bioanalytical methods. No single dose pharmacokinetic study of IX exists in the literature for any species. This study elucidates the enantiospecific pharmacokinetics of IX in rats and monitors the appearance of 8PN following intravenous and oral administration of ±IX.
Methods and results
After intravenous (10 mg/kg) or oral (100 mg/kg) administration of ±IX to rats, serum, and urine were collected for 120 h and analyzed for IX and 8PN. Both were found as aglycones and glucuronide conjugates and displayed multiple peaking in serum suggestive of enterohepatic recycling. IX is primarily excreted through nonrenal routes. S‐8PN was found excreted in the urine in greater amounts than R‐8PN. Bioavailability was determined to be ∼4–5% for IX.
Conclusion
Further enantiospecific pharmacokinetics of IX, subsequent 8PN and other metabolites are warranted along with continued enantiospecific bioactivity studies, especially in relation to gut microbial metabolism of IX and subsequent formation of 8PN. |
| doi_str_mv | 10.1002/mnfr.201500118 |
| format | Article |
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Isoxanthohumol (IX) is a bioactive dietary prenylflavanone found in hops (Humulus lupulus L.), beer and nutraceuticals. IX is formed in vivo by xanthohumol and is a prodrug of 8‐prenylnaringenin (8PN). IX and 8PN chirality has largely been ignored in the literature due to lack of enantiospecific bioanalytical methods. No single dose pharmacokinetic study of IX exists in the literature for any species. This study elucidates the enantiospecific pharmacokinetics of IX in rats and monitors the appearance of 8PN following intravenous and oral administration of ±IX.
Methods and results
After intravenous (10 mg/kg) or oral (100 mg/kg) administration of ±IX to rats, serum, and urine were collected for 120 h and analyzed for IX and 8PN. Both were found as aglycones and glucuronide conjugates and displayed multiple peaking in serum suggestive of enterohepatic recycling. IX is primarily excreted through nonrenal routes. S‐8PN was found excreted in the urine in greater amounts than R‐8PN. Bioavailability was determined to be ∼4–5% for IX.
Conclusion
Further enantiospecific pharmacokinetics of IX, subsequent 8PN and other metabolites are warranted along with continued enantiospecific bioactivity studies, especially in relation to gut microbial metabolism of IX and subsequent formation of 8PN.</description><identifier>ISSN: 1613-4125</identifier><identifier>EISSN: 1613-4133</identifier><identifier>DOI: 10.1002/mnfr.201500118</identifier><identifier>PMID: 26079861</identifier><language>eng</language><publisher>Germany: Blackwell Publishing Ltd</publisher><subject>Administration, Intravenous ; Administration, Oral ; Animals ; Biological Availability ; Chiral ; Circular Dichroism ; Dietary Supplements ; Flavanones - blood ; Flavanones - pharmacokinetics ; Flavanones - urine ; Flavonoids ; Glucuronides - blood ; Humulus - chemistry ; Isoxanthohumol ; LC-MS ; Male ; Pharmacokinetics ; Plant Extracts - blood ; Plant Extracts - pharmacokinetics ; Plant Extracts - urine ; Rats ; Rats, Sprague-Dawley ; Xanthones - blood ; Xanthones - pharmacokinetics ; Xanthones - urine</subject><ispartof>Molecular nutrition & food research, 2015-09, Vol.59 (9), p.1674-1689</ispartof><rights>2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5148-8e57045155c5dd2f4fee1a50488dc6eee0612550c4d0126e2120d0a49c872cd73</citedby><cites>FETCH-LOGICAL-c5148-8e57045155c5dd2f4fee1a50488dc6eee0612550c4d0126e2120d0a49c872cd73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmnfr.201500118$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmnfr.201500118$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26079861$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martinez, Stephanie E.</creatorcontrib><creatorcontrib>Davies, Neal M.</creatorcontrib><title>Enantiospecific pharmacokinetics of isoxanthohumol and its metabolite 8-prenylnaringenin in the rat</title><title>Molecular nutrition & food research</title><addtitle>Mol. Nutr. Food Res</addtitle><description>Scope
Isoxanthohumol (IX) is a bioactive dietary prenylflavanone found in hops (Humulus lupulus L.), beer and nutraceuticals. IX is formed in vivo by xanthohumol and is a prodrug of 8‐prenylnaringenin (8PN). IX and 8PN chirality has largely been ignored in the literature due to lack of enantiospecific bioanalytical methods. No single dose pharmacokinetic study of IX exists in the literature for any species. This study elucidates the enantiospecific pharmacokinetics of IX in rats and monitors the appearance of 8PN following intravenous and oral administration of ±IX.
Methods and results
After intravenous (10 mg/kg) or oral (100 mg/kg) administration of ±IX to rats, serum, and urine were collected for 120 h and analyzed for IX and 8PN. Both were found as aglycones and glucuronide conjugates and displayed multiple peaking in serum suggestive of enterohepatic recycling. IX is primarily excreted through nonrenal routes. S‐8PN was found excreted in the urine in greater amounts than R‐8PN. Bioavailability was determined to be ∼4–5% for IX.
Conclusion
Further enantiospecific pharmacokinetics of IX, subsequent 8PN and other metabolites are warranted along with continued enantiospecific bioactivity studies, especially in relation to gut microbial metabolism of IX and subsequent formation of 8PN.</description><subject>Administration, Intravenous</subject><subject>Administration, Oral</subject><subject>Animals</subject><subject>Biological Availability</subject><subject>Chiral</subject><subject>Circular Dichroism</subject><subject>Dietary Supplements</subject><subject>Flavanones - blood</subject><subject>Flavanones - pharmacokinetics</subject><subject>Flavanones - urine</subject><subject>Flavonoids</subject><subject>Glucuronides - blood</subject><subject>Humulus - chemistry</subject><subject>Isoxanthohumol</subject><subject>LC-MS</subject><subject>Male</subject><subject>Pharmacokinetics</subject><subject>Plant Extracts - blood</subject><subject>Plant Extracts - pharmacokinetics</subject><subject>Plant Extracts - urine</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Xanthones - blood</subject><subject>Xanthones - pharmacokinetics</subject><subject>Xanthones - urine</subject><issn>1613-4125</issn><issn>1613-4133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtv1DAQhyMEog-4ckQ-csky41fSI7vqA6kPFYE4Wq4zYU0TO9he0f3vyWrbvSKNNHP4fj9pvqr6gLBAAP55DH1acEAFgNi-qo5Ro6glCvH6cHN1VJ3k_BtAIJfibXXENTRnrcbjyp0HG4qPeSLne-_YtLZptC4--kDFu8xiz3yOTzO1juvNGAdmQ8d8yWykYh_i4Auxtp4She0QbPLhFwUf2DxlTSzZ8q5609sh0_vnfVr9uDj_vrqqr-8uv66-XNdOoWzrllQDUqFSTnUd72VPhFaBbNvOaSICPb-iwMkOkGviyKEDK89c23DXNeK0-rTvnVL8s6FczOizo2GwgeImG2xQaQ1K4Ywu9qhLMedEvZmSH23aGgSzE2t2Ys1B7Bz4-Ny9eRipO-AvJmdA7oG_fqDtf-rMze3FNy75rrfex3wu9HSI2fRodCMaZX7eXhqxbHB5v1oaJf4B9GWUCQ</recordid><startdate>201509</startdate><enddate>201509</enddate><creator>Martinez, Stephanie E.</creator><creator>Davies, Neal M.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>201509</creationdate><title>Enantiospecific pharmacokinetics of isoxanthohumol and its metabolite 8-prenylnaringenin in the rat</title><author>Martinez, Stephanie E. ; Davies, Neal M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5148-8e57045155c5dd2f4fee1a50488dc6eee0612550c4d0126e2120d0a49c872cd73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Administration, Intravenous</topic><topic>Administration, Oral</topic><topic>Animals</topic><topic>Biological Availability</topic><topic>Chiral</topic><topic>Circular Dichroism</topic><topic>Dietary Supplements</topic><topic>Flavanones - blood</topic><topic>Flavanones - pharmacokinetics</topic><topic>Flavanones - urine</topic><topic>Flavonoids</topic><topic>Glucuronides - blood</topic><topic>Humulus - chemistry</topic><topic>Isoxanthohumol</topic><topic>LC-MS</topic><topic>Male</topic><topic>Pharmacokinetics</topic><topic>Plant Extracts - blood</topic><topic>Plant Extracts - pharmacokinetics</topic><topic>Plant Extracts - urine</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Xanthones - blood</topic><topic>Xanthones - pharmacokinetics</topic><topic>Xanthones - urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Martinez, Stephanie E.</creatorcontrib><creatorcontrib>Davies, Neal M.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular nutrition & food research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martinez, Stephanie E.</au><au>Davies, Neal M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enantiospecific pharmacokinetics of isoxanthohumol and its metabolite 8-prenylnaringenin in the rat</atitle><jtitle>Molecular nutrition & food research</jtitle><addtitle>Mol. Nutr. Food Res</addtitle><date>2015-09</date><risdate>2015</risdate><volume>59</volume><issue>9</issue><spage>1674</spage><epage>1689</epage><pages>1674-1689</pages><issn>1613-4125</issn><eissn>1613-4133</eissn><abstract>Scope
Isoxanthohumol (IX) is a bioactive dietary prenylflavanone found in hops (Humulus lupulus L.), beer and nutraceuticals. IX is formed in vivo by xanthohumol and is a prodrug of 8‐prenylnaringenin (8PN). IX and 8PN chirality has largely been ignored in the literature due to lack of enantiospecific bioanalytical methods. No single dose pharmacokinetic study of IX exists in the literature for any species. This study elucidates the enantiospecific pharmacokinetics of IX in rats and monitors the appearance of 8PN following intravenous and oral administration of ±IX.
Methods and results
After intravenous (10 mg/kg) or oral (100 mg/kg) administration of ±IX to rats, serum, and urine were collected for 120 h and analyzed for IX and 8PN. Both were found as aglycones and glucuronide conjugates and displayed multiple peaking in serum suggestive of enterohepatic recycling. IX is primarily excreted through nonrenal routes. S‐8PN was found excreted in the urine in greater amounts than R‐8PN. Bioavailability was determined to be ∼4–5% for IX.
Conclusion
Further enantiospecific pharmacokinetics of IX, subsequent 8PN and other metabolites are warranted along with continued enantiospecific bioactivity studies, especially in relation to gut microbial metabolism of IX and subsequent formation of 8PN.</abstract><cop>Germany</cop><pub>Blackwell Publishing Ltd</pub><pmid>26079861</pmid><doi>10.1002/mnfr.201500118</doi><tpages>16</tpages></addata></record> |
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| ispartof | Molecular nutrition & food research, 2015-09, Vol.59 (9), p.1674-1689 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Administration, Intravenous Administration, Oral Animals Biological Availability Chiral Circular Dichroism Dietary Supplements Flavanones - blood Flavanones - pharmacokinetics Flavanones - urine Flavonoids Glucuronides - blood Humulus - chemistry Isoxanthohumol LC-MS Male Pharmacokinetics Plant Extracts - blood Plant Extracts - pharmacokinetics Plant Extracts - urine Rats Rats, Sprague-Dawley Xanthones - blood Xanthones - pharmacokinetics Xanthones - urine |
| title | Enantiospecific pharmacokinetics of isoxanthohumol and its metabolite 8-prenylnaringenin in the rat |
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