Abstract：
:Curcumin, a specific secondary metabolite of Curcuma species, has potentials for a variety of beneficial health effects. It is nowadays used as a dietary supplement. Everolimus (EVL) is an immunosuppressant indicated for allograft rejection and cancer therapy, but with narrow therapeutic window. EVL is a substrate of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4). This study investigated the effect of coadministration of curcumin on the pharmacokinetics of EVL in rats and the underlying mechanisms. EVL (0.5 mg/kg) was orally administered without and with 50 and 100 mg/kg of curcumin, respectively, in rats. Blood samples were collected at specific time points and EVL concentrations in blood were determined by QMS immunoassay. The underlying mechanisms were evaluated using cell model and recombinant CYP 3A4 isozyme. The results indicated that 50 and 100 mg/kg of curcumin significantly decreased the AUC0-540 of EVL by 70.6% and 71.5%, respectively, and both dosages reduced the Cmax of EVL by 76.7%. Mechanism studies revealed that CYP3A4 was markedly activated by curcumin metabolites, which apparently overrode the inhibition effects of curcumin on P-gp. In conclusion, oral intake of curcumin significantly decreased the bioavailability of EVL, a probe substrate of P-gp/CYP 3A4, mainly through marked activation on CYP 3A4.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Hsieh YW,Huang CY,Yang SY,Peng YH,Yu CP,Chao PD,Hou YCdoi
10.1038/srep06587subject
Has Abstractpub_date
2014-10-10 00:00:00pages
6587issn
2045-2322pii
srep06587journal_volume
4pub_type
杂志文章abstract：:1-Aminocyclopropane-1-carboxylic acid (ACC) is a precursor molecule of ethylene whose concentration is elevated in the plant subjected to biotic and abiotic stress. Several soil microorganisms are reported to produce ACC deaminase (ACCd) which degrades ACC thereby reducing stress ethylene in host plants. This study is...
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pub_type： 杂志文章,meta分析,评审
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更新日期：2013-01-01 00:00:00
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更新日期：2016-09-06 00:00:00
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pub_type： 杂志文章
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更新日期：2014-07-28 00:00:00
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pub_type： 杂志文章
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pub_type： 已发布勘误
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journal_title：Scientific reports
pub_type： 杂志文章
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journal_title：Scientific reports
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更新日期：2016-01-25 00:00:00
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