Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged Rats
Aging is an inevitable biological process characterized by the loss of functional capacity and associated with changes in all phases of pharmacokinetic processes. Naringin, a dietary flavanone glycoside, has been proved to be beneficial for the treatment of multiple age-associated chronic diseases....
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doaj-8eecf0f80ccc4e09aa7ebe7e6068a2012020-11-24T21:52:51ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-01-011010.3389/fphar.2019.00034436859Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged RatsXuan ZengWeiwei SuYuying ZhengYudong HeYan HeHongyu RaoWei PengHongliang YaoAging is an inevitable biological process characterized by the loss of functional capacity and associated with changes in all phases of pharmacokinetic processes. Naringin, a dietary flavanone glycoside, has been proved to be beneficial for the treatment of multiple age-associated chronic diseases. To date, the pharmacokinetic processes of naringin in aged individuals are still unknown. Thus, a rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QQQ-MS/MS) method was established for the determination of naringin and its metabolite naringenin in rat plasma, urine, feces, and tissue homogenate. The pharmacokinetic parameters were calculated and a higher exposure of naringin and naringenin were observed in aged rats. Naringin and naringenin were mostly distributed in gastrointestinal tract, liver, kidney, lung, and trachea. Furthermore, a total of 39 flavonoid metabolites (mainly glucuronides and sulfates) and 46 microbial-derived phenolic catabolites were screened with ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). Naringenin, hippuric acid, and 3-(4’-hydroxyphenyl)propionic acid were predominated metabolites. This study systemically investigated the pharmacokinetics, tissue distribution, metabolism, and excretion of naringin in aged rats, revealing age- and gender-related changes in the in vivo behavior of naringin. These results would be helpful for the interpretation of pharmacokinetics and pharmacodynamics of naringin in aged population.https://www.frontiersin.org/article/10.3389/fphar.2019.00034/fullnaringinnaringeninADMEaged ratsLC-MS/MS |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xuan Zeng Weiwei Su Yuying Zheng Yudong He Yan He Hongyu Rao Wei Peng Hongliang Yao |
spellingShingle |
Xuan Zeng Weiwei Su Yuying Zheng Yudong He Yan He Hongyu Rao Wei Peng Hongliang Yao Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged Rats Frontiers in Pharmacology naringin naringenin ADME aged rats LC-MS/MS |
author_facet |
Xuan Zeng Weiwei Su Yuying Zheng Yudong He Yan He Hongyu Rao Wei Peng Hongliang Yao |
author_sort |
Xuan Zeng |
title |
Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged Rats |
title_short |
Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged Rats |
title_full |
Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged Rats |
title_fullStr |
Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged Rats |
title_full_unstemmed |
Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Naringin in Aged Rats |
title_sort |
pharmacokinetics, tissue distribution, metabolism, and excretion of naringin in aged rats |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2019-01-01 |
description |
Aging is an inevitable biological process characterized by the loss of functional capacity and associated with changes in all phases of pharmacokinetic processes. Naringin, a dietary flavanone glycoside, has been proved to be beneficial for the treatment of multiple age-associated chronic diseases. To date, the pharmacokinetic processes of naringin in aged individuals are still unknown. Thus, a rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QQQ-MS/MS) method was established for the determination of naringin and its metabolite naringenin in rat plasma, urine, feces, and tissue homogenate. The pharmacokinetic parameters were calculated and a higher exposure of naringin and naringenin were observed in aged rats. Naringin and naringenin were mostly distributed in gastrointestinal tract, liver, kidney, lung, and trachea. Furthermore, a total of 39 flavonoid metabolites (mainly glucuronides and sulfates) and 46 microbial-derived phenolic catabolites were screened with ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). Naringenin, hippuric acid, and 3-(4’-hydroxyphenyl)propionic acid were predominated metabolites. This study systemically investigated the pharmacokinetics, tissue distribution, metabolism, and excretion of naringin in aged rats, revealing age- and gender-related changes in the in vivo behavior of naringin. These results would be helpful for the interpretation of pharmacokinetics and pharmacodynamics of naringin in aged population. |
topic |
naringin naringenin ADME aged rats LC-MS/MS |
url |
https://www.frontiersin.org/article/10.3389/fphar.2019.00034/full |
work_keys_str_mv |
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