Dataset Information

Inhibition of melatonin metabolism in humans induced by chemical components from herbs and effective prediction of this risk using a computational model.

ABSTRACT:

Background and purpose

Herbs which are widely used as food and medicine, are involved in many physiopathological processes. Melatonin is a human hormone, synthesized and secreted by the pineal gland, with a range of biological functions. Here, we have evaluated the potential influences of components extracted from common herbs on melatonin metabolism in humans.

Experimental approach

An in vivo pharmacokinetic study involving 12 healthy subjects, in vitro incubations with human liver microsomes (HLMs) and recombinant human cytochrome P (CYP) isoenzymes and an in silico quantitative structure-activity relationship (QSAR) model analysis using comparative molecular field analysis and comparative molecular similarity indices analysis methods were employed to explore these interactions.

Key results

After systematic screening of 66 common herbs, Angelica dahurica exhibited the most potent inhibition of melatonin metabolism in vitro. The in vivo pharmacokinetic study indicated inhibition of melatonin metabolism, with approximately 12- and 4-fold increases in the AUC and C_max of melatonin in human subjects. Coumarins from A. dahurica, including imperatorin, isoimperatorin, phellopterin, 5-methoxypsoralen and 8-methoxypsoralen, markedly inhibited melatonin metabolism with K_i values of 14.5 nM, 38.8 nM, 6.34 nM, 5.34 nM and 18 nM respectively, through inhibition of CYP 1A2, 1A1 and 1B1 in HLMs. A QSAR model was established and satisfactorily predicted the potential risk of coumarins for inhibition of melatonin metabolism in vivo.

Conclusion and implications

Coumarins from A. dahurica inhibited melatonin metabolism in vivo and in vitro. Our findings provide vital guidance for the clinical use of melatonin.

SUBMITTER: Wang C

PROVIDER: S-EPMC5071560 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Inhibition of melatonin metabolism in humans induced by chemical components from herbs and effective prediction of this risk using a computational model.

Wang Chao C Huo Xiaokui X Tian Xiangge X Xu Min M Dong Peipei P Luan Zhilin Z Wang Xiaobo X Zhang Baojing B Zhang Bo B Huang Shanshan S Deng Sa S Ma Xiaochi X

British journal of pharmacology 20161010 22

<h4>Background and purpose</h4>Herbs which are widely used as food and medicine, are involved in many physiopathological processes. Melatonin is a human hormone, synthesized and secreted by the pineal gland, with a range of biological functions. Here, we have evaluated the potential influences of components extracted from common herbs on melatonin metabolism in humans.<h4>Experimental approach</h4>An in vivo pharmacokinetic study involving 12 healthy subjects, in vitro incubations with human liv ...[more]

PMID: 27588415

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Dataset Information

Inhibition of melatonin metabolism in humans induced by chemical components from herbs and effective prediction of this risk using a computational model.

Background and purpose

Experimental approach

Key results

Conclusion and implications

Publications

Inhibition of melatonin metabolism in humans induced by chemical components from herbs and effective prediction of this risk using a computational model.

Similar Datasets

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