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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>An <jats:italic>in vivo<\/jats:italic> pharmacokinetic study involving 12 healthy subjects, <jats:italic>in vitro<\/jats:italic> incubations with human liver microsomes (HLMs) and recombinant human cytochrome P (CYP) isoenzymes and an <jats:italic>in silico<\/jats:italic> quantitative structure\u2013activity relationship (QSAR) model analysis using comparative molecular field analysis and comparative molecular similarity indices analysis methods were employed to explore these interactions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>After systematic screening of 66 common herbs, <jats:italic>Angelica dahurica<\/jats:italic> exhibited the most potent inhibition of melatonin metabolism <jats:italic>in vitro<\/jats:italic>. The <jats:italic>in vivo<\/jats:italic> pharmacokinetic study indicated inhibition of melatonin metabolism, with approximately 12\u2010 and 4\u2010fold increases in the AUC and C<jats:sub>max<\/jats:sub> of melatonin in human subjects. Coumarins from <jats:italic>A. dahurica<\/jats:italic>, including imperatorin, isoimperatorin, phellopterin, 5\u2010methoxypsoralen and 8\u2010methoxypsoralen, markedly inhibited melatonin metabolism with <jats:italic>K<\/jats:italic><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub> values of 14.5\u00a0nM, 38.8\u00a0nM, 6.34\u00a0nM, 5.34\u00a0nM and 18\u00a0nM 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 <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Coumarins from <jats:italic>A. dahurica<\/jats:italic> inhibited melatonin metabolism <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Our findings provide vital guidance for the clinical use of melatonin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13612","type":"journal-article","created":{"date-parts":[[2016,9,2]],"date-time":"2016-09-02T23:03:09Z","timestamp":1472857389000},"page":"3261-3275","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of melatonin metabolism in humans induced by chemical components from herbs and effective prediction of this risk using a computational model"],"prefix":"10.1111","volume":"173","author":[{"given":"Chao","family":"Wang","sequence":"first","affiliation":[{"name":"Academy of Integrative Medicine, College of Pharmacy, Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning Dalian Medical University  Dalian China"},{"name":"Department of Neurosurgery The Second Affiliated Hospital of Dalian Medical University  Dalian 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