title: Metabolism of Nω -methylserotonin, a serotonergic constituent of black cohosh (Cimicifuga racemosa, L. (Nutt.)), by human liver microsomes.
abstract: The roots/rhizomes of black cohosh (Cimicifuga racemosa L. (Nutt.) (syn. Actaea racemosa L.) are a popular dietary supplements among women for management of menopausal symptoms. Although not estrogenic, Nω -methylserotonin has been identified in black cohosh as a potent agonist of serotonin 5-HT1A and 5-HT7 receptors. In the present study, in vitro metabolism of Nω -methylserotonin was investigated to gain insights into aspects of the bioavailability of this compound. The major metabolic pathway was determined to be conversion into 5-hydroxyindole acetaldehyde catalyzed by the monoamine oxidase A (MAO-A). 5-Hydroxyindole acetaldehyde could be further oxidized to form 5-hydroxyindole acetic acid by the action of microsomal aldehyde dehydrogenase or reduced to 5-hydroxy tryptophol by the action of aldehyde reductase. The cytochrome P450 enzymes had only a minor role in the metabolism of Nω -methylserotonin and then only when MAO-A was inhibited. In many aspects, the metabolism of Nω -methylserotonin was similar to the metabolism of serotonin, suggesting that this compound is unlikely to elicit CNS effects due to rapid metabolism by the widely distributed MAO-A.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, UIC/NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St, Chicago, IL, 60612-7231, USA.
authors.forename: Dejan
authors.initials: D
authors.lastname: Nikolić
authors.forename: Jinghu
authors.initials: J
authors.lastname: Li
authors.forename: Richard B
authors.initials: RB
authors.lastname: van Breemen
mesh_terms: D002851:Chromatography, High Pressure Liquid; D031885:Cimicifuga / Q000737:chemistry*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D012701:Serotonin / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism
chemical_list: D010936:Plant Extracts; C008494:N-methylserotonin; D012701:Serotonin; D008995:Monoamine Oxidase
keywords: N-methylserotonin; black cohosh; mass spectrometry; metabolism