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In Vitro Serotonergic Activity of Black Cohosh and Identification of Nω-Methylserotonin as a Potential Active Constituent

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Department of Medicinal Chemistry and Pharmacognosy and UIC/NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, 833 South Wood Street, M/C 781, University of Illinois at Chicago, Chicago, Illinois 60612-7231
* Corresponding author [telephone (312) 996-5280; fax (312) 996-7107; e-mail [email protected]].
Cite this: J. Agric. Food Chem. 2008, 56, 24, 11718–11726
Publication Date (Web):December 2, 2008
https://doi.org/10.1021/jf803298z
Copyright © 2008 American Chemical Society
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Abstract

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Cimicifuga racemosa (L.) Nutt. (syn. Actaea racemosa L., black cohosh) is used to relieve menopausal hot flashes, although clinical studies have provided conflicting data, and the active constituent(s) and mechanism(s) of action remain unknown. Because serotonergic receptors and transporters are involved with thermoregulation, black cohosh and its phytoconstituents were evaluated for serotonergic activity using 5-HT7 receptor binding, cAMP induction, and serotonin selective re-uptake inhibitor (SSRI) assays. Crude extracts displayed 5-HT7 receptor binding activity and induced cAMP production. Fractionation of the methanol extract led to isolation of phenolic acids and identification of Nω-methylserotonin by LC-MS/MS. Cimicifuga triterpenoids and phenolic acids bound weakly to the 5-HT7 receptor with no cAMP or SSRI activity. In contrast, Nω-methylserotonin showed 5-HT7 receptor binding (IC50 = 23 pM), induced cAMP (EC50 = 22 nM), and blocked serotonin re-uptake (IC50 = 490 nM). These data suggest Nω-methylserotonin may be responsible for the serotonergic activity of black cohosh.

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