| Fukinolic acid derivatives and triterpene glycosides from black cohosh inhibit CYP isozymes, but are not cytotoxic to Hep-G2 cells in vitro. | |
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MedLine Citation:
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PMID: 20406160 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Black cohosh (Actaea racemosa L. [syn. Cimifuga racemosa L.]) extracts (BCE) are marketed worldwide for the management of menopausal symptoms. However, recently more than 75 cases of hepatotoxicity associated with black cohosh ingestion have been reported. While these cases have not been fully substantiated for causality, the data suggest that herb-drug interactions may be involved rather than a direct hepatotoxic event. This work describes the in vitro inhibition of four CYP450 enzymes (1A2, 2D6, 2C9, 3A4) by black cohosh extracts and identifies the active inhibitory constituents. Ethanol extracts (75 and 80% ethanol) and a 40% isopropanol extract induced a concentration-dependent inhibition of all CYP450 isozyme activities, with median inhibitory concentrations (IC(50)) ranging from 21.9 microg/ml to 65.0 microg/ml. Isolation of the active chemical constituents, showed that the triterpene glycosides were weakly active (IC(50) 25-100 microM), while fukinolic acid and cimicifugic acids A and B strongly inhibited all CYP isozymes (IC(50) 1.8-12.6 microM). None of the extracts inhibited the growth of Hep-G2 cells in concentrations up to 50 microg/ml. These data suggest that BCEs are not directly hepatotoxic, but may have the potential to induce herb-drug interactions, which may in turn explain the rare cases of hepatotoxicity observed in women using multiple medications and dietary supplements, including black cohosh. |
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Authors:
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Yue Huang; Bei Jiang; Paiboon Nuntanakorn; Edward J Kennelly; Stacy Shord; Temitope O Lawal; G B Mahady |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Current drug safety Volume: 5 ISSN: 1574-8863 ISO Abbreviation: Curr Drug Saf Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-21 Completed Date: 2010-12-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101270895 Medline TA: Curr Drug Saf Country: United Arab Emirates |
Other Details:
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Languages: eng Pagination: 118-24 Citation Subset: IM |
Affiliation:
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Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St, Chicago, IL 60612, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Caffeic Acids
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chemistry,
isolation & purification,
pharmacology* Cimicifuga* Cytochrome P-450 Enzyme System / antagonists & inhibitors*, metabolism Cytotoxins / chemistry, isolation & purification, pharmacology* Female Glycosides / chemistry, isolation & purification, pharmacology* Hep G2 Cells Humans Isoenzymes / antagonists & inhibitors, metabolism Liver / drug effects, enzymology, pathology Menopause / drug effects, metabolism Phenylacetates / chemistry, isolation & purification, pharmacology* Plant Extracts / chemistry, isolation & purification, pharmacology Plant Roots Rhizome Triterpenes / chemistry, isolation & purification, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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AT02381-02/AT/NCCAM NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Caffeic Acids; 0/Cytotoxins; 0/Glycosides; 0/Isoenzymes; 0/Phenylacetates; 0/Plant Extracts; 0/Triterpenes; 50982-40-6/fukinolic acid; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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