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Alkaloids and saponins as cytochrome P450 inhibitors from blue cohosh (Caulophyllum thalictroides) in an in vitro assay.

Abstract：

:Blue cohosh, Caulophyllum thalictroides (L.) Michx. is a popular herb, roots and rhizomes of which have been extensively used for women's health. Alkaloids and saponins are considered to be responsible for its pharmacological effects. In this investigation the methanolic extract of the roots of blue cohosh, the alkaloidal fraction and isolated constituents were evaluated for their inhibition of major drug metabolizing cytochrome P450 (CYP450) enzymes. The methanolic extract did not show any effect but the alkaloidal fraction showed a strong inhibition of CYP 2C19, 3A4, 2D6, and 1A2 (>80% inhibition at 100 microg/mL) with IC50 values in the range of 2-20 microg/mL. Among the isolated alkaloids, a piperidine-type alkaloid (caulophyllumine B) and three lysine-derived alkaloids (O-acetlybaptifolin, anagyrine, and lupanine) inhibited these enzymes to various extents (IC50:2.5-50 microM). N-Methylcytisine weakly inhibited CYP3A4 only (32% inhibition at 100 microM). An equimolar mixture of alkaloids exhibited a more pronounced inhibitory effect on all four enzymes as compared to the isolated alkaloids. Among the saponins, caulosides C and D inhibited CYP3A4 at the highest test concentration of 100 microM (43% and 35% inhibition, respectively). Other enzymes were not affected. This in vitro study indicates that dietary supplements containing blue cohosh may pose a risk of drug-drug interactions if taken with other drugs or herbs, metabolism of which involves CYP450 enzymes.

journal_name

Planta Med

journal_title

Planta medica

authors

Madgula VL,Ali Z,Smillie T,Khan IA,Walker LA,Khan SI

doi

10.1055/s-0028-1112207

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

329-32

issue

4

eissn

0032-0943

issn

1439-0221

journal_volume

75

pub_type

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