Inhibition of Cytochrome P450 by Constituents from Blue Cohosh (Caulophyllum thalictroides)

Blue cohosh, Caulophyllum thalictriodes is a popular herb that is extensively used for women's health. Alkaloids and saponins are considered to be responsible for its pharmacological effects. In this study the effects of methanolic extract of the roots of blue cohosh, alkaloidal fraction and isolated constituents on major drug metabolizing cytochrome P450 (CYP450) enzymes were evaluated. 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 µg/mL) with IC50 values in the range of 2–20 µg/mL. Among the constituents, caulophyllumine B (a piperidine type alkaloid), O-acetlybaptifolin, anagyrine, and lupanine (lysine derived alkaloids) inhibited these enzymes to various extents (IC50 2.5–50 µM). N-methylcytisine weakly inhibited CYP3A4 (32% inhibition at 100 µM). A more pronounced inhibitory effect on all the four enzymes was observed by an equimolar mixture of alkaloids. Among the saponins, caulosides C and D inhibited CYP3A4 at the highest test concentration of 100 µM (43% and 35% inhibition, respectively). Other enzymes were not affected. This in vitro study indicates the possibility of drug-drug interactions. The dietary supplements containing blue cohosh may pose a risk if taken with other drugs or herbs, metabolism of which involves CYP450 enzymes. Acknowledgements: FDA grant no. FD-U-002071-07 and USDA, Agriculture Research Service Specific Cooperative Agreement no 58-6408-2-0009 are acknowledged for partial support of this work.