The alkaloid rutaecarpine exhibits antithrombotic and vasorelaxant effects. To characterize mouse cytochrome P450 (P450, CYP)-catalyzed rutaecarpine hydroxylations, the induction, inhibition, and kinetic properties of rutaecarpine hydroxylations were determined using liver microsomes of C57BL/6J mice. In untreated mice, rutaecarpine 10-, ll-, 12, and 3-hydroxylation had Km and Vmax values ranging, respectively, between 11.6-16.7 μM and 62-97 pmol/min/mg protein. The formation rates of the four hydroxylated metabolites were inhibited by α-naphthoflavone and orphenadrine, but not by either sulfaphenazole or ketoconazole. 3-Methylcholanthrene-treatment increased rutaecarpine ll-, 12-, and 3-hydroxylation activities. Phenobarbital-treatment increased rutaecarpine 10-, ll-, 12-, and 3-hydroxylation activities. Dexamethasone had no effect on these hydroxylation reactions in mice. These results indicated that CYP1A and CYP2B, but not CYP3A, play major roles in rutaecarpine hydroxylations in mice.
Jan, W.-C.; Don, M.-J.; Ho, L.-K.; Chen, C.-F.; and Ueng, Y.-F.
"Characterization of mouse cytochrome P450-catalyzed Oxidative metabolism of rutaecarpine, an alkaloid in the herbal medicine evodia rutaecarpa,"
Journal of Food and Drug Analysis: Vol. 14
, Article 10.
Available at: https://doi.org/10.38212/2224-6614.2489