In vitro inhibitory effects of pulvinic acid derivatives isolated from Chinese edible mushrooms, Boletus calopus and Suillus bovinus, on cytochrome P450 activity.
Increasing attention has been focused on food-drug interactions. We have investigated the inhibitory effect of Chinese edible mushrooms, Boletus calopus and Suillus bovinus, on cytochrome P450 (CYP) 1A2, 2C9, 2D6, and 3A4, the main drug-metabolizing enzymes. Three pulvinic acid derivatives, atromentic acid (1), variegatic acid (2), and xerocomic acid (3), isolated from Boletus calopus and Suillus bovinus, revealed nonspecific inhibitory effects on all four CYPs. Using these compounds, the maximum IC50 values obtained with CYP3A4 in vitro were atromentic acid (1), 65.1+/-3.9 microM; variegatic acid (2), 2.2+/-0.1 microM; and xerocomic acid (3), 2.4+/-0.1 microM. Variegatic acid (2) and xerocomic acid (3) were effective inhibitors, comparable to cimetidine, dicoumarol, erythromycin, safrole, and uniconazole. Variegatic acid (2) and xerocomic acid (3) efficiently reduced ferryl myoglobin in CYPs. Reduction of ferryl heme to ferric heme is likely the mechanism of the nonspecific inhibitory effects of these compounds on CYPs.
Department of Nutritional Science, Faculty of Applied Bio-Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
Yu-Ting
YT
Huang
Jun-ichi
J
Onose
Naoki
N
Abe
Kunie
K
Yoshikawa
D000975:Antioxidants / Q000494:pharmacology; D001487:Basidiomycota / Q000737:chemistry*; D002264:Carboxylic Acids / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007783:Lactones / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D008786:Metmyoglobin / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects
D000975:Antioxidants; D002264:Carboxylic Acids; D002614:Chelating Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007783:Lactones; C028048:ferrylmyoglobin; D008786:Metmyoglobin; D003577:Cytochrome P-450 Enzyme System; C492654:pulvinic acid