Abstract: Antrodia cinnamomea is a precious medicinal mushroom. It exhibits promising therapeutic effects on cancer, intoxication, hypertension, hepatitis, and inflammation. Its major bioactive constituents are ergostane and lanostane triterpenoids. In this study, we used intestinal Caco-2 cell monolayer model to reveal the intestinal absorption property of 14 representative triterpenoids from A. cinnamomea. The bidirectional transport through the monolayer at different time points was monitored by a fully validated LC/MS/MS method. In the case of pure compounds, ergostanes 5(25R-antcin H), 6(25S-antcin H) and 10(25R-antcin B) could readily pass through the Caco-2 cell layer, whereas lanostanes 13(dehydroeburicoic acid) and 14(eburicoic acid) could hardly pass through. When the cells were treated with A. cinnamomea extract, antcins A, B, C, H and K(1-6 and 9-11) were absorbed via passive transcellular diffusion, and showed high P_AB and P_BA values(>2.5×10^-5 cm/s). Meanwhile, the lanostanes dehydrosulphurenic acid(8), 15α-acetyldehydrosulphurenic acid(12), 13 and 14 exhibited poor permeability. Transport features of these compounds were consistent with their pharmacokinetic behaviors in rats. This study could also be helpful in predicting the intestinal absorption of A. cinnamomea in human.

Key words: Antrodia cinnamomea, Ergostane, Lanostane, Triterpenoids, Caco-2

摘要： Antrodia cinnamomea is a precious medicinal mushroom. It exhibits promising therapeutic effects on cancer, intoxication, hypertension, hepatitis, and inflammation. Its major bioactive constituents are ergostane and lanostane triterpenoids. In this study, we used intestinal Caco-2 cell monolayer model to reveal the intestinal absorption property of 14 representative triterpenoids from A. cinnamomea. The bidirectional transport through the monolayer at different time points was monitored by a fully validated LC/MS/MS method. In the case of pure compounds, ergostanes 5(25R-antcin H), 6(25S-antcin H) and 10(25R-antcin B) could readily pass through the Caco-2 cell layer, whereas lanostanes 13(dehydroeburicoic acid) and 14(eburicoic acid) could hardly pass through. When the cells were treated with A. cinnamomea extract, antcins A, B, C, H and K(1-6 and 9-11) were absorbed via passive transcellular diffusion, and showed high P_AB and P_BA values(>2.5×10^-5 cm/s). Meanwhile, the lanostanes dehydrosulphurenic acid(8), 15α-acetyldehydrosulphurenic acid(12), 13 and 14 exhibited poor permeability. Transport features of these compounds were consistent with their pharmacokinetic behaviors in rats. This study could also be helpful in predicting the intestinal absorption of A. cinnamomea in human.

关键词: Antrodia cinnamomea, Ergostane, Lanostane, Triterpenoids, Caco-2