Abstract:
:Acanthopanax senticosus HARMS (AS) is used as a Chinese herbal medicine and as a health supplement in Japan. However, little is known about the interaction between AS and other drugs. In this study, we investigated the effect of AS extract on intestinal drug transporter (P-glycoprotein, or P-gp) and peptide transporter activities in Caco-2 cells. Caco-2 cells were cultured on a culture dish and a permeable membrane for 1-3 weeks. The apical-to-basolateral (A-to-B) transport of digoxin, a P-gp substrate, was significantly increased by the addition of AS extract in a concentration-dependent manner. In contrast, the A-to-B transport of cephalexin, a peptide transporter substrate, was significantly decreased by the addition of AS extract in the same manner. The effects of AS extract addition on the kinetics of the uptake of rhodamine 123, a P-gp substrate, and Gly-Sar, a peptide transporter substrate, were investigated. V (max) for rhodamine 123 uptake was significantly increased by AS extract addition compared with the control, whereas that for Gly-Sar uptake was significantly decreased. On the other hand, K (m) and K (d) for rhodamine 123 and Gly-Sar uptake were not affected. We conducted further investigations to clarify the effect of AS extract addition on P-gp activity. When AS extract was added to the apical side, B-to-A transport of rhodamine 123 was significantly decreased compared with the control. Furthermore, the amount of intracellular rhodamine 123 was increased by AS extract addition compared with the control. These results suggest that P-gp and peptide transporter activities are suppressed by AS extract addition in a non-competitive manner.
journal_name
J Nat Medjournal_title
Journal of natural medicinesauthors
Takahashi T,Kaku T,Sato T,Watanabe K,Sato Jdoi
10.1007/s11418-009-0371-3subject
Has Abstractpub_date
2010-01-01 00:00:00pages
55-62issue
1eissn
1340-3443issn
1861-0293journal_volume
64pub_type
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