title: Effects of Acanthopanax senticosus HARMS extract on drug transport in human intestinal cell line Caco-2.
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.
authors.affiliation: Yakuhan Pharmaceutical Co., Ltd., 27 Kitanosato, Kitahiroshima, Hokkaido, Japan. kenkyu@yakuhan.co.jp
authors.forename: Tsunehisa
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kaku
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Juichi
authors.initials: J
authors.lastname: Sato
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002506:Cephalexin / Q000493:pharmacokinetics; D004077:Digoxin / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D028001:Eleutherococcus / Q000737:chemistry*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D020112:Rhodamine 123 / Q000493:pharmacokinetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004365:Drugs, Chinese Herbal; D026901:Membrane Transport Proteins; D010936:Plant Extracts; D020112:Rhodamine 123; D004077:Digoxin; C043912:peptide permease; D002506:Cephalexin