Effects of Schisandra lignans on P-glycoprotein-mediated drug efflux in human intestinal Caco-2.
Schisandra fruits (Schisandraceae) are often used in traditional medicine and can be taken concomitantly with conventional medicine. In this study, the effects of dibenzocyclooctadiene lignans from Schizandra chinensis on P-gp-mediated efflux were examined to investigate a possible interaction with P-gp substrates. The cellular accumulation of rhodamine-123 in Caco-2 cells was measured with 12 Schisandra lignans. Most compounds resulted in slight or moderate increases of rhodamin-123 cellular uptake, indicating their P-gp inhibitory activity. Among them, deoxyschizandrin exhibited the most potent effect on the accumulation of rhodamine-123. Subsequently, bidirectional transports of digoxin and rhodamine-123 in Caco-2 cells were determined with deoxyschizandrin, the most active compound for the rhodamine-123 assay. In the bidirectional transport study, apical-to-basal (A-to-B) transports of digoxin and rhodamine-123 were increased, whereas basal-to-apical (B-to-A) transports were decreased by deoxyschizandrin in concentration- and time-dependent manners. At 50 microM of deoxyschizandrin, the transport ratios (B-A/A-B) for digoxin and rhodamine-123 were 2.2 and 2.1 compared with the control ratios of 15.2 and 12.2, respectively. These results demonstrated that deoxyschizandrin effectively inhibited the P-gp-mediated efflux in Caco-2 cells, suggesting they could potentially increase the absorption of drugs that can act as a P-gp substrate.
Yoo
Hye Hyun
HH
Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, Seoul, Korea.
Lee
Mijin
M
Lee
Min Woo
MW
Lim
Sun Young
SY
Shin
Jongheon
J
Kim
Dong-Hyun
DH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D034242:Cyclooctanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004077:Digoxin / Q000378:metabolism; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D020112:Rhodamine 123 / Q000378:metabolism; D032141:Schisandra / Q000737:chemistry*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D034242:Cyclooctanes; D017705:Lignans; D011083:Polycyclic Compounds; C510994:dibenzocyclooctadiene lignan; D020112:Rhodamine 123; D004077:Digoxin; C034734:schizandrin A