Effects of diosmin, a flavonoid glycoside in citrus fruits, on P-glycoprotein-mediated drug efflux in human intestinal Caco-2 cells.
The effects of citrus flavonoids on P-glycoprotein (P-gp)-mediated drug efflux were examined in human intestinal Caco-2 cells. The cellular accumulation of rhodamine-123 was measured using 10 citrus flavonoids for preliminary screening. Among the flavonoids tested, diosmin significantly increased the accumulation of rhodamine-123 in Caco-2 cells. In the bidirectional transport of digoxin, diosmin increased the apical-to-basal (A-to-B) transport but decreased the basal-to-apical (B-to-A) transport in both concentration- and time-dependent manners. The digoxin transport ratio (B-A/A-B) was estimated to be 2.3 at a concentration of 50 microM of diosmin, which was significantly lower than the 15.2 found in the control. The apparent Ki values for P(app,A-B) and P(app,B-A) were 16.1 and 5.7 microM, respectively. These results demonstrated that diosmin effectively inhibited the P-gp-mediated efflux in Caco-2 cells. Diosmin is one of the main components in citrus fruits, and the intake of food supplements containing this compound may potentially increase the absorption of drugs able to act as P-gp substrates. The clinical relevance of this interaction should be further evaluated using in vivo experiments.
Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, PO Box 131, Chungryang, Seoul 130-650, Korea. behappy@kist.re.kr
Hye Hyun
HH
Yoo
Mijin
M
Lee
Hye Jin
HJ
Chung
Sang Kyu
SK
Lee
Dong-Hyun
DH
Kim
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002957:Citrus / Q000737:chemistry*; D004077:Digoxin / Q000378:metabolism; D004145:Diosmin / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects*; D020112:Rhodamine 123 / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D020112:Rhodamine 123; D004077:Digoxin; D004145:Diosmin