RRC ID 42366
Author Yoshida N, Takagi A, Kitazawa H, Kawakami J, Adachi I.
Title Inhibition of P-glycoprotein-mediated transport by extracts of and monoterpenoids contained in Zanthoxyli fructus.
Journal Toxicol Appl Pharmacol
Abstract Citrus (rutaceous) herbs are often used in traditional medicine and Japanese cuisine and can be taken concomitantly with conventional medicine. In this study, the effect of various citrus-herb extracts on P-glycoprotein (P-gp)-mediated transport was examined in vitro to investigate a possible interaction with P-gp substrates. Component monoterpenoids of the essential oil in Zanthoxyli fructus was screened to find novel P-gp inhibitors. LLC-GA5-COL150 cells transfected with human MDR1 cDNA encoding P-gp were used. Cellular accumulation of [3H]digoxin was measured in the presence or absence of P-gp inhibitors or test samples. Aurantii fructus, Evodiae fructus, Aurantii fructus immaturus, Aurantii nobilis pericarpium, Phellodendri cortex, and Zanthoxyli fructus were extracted with hot water (decocted) and then fractionated with ethyl acetate. The cell to medium ratio of [3H]digoxin accumulation increased significantly in the presence of the decoction of Evodiae fructus, Aurantii nobilis pericarpium, and Zanthoxyli fructus, and the ethyl acetate fraction of all citrus herbs used. The ethyl acetate fraction of Zanthoxyli fructus exhibited the strongest inhibition of P-gp among tested samples with an IC50 value of 166 microg/mL. Then its component monoterpenoids, geraniol, geranyl acetate, (R)-(+)-limonene, (R)-(+)-linalool, citronellal, (R)-(+)-citronellal, DL-citronellol, (S)-(-)-beta-citronellol, and cineole, were screened. (R)-(+)-citronellal and (S)-(-)-beta-citronellol inhibited P-gp with IC50 values of 167 microM and 504 microM, respectively. These findings suggest that Zanthoxyli fructus may interact with P-gp substrates and that some monoterpenoids with the relatively lower molecular weight of about 150 such as (R)-(+)-citronellal can be potent inhibitors of P-gp.
Volume 209(2)
Pages 167-73
Published 2005-12-1
DOI 10.1016/j.taap.2005.04.001
PII S0041-008X(05)00164-X
PMID 15890377
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors* ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism* Acyclic Monoterpenes Aldehydes / pharmacology Animals Biological Transport / drug effects Cyclosporins / pharmacology Digoxin / antagonists & inhibitors Digoxin / pharmacokinetics Drug Interactions Humans Inhibitory Concentration 50 LLC-PK1 Cells Monoterpenes / pharmacology* Plant Extracts / pharmacology* Swine Transfection Verapamil / pharmacology Zanthoxylum / chemistry*
IF 3.585
Times Cited 35
Human and Animal Cells