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Inhibition of P-glycoprotein-mediated transport by extracts of and monoterpenoids contained in Zanthoxyli fructus
Inhibition of P-glycoprotein-mediated transport by extracts of and monoterpenoids contained in Zanthoxyli fructus
- Source :
- Toxicology and applied pharmacology. 209(2)
- Publication Year :
- 2005
-
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 [ 3 H]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 [ 3 H]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 IC 50 value of 166 μg/mL. Then its component monoterpenoids, geraniol, geranyl acetate, ( R )-(+)-limonene, ( R )-(+)-linalool, citronellal, ( R )-(+)-citronellal, dl -citronellol, ( S )-(−)-β-citronellol, and cineole, were screened. ( R )-(+)-citronellal and ( S )-(−)-β-citronellol inhibited P-gp with IC 50 values of 167 μM and 504 μM, 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.
- Subjects :
- Zanthoxylum
Digoxin
Swine
Acyclic Monoterpenes
Ethyl acetate
Decoction
Geranyl acetate
Cyclosporins
Toxicology
Transfection
law.invention
chemistry.chemical_compound
Inhibitory Concentration 50
law
Animals
Humans
Drug Interactions
ATP Binding Cassette Transporter, Subfamily B, Member 1
Essential oil
Pharmacology
chemistry.chemical_classification
Citronellol
Aldehydes
Chromatography
Chemistry
Plant Extracts
Glycoside
Biological Transport
Verapamil
Citronellal
Monoterpenes
LLC-PK1 Cells
Geraniol
Subjects
Details
- ISSN :
- 0041008X
- Volume :
- 209
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Toxicology and applied pharmacology
- Accession number :
- edsair.doi.dedup.....d4ccd369d4fd965a7156c9cb49c9a164