skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Inhibition of P-glycoprotein-mediated transport by extracts of and monoterpenoids contained in Zanthoxyli Fructus

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 [{sup 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 [{sup 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{sub 5} value of 166 {mu}g/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 withmore » IC{sub 5} values of 167 {mu}M and 504 {mu}M, 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.« less

Authors:
 [1];  [1];  [1];  [1];  [1]
  1. Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194 (Japan)
Publication Date:
OSTI Identifier:
20783380
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 209; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2005.04.001; PII: S0041-008X(05)00164-X; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETATES; ALCOHOLS; CITRUS; DIGOXIN; ESSENTIAL OILS; GLYCOPROTEINS; HERBS; IN VITRO; MOLECULAR WEIGHT; TERPENES; TRITIUM

Citation Formats

Yoshida, Naoko, Takagi, Akiyoshi, Kitazawa, Hidenori, Kawakami, Junichi, and Adachi, Isao. Inhibition of P-glycoprotein-mediated transport by extracts of and monoterpenoids contained in Zanthoxyli Fructus. United States: N. p., 2005. Web. doi:10.1016/j.taap.2005.04.001.
Yoshida, Naoko, Takagi, Akiyoshi, Kitazawa, Hidenori, Kawakami, Junichi, & Adachi, Isao. Inhibition of P-glycoprotein-mediated transport by extracts of and monoterpenoids contained in Zanthoxyli Fructus. United States. https://doi.org/10.1016/j.taap.2005.04.001
Yoshida, Naoko, Takagi, Akiyoshi, Kitazawa, Hidenori, Kawakami, Junichi, and Adachi, Isao. 2005. "Inhibition of P-glycoprotein-mediated transport by extracts of and monoterpenoids contained in Zanthoxyli Fructus". United States. https://doi.org/10.1016/j.taap.2005.04.001.
@article{osti_20783380,
title = {Inhibition of P-glycoprotein-mediated transport by extracts of and monoterpenoids contained in Zanthoxyli Fructus},
author = {Yoshida, Naoko and Takagi, Akiyoshi and Kitazawa, Hidenori and Kawakami, Junichi and Adachi, Isao},
abstractNote = {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 [{sup 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 [{sup 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{sub 5} value of 166 {mu}g/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 IC{sub 5} values of 167 {mu}M and 504 {mu}M, 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.},
doi = {10.1016/j.taap.2005.04.001},
url = {https://www.osti.gov/biblio/20783380}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 209,
place = {United States},
year = {Thu Dec 01 00:00:00 EST 2005},
month = {Thu Dec 01 00:00:00 EST 2005}
}