Document Detail

Inhibition of P-glycoprotein-mediated transport by terpenoids contained in herbal medicines and natural products.
MedLine Citation:
PMID:  16904803     Owner:  NLM     Status:  MEDLINE    
Terpenoids form a large and structurally diverse family of natural products and are ingredients of various herbal medicines. We have investigated possible interactions between herbal medicines and conventional medicines, and recently reported that monoterpenoids contained in Zanthoxyli Fructus can be potent inhibitors of P-glycoprotein (P-gp). In the present study, the influence of 70 kinds of terpenoids present in natural products on P-gp-mediated efflux transport was investigated. LLC-GA5-COL150 cells transfected with human MDR1 cDNA encoding P-gp were used to screen the terpenoids. Large increases in the intracellular accumulation of [(3)H]digoxin were observed in the presence of (R)-(+)-citronellal, (S)-(-)-beta-citronellol, alpha-terpinene, terpinolene, (-)-beta-pinene, abietic acid, ophiobolin A, cucurbitacin I, and glycyrrhetic acid. A study of the concentration-dependency revealed that the IC(50) of ophiobolin A, glycyrrhetic acid, (R)-(+)-citronellal, abietic acid, and cucurbitacin I was smaller than that of verapamil. The transcellular transport of [(3)H]digoxin across Caco-2 cell monolayers was then examined in the presence of (R)-(+)-citronellal, abietic acid, and glycyrrhetic acid. Significant increases in the apical-to-basolateral transport and decreases in the basolateral-to-apical transport and efflux ratio were demonstrated. These findings suggest that some natural products containing these terpenoids may inhibit P-gp-mediated transport and interact with P-gp substrates in the intestinal absorption process.
Naoko Yoshida; Mariya Koizumi; Isao Adachi; Junichi Kawakami
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-07-10
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  44     ISSN:  0278-6915     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-10-18     Completed Date:  2006-12-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2033-9     Citation Subset:  IM    
Department of Pharmacy, Toyama University Hospital, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
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MeSH Terms
Biological Transport / drug effects
Caco-2 Cells / drug effects,  metabolism,  pathology
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Antagonism
Drug Combinations
Intestinal Absorption / drug effects,  physiology
LLC-PK1 Cells / drug effects,  metabolism,  pathology
P-Glycoprotein / antagonists & inhibitors*,  metabolism
Plant Preparations / chemistry,  pharmacology*
Terpenes / analysis,  classification,  pharmacology*
Reg. No./Substance:
0/Drug Combinations; 0/P-Glycoprotein; 0/Plant Preparations; 0/Terpenes

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