Effects of Curcuma extracts and curcuminoids on expression of P-glycoprotein and cytochrome P450 3A4 in the intestinal cell culture model LS180.
Curcuma longa L. is a widely used spice. Its main ingredients, the curcuminoids, are used in the treatment of inflammatory diseases and cancer. Bioavailability of curcuminoids is low, and huge amounts remain in the intestine. We therefore aimed to investigate their interaction potential with the ABC-transporter P-glycoprotein (P-gp, product of the MDR1/ABCB1 gene) and cytochrome P450 3A4 (CYP3A4) in an intestinal cell line (LS180). Intestinal P-gp and CYP3A4 play a major role in drug absorption, and consequently changes in their expression level could lead to interactions. The intestinal LS180 cell line was incubated with different Curcuma extracts, the single curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin), as well as a curcuminoid mixture. Changes in mRNA expression of MDR1 and the cytochrome CYP3A4 were measured by real-time RT-PCR. MDR1 mRNA expression was significantly but not relevantly downregulated by the curcuminoids, whereas the extracts had no significant effect on it. CYP3A4 mRNA expression did not alter significantly after treatment. Curcuma extracts, the single curcuminoids, and a curcuminoid mixture had no relevant effect on MDR1 and CYP3A4 mRNA expression in our intestinal cell system. Further studies are required to evaluate their effects in vivo.
Department of Clinical Pharmacology and Toxicology, University Hospital of Basel, Basel, Switzerland.
Angelika
A
Graber-Maier
Karin Berger
KB
Büter
Julia
J
Aeschlimann
Claudia
C
Bittel
Matthias
M
Kreuter
Juergen
J
Drewe
Heike
H
Gutmann
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D041743:Herb-Drug Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010936:Plant Extracts; D012333:RNA, Messenger; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D003474:Curcumin