Effects of Curcuma spp. on P-glycoprotein function.
The effects of Curcuma longa (khamin chan) and Curcuma sp. "khamin-oi" (khamin-oi), as well as isolated major curcuminoids on intestinal P-gp functions were evaluated in vitro. The accumulation of R123 in Caco-2 cells was increased and the R123 efflux ratios were significantly decreased by both Curcuma longa and Curcuma sp. "khamin-oi" extracts, indicating their roles on efflux transporters. The a-b transport of daunorubicin was increased by curcumin, demethoxycurcumin and bisdemethoxycurcumin while the b-a transport was significantly decreased by curcumin and demethoxycurcumin. However, calcein-AM uptake into the human P-gp overexpression cell line, LLC-GA5-COL300, was increased by curcumin and demethoxycurcumin in a concentration-dependent manner but not affected by bisdemethoxycurcumin. These results show that curcumin and demethoxycurcumin could inhibit P-gp but bisdemethoxycurcumin may modulate the function of other efflux transporters such as MRP. Taken together, the information may indicate the impact of Curcuma longa and Curcuma sp. "khamin-oi" on pharmacokinetics of orally administered drugs that are P-gp substrates.
Ampasavate
Chadarat
C
Department of Pharmaceutical Sciences , Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
Sotanaphun
Uthai
U
Phattanawasin
Panadda
P
Piyapolrungroj
Nusara
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D018938:Caco-2 Cells; D002460:Cell Line; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003630:Daunorubicin / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005452:Fluoresceins / Q000493:pharmacokinetics; D041743:Herb-Drug Interactions; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D012235:Rhodamines / Q000493:pharmacokinetics; D013552:Swine
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005452:Fluoresceins; D010936:Plant Extracts; D012235:Rhodamines; C085925:calcein AM; D003474:Curcumin; D003630:Daunorubicin