Effects of praeruptorin A and praeruptorin C, a racemate isolated from Peucedanum praeruptorum, on MRP2 through the CAR pathway.
Praeruptorin A and praeruptorin C, racemic to each other, are main bioactive constituents of the species Peucedanum praeruptorum, traditionally used as a Chinese herbal medicine (also known as Bai-Hua Qian Hu). In the present study, the ability of praeruptorins A and C to activate the constitutive androstane receptor and induce human multidrug resistance-associated protein 2 expressions in HepG2 cells was investigated. The changes in mRNA level, protein expression, and transport activity of multidrug resistance-associated protein 2 were determined by quantitative real-time PCR, Western blot, and the CDF uptake assay, respectively. The effects of constitutive androstane receptor knockdown on multidrug resistance-associated protein 2 mRNA and protein expression were also measured by transient transfection of a specific constitutive androstane receptor siRNA. The results showed that praeruptorin A and praeruptorin C significantly induced the multidrug resistance-associated protein 2 mRNA and protein expression, and enhanced the transport activity of multidrug resistance-associated protein 2. A further study showed that mRNA and protein upregulation were attenuated by transient transfection of a specific constitutive androstane receptor siRNA, suggesting that the upregulation of multidrug resistance-associated protein 2 was mediated by the constitutive androstane receptor. Taken together, our findings indicate that praeruptorin A and praeruptorin C can significantly upregulate multidrug resistance-associated protein 2 expression via the constitutive androstane receptor-mediated pathway in vitro, and this should be taken as an herb-drug interaction.
Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Xunian
X
Zhou
Huichang
H
Bi
Jing
J
Jin
Lu
L
Niu
Dake
D
Cai
Rongrong
R
Deng
Yuhua
Y
Li
Yongtao
Y
Wang
Min
M
Huang
D019661:Apiaceae / Q000737:chemistry*; D000090702:Constitutive Androstane Receptor; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D056945:Hep G2 Cells; D041743:Herb-Drug Interactions; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D000090702:Constitutive Androstane Receptor; D003374:Coumarins; D004365:Drugs, Chinese Herbal; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C000715087:ABCC2 protein, human; C441070:praeruptorin A; C058808:praeruptorin C