Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes.
Rhein, an active ingredient extensively found in plants such as Aloe, Cassitora L., rhubarb and so on, has been used for a long time in China. Pharmacological tests revealed that rhein not only had a strong antibacterial action, but also may be useful in cancer chemotherapy as a biochemical modulator. Its therapeutic action and toxicity is still the subject of considerable research. With microsome incubation assays in vitro and HPLC methods, the inhibition of rat liver CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A enzymes by rhein were studied kinetically. The results showed the most inhibition of CYP2E1 by rhein (K(i) = 10 microm, mixed); CYP3A and CYP2C9 were also inhibited by rhein, K(i) = 30 microm (mixed) and K(i) = 38 microm (mixed), respectively; rhein revealed some inhibition of CYP1A2 (K(i) = 62 microm, uncompetitive) and CYP2D6 (K(i) = 74 microm, mixed). Drug-drug interactions, especially cytochrome P450 (CYP)-mediated interactions, cause an enhancement or attenuation in the efficacy of co-administered drugs. Inhibition of the five major CYP enzymes observed for rhein suggested that changes in pharmacokinetics of co-administered drugs were likely to occur. Therefore, caution should be paid to the possible drug interaction of medicinal plants containing rhein and CYP substrates.
Tang
Jing-cheng
JC
School of Chemical Biology and Pharmaceutical Science, Capital Medical University, Beijing 100069, PR China. jingcht@ccmu.edu.cn
Yang
Hua
H
Song
Xue-ying
XY
Song
Xiao-hong
XH
Yan
Shu-lian
SL
Shao
Jian-qun
JQ
Zhang
Tian-lan
TL
Zhang
Jin-nan
JN
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D000880:Anthraquinones; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; C020491:rhein