The effect of a strongly basic alkaloidal fraction of Rhazya stricta, a traditional medicinal plant, on cytochrome P450-mediated metabolism of theophylline in mice.
The strongly basic alkaloidal fraction of the traditional medicinal plant Rhazya stricta (RS) was given orally to mice, in a single dose of 10 mg/kg (group 1) or, twice daily for 3 days at the same dose (group 2). A third group (control) received normal saline. Liver homogenates from all animals were used to assess the microsomal activity of cytochrome P450 and its isoforms as well as its catalytic activity (using theophylline as a substrate). RS alkaloidal fraction had no significant effect on the total amount of microsomal cytochrome P450, but it caused a significant increase in the cytochrome P450 isoforms CYPs 1A1 and 1A2. It also significantly increased the concentrations of some metabolites of theophylline. These results suggest that RS has the potential to interact with other drugs that are biotransformed by cytochrome P450, when given concomitantly with it.
El-Kadi
A O
AO
Department of Pharmacology and Toxicology, University of Western Ontario, Canada.
Tanira
M O M
MO
Ali
B H
BH
Bashir
A K
AK
Souich
P Du
PD
D000284:Administration, Oral; D000818:Animals; D029062:Apocynaceae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D013806:Theophylline / Q000493:pharmacokinetics*
D010936:Plant Extracts; D003577:Cytochrome P-450 Enzyme System; D013806:Theophylline