Actions of ethnobotanically selected Cree anti-diabetic plants on human cytochrome P450 isoforms and flavin-containing monooxygenase 3.
OBJECTIVE
Cree traditional medicine is commonly used concomitantly with prescribed drugs to treat health problems related to type II diabetes (T2D) that is endemic in the Cree population. However, the safety of traditional Cree medicines with respect to drug metabolism is unknown.


METHODS
Seventeen anti-diabetic plant extracts were screened for their potential inhibition of 11 isoforms of the drug-metabolizing cytochrome P450s (CYPs), and flavin-containing monooxygenase 3 (FMO3) in fluorometric plate reader assays. Comparative analyses were conducted to determine if particular extracts were more inhibitory, or if particular enzymes were more inhibited.


RESULTS
Many anti-diabetic plant extracts inhibited the CYPs, with CYP2C and 3A isoforms being most prone to inhibition. The order of inhibition for the enzymes by the Cree plant extracts was: 2C19>3A7>3A5>3A4>2C9>2C8>FMO3>1A2>2E1>19>2D6>2B6. Extracts from Rhododendron groenlandicum, Sorbus decora, and Kalmia angustifolia were identified as having strong inhibition towards many CYP isoforms.


CONCLUSIONS
These findings demonstrate that extracts from most plant species examined have the potential to affect CYP2C- and 3A4-mediated metabolism, and have the potential to affect the bioavailability and pharmacokinetics of conventional and traditional medicines during concomitant use.
Tam
Teresa W
TW
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
Liu
Rui
R
Arnason
John T
JT
Krantis
Anthony
A
Staines
William A
WA
Haddad
Pierre S
PS
Foster
Brian C
BC
D065607:Cytochrome P-450 Enzyme Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007198:Indians, North American; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008519:Medicine, Traditional; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007527:Isoenzymes; D010936:Plant Extracts; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)