title: Cree antidiabetic plant extracts display mechanism-based inactivation of CYP3A4.
abstract: Seventeen Cree antidiabetic medicinal plants were studied to determine their potential to inhibit cytochrome P450 3A4 (CYP3A4) through mechanism-based inactivation (MBI). The ethanolic extracts of the medicinal plants were studied for their inhibition of CYP3A4 using the substrates testosterone and dibenzylfluorescein (DBF) in high pressure liquid chromatography (HPLC) and microtiter fluorometric assays, respectively. Using testosterone as a substrate, extracts of Alnus incana, Sarracenia purpurea, and Lycopodium clavatum were identified as potent CYP3A4 MBIs, while those from Abies balsamea, Picea mariana, Pinus banksiana, Rhododendron tomentosum, Kalmia angustifolia, and Picea glauca were identified as less potent inactivators. Not unexpectedly, the other substrate, DBF, showed a different profile of inhibition. Only A. balsamea was identified as a CYP3A4 MBI using DBF. Abies balsamea displayed both NADPH- and time-dependence of CYP3A4 inhibition using both substrates. Overall, several of the medicinal plants may markedly deplete CYP3A4 through MBI and, consequently, decrease the metabolism of CYP3A4 substrates including numerous medications used by diabetics.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, ON, Canada.
authors.forename: Teresa W
authors.initials: TW
authors.lastname: Tam
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: John T
authors.initials: JT
authors.lastname: Arnason
authors.forename: Anthony
authors.initials: A
authors.lastname: Krantis
authors.forename: William A
authors.initials: WA
authors.lastname: Staines
authors.forename: Pierre S
authors.initials: PS
authors.lastname: Haddad
authors.forename: Brian C
authors.initials: BC
authors.lastname: Foster
mesh_terms: D000529:Complementary Therapies / Q000379:methods; D051544:Cytochrome P-450 CYP3A / Q000502:physiology*; D065692:Cytochrome P-450 CYP3A Inhibitors; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D058611:Horticultural Therapy / Q000379:methods; D006801:Humans; D039321:Hydrastis; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007198:Indians, North American; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry / Q000502:physiology*; D011792:Quebec; D013379:Substrate Specificity / Q000187:drug effects / Q000502:physiology
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human