Induction of cytochrome P450 and/or detoxication enzymes by various extracts of rosemary: description of specific patterns.
The ability of rosemary to modulate cytochrome P450 (CYP) and detoxication enzymes in rat liver was evaluated by comparing the effects of dried leaves and leaf extracts with different chemical compositions: essential oil (EO) containing monoterpenes, a dichloromethane extract (DCME) containing phenolic diterpenes and a water-soluble extract (WSE) containing phenolic compounds such as rosmarinic acid and flavonoids. Chemical analyses were done in order to characterize the composition of extracts. Male Wistar rats received the leaves or extracts of rosemary in their diet at 0.5% (w/w) for 2 weeks. The effects of such treatments were evaluated for CYP (1A, 2B, 2E1), glutathione S-transferase (GST), NAD(P)H: quinone reductase (QR) and UDP-glucuronosyltransferase (UGT) activities and on protein levels (immunoblot analyses). Expression of specific UGT isoforms (mRNA semi-quantification by RT-PCR) was measured. Our study reports that EO selectively induced CYP, particularly CYP2B. WSE enhanced both CYP and detoxication enzymes. DCME acted as a monofunctional inducer, inducing GST, QR and UGT, in particular UGT1A6. Considering the specific pattern of induction obtained with DCME and WSE treatment, it should be relevant to evaluate the chemopreventive potency of these extracts on carcinogenesis in animal models.
Debersac
P
P
Unité Mixte de Recherche de Toxicologie Alimentaire, Institut National de la Recherche Agronomique-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation, BP 86510, 17 rue Sully, 21065 Cedex, Dijon, France.
Heydel
J M
JM
Amiot
M J
MJ
Goudonnet
H
H
Artur
Y
Y
Suschetet
M
M
Siess
M H
MH
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018890:Chemoprevention; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D015151:Immunoblotting; D019686:Lamiaceae / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms
D010936:Plant Extracts; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System