title: Effects of Panax notoginseng saponins on the activities of CYP1A2, CYP2C9, CYP2D6 and CYP3A4 in rats in vivo.
abstract: The aim of this study was to assess the influence of the Panax notoginseng saponins (PNS) on the activities of the drug-metabolizing enzymes cytochrome P450 (CYP450) 1A2, 2 C9, 2D6 and 3A4 in rats. The activities of CYP1A2, 2 C9, 2D6 and 3A4 were measured using specific probe drugs. After pretreatment for 1 week with PNS or physiological saline (control group), probe drugs caffeine (10 mg/kg; CYP1A2 activity), tolbutamide (15 mg/kg; CYP2C9 activity), metoprolol (20 mg/kg; CYP2D6 activity) and dapsone (10 mg/kg; CYP3A4 activity) were administered to rats by intraperitoneal injection. The blood was then collected at different times for ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis. The data showed that PNS exhibited an induction effect on CYP1A2 by decreasing caffeine C(max) (36.3%, p < 0.01) and AUC(0-∞) (22.77%, p < 0.05) and increasing CL/F (27.03%, p < 0.05) compared with those of the control group. Western blot analysis was used to detect the effect of PNS on the protein level of CYP1A2, and the results showed that PNS could upregulate the protein expression of CYP1A2. However, no significant changes in CYP2C9, 2D6 or 3A4 activities were observed. In conclusion, the results indicate that PNS could induce CYP1A2, which may affect the disposition of medicines primarily dependent on the CYP1A2 pathway. Our work may be the basis of related herb-drug interactions in the clinic.
authors.affiliation: Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Mengnan
authors.initials: M
authors.lastname: Qin
authors.forename: Pengzhou
authors.initials: P
authors.lastname: Hang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Zhang
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002110:Caffeine / Q000008:administration & dosage / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6 / Q000097:blood / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000097:blood / Q000378:metabolism*; D003580:Cytochromes / Q000097:blood / Q000378:metabolism*; D003622:Dapsone / Q000008:administration & dosage / Q000493:pharmacokinetics; D004789:Enzyme Activation / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000493:pharmacokinetics; D053723:Panax notoginseng / Q000737:chemistry*; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry / Q000379:methods; D013997:Time Factors; D014044:Tolbutamide / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D003580:Cytochromes; D012503:Saponins; D002110:Caffeine; D003622:Dapsone; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; C507848:CYP2C9 protein, rat; C017170:Cyp1a2 protein, rat; C465260:Cyp3a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D008790:Metoprolol