title: The influence of standardized Valeriana officinalis extract on the CYP3A1 gene expression by nuclear receptors in in vivo model.
abstract: Valeriana officinalis is one of the most popular medicinal plants commonly used as a sedative and sleep aid. It is suggested that its pharmacologically active compounds derived from the root may modulate the CYP3A4 gene expression by activation of pregnane X receptor (PXR) or constitutive androstane receptor (CAR) and lead to pharmacokinetic herb-drug interactions. The aim of the study was to determine the influence of valerian on the expression level of CYP3A1 (homologue to human CYP3A4) as well as nuclear receptors PXR, CAR, RXR, GR, and HNF-4α. Male Wistar rats were given standardized valerian extract (300 mg/kg/day, p.o.) for 3 and 10 days. The expression in liver tissue was analyzed by using real-time PCR. Our result showed a decrease of CYP3A1 expression level by 35% (P = 0.248) and 37% (P < 0.001), respectively. Moreover, Valeriana exhibited statistically significant reduction in RXR (approximately 28%) only after 3-day treatment. We also demonstrated a decrease in the amount HNF-4α by 22% (P = 0.005) and 32% (P = 0.012), respectively. In case of CAR, the increase of expression level by 46% (P = 0.023) was noted. These findings suggest that Valeriana officinalis extract can decrease the CYP3A4 expression and therefore may lead to interactions with synthetic drugs metabolized by this enzyme.
authors.affiliation: Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Marii Magdaleny 14, 61-861 Poznan, Poland ; Department of Quality Control of Medicinal Products and Dietary Supplements, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland.
authors.forename: Anna
authors.identifier: 0000-0001-5455-8315
authors.initials: A
authors.lastname: Bogacz
authors.affiliation: Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Marii Magdaleny 14, 61-861 Poznan, Poland ; Department of Quality Control of Medicinal Products and Dietary Supplements, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland.
authors.forename: Przemyslaw M
authors.initials: PM
authors.lastname: Mrozikiewicz
authors.affiliation: Department of Quality Control of Medicinal Products and Dietary Supplements, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Karasiewicz
authors.affiliation: Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Marii Magdaleny 14, 61-861 Poznan, Poland ; Department of Quality Control of Medicinal Products and Dietary Supplements, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland.
authors.forename: Joanna
authors.identifier: 0000-0002-8347-0512
authors.initials: J
authors.lastname: Bartkowiak-Wieczorek
authors.affiliation: Department of Rehabilitation, Poznan University of Medical Sciences, 28 Czerwca 1956, 61-545 Poznan, Poland.
authors.forename: Marian
authors.identifier: 0000-0002-9487-8388
authors.initials: M
authors.lastname: Majchrzycki
authors.affiliation: Department of Pharmacology, Poznan University of Medical Sciences, Rokietnicka 5a, 60-806 Poznan, Poland ; Department of Pharmacology and Biotechnology, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland.
authors.forename: Przemyslaw L
authors.initials: PL
authors.lastname: Mikolajczak
authors.affiliation: Department of Pharmacology and Biotechnology, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland ; Department of Pharmaceutical Botany and Plant Biotechnology, Poznan University of Medical Science, Marii Magdaleny 14, 61-861 Poznan, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Ozarowski
authors.affiliation: Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Marii Magdaleny 14, 61-861 Poznan, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Grzeskowiak
mesh_terms: D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014632:Valerian / Q000737:chemistry*
chemical_list: D010936:Plant Extracts; D018160:Receptors, Cytoplasmic and Nuclear; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A