title: Inhibitory action of Epilobium hirsutum extract and its constituent ellagic acid on drug-metabolizing enzymes.
abstract: Epilobium hirsutum (EH) is a medicinal plant for treating various diseases. Despite its wide usage, there is no available information about its potential influences on drug metabolism. The present study was undertaken to determine the in vivo effects of EH on hepatic CYP2B, CYP2C, CYP2D, and CYP3A enzymes that are primarily involved in drug metabolism. Male Wistar rats were injected intraperitoneally with EH water extract (EHWE) and ellagic acid (EA) at a daily dose of 37.5 and 20 mg/kg, respectively, for 9 days and hepatic drug-metabolizing enzymes were assessed at activity, protein and mRNA levels. Erythromycin N-demethylase activity was inhibited by 53 and 21 % in EHWE- and EA-treated rats, respectively. Benzphetamine N-demethylase and 7-benzyloxyresorufin-O-debenzylase activities were decreased by 53 and 43 %, and 57 and 57 % in EHWE-and EA-treated rats, respectively. Moreover, protein levels of CYP2B1, CYP2C6, CYP2D2, and CYP3A1 also decreased by 55, 15, 33, and 82 % as a result of EHWE treatment of rats, respectively. Similarly, CYP2B1, CYP2C6, CYP2D2, and CYP3A1 protein levels decreased by 62, 63, 49, and 37 % with EA treatment, respectively. qRT-PCR analyses also showed that mRNA levels of these enzymes were significantly inhibited with bothEHWE and EA treatments. In conclusion, inhibition of drug clearances leading to drug toxicity because of the lowered activity and expression of drug-metabolizing enzymes might be observed in the people who used EH as complementary herbal remedy that might be contributed by its EA content.
authors.affiliation: Department of Biology, Pamukkale University, 20070, Kinikli-Denizli, Turkey.
authors.forename: Gurbet
authors.initials: G
authors.lastname: Celik
authors.affiliation: Department of Biology, Pamukkale University, 20070, Kinikli-Denizli, Turkey.
authors.forename: Aslı
authors.initials: A
authors.lastname: Semiz
authors.affiliation: Department of Biechemistry, Faculty of Science, Selcuk University, Z-11, Selcuklu, Konya, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Karakurt
authors.affiliation: Department of Pharmaceutical Botany, Faculty of Pharmacy, Ankara University, 06100, Ankara, Turkey.
authors.forename: Ayse Mine
authors.initials: AM
authors.lastname: Gencler-Ozkan
authors.affiliation: Department of Biology, Pamukkale University, 20070, Kinikli-Denizli, Turkey.
authors.forename: Sevki
authors.initials: S
authors.lastname: Arslan
authors.affiliation: Department of Biological Sciences, Joint Graduate Program in Biochemistry, Middle East Technical University, 06800, Ankara, Turkey.
authors.forename: Orhan
authors.initials: O
authors.lastname: Adali
authors.affiliation: Department of Biology, Pamukkale University, 20070, Kinikli-Denizli, Turkey. sena@pau.edu.tr.
authors.forename: Alaattin
authors.initials: A
authors.lastname: Sen
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004610:Ellagic Acid / Q000009:adverse effects* / Q000494:pharmacology*; D031666:Epilobium / Q000009:adverse effects*; D008658:Inactivation, Metabolic / Q000187:drug effects*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D010936:Plant Extracts / Q000009:adverse effects* / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010936:Plant Extracts; D004610:Ellagic Acid; D003577:Cytochrome P-450 Enzyme System; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating
keywords: CYP2B1; CYP2C6; CYP2D2; CYP3A1; Drug-metabolizing enzymes; Ellagic acid; Epilobium hirsutum; Inhibition, drug–herb interaction