title: Inhibitory effects of the medicinal herb, Thonningia sanguinea, on liver drug metabolizing enzymes of rats.
abstract: In this study we examined the effect of the aqueous extract of Thonningia sanguinea (T.S.) on 7-ethoxyresorufin O-deethylase (EROD, CYP1A1), 7-pentoxyresorufin O-dealkylase (PROD, CYP2B1/2), 7-methoxyresorufin O-demethylase (MROD, CYP1A2), aniline hydroxylase (aniline, CYP2E1), p-nitrophenol hydroxylase (PNPH, CYP2E1) and erythromycin N-demethylase (ERDM, CYP3A1) in rat liver in vitro and in vivo. Although T.S. extract increased ERDM activity in induced rat liver microsomes, it showed a dose-dependent inhibitory effect in vitro on other P450 monooxygenase activities particularly EROD and PROD, which are mediated primarily by CYP1A1 and CYP2B1/2, respectively. PROD, EROD and MROD activities were also decreased by 18%, 19% and 40%, respectively, in hepatic microsomes prepared from rats treated with T.S. extract for 3 days. Kinetic analysis of CYP activity of 3-methylchloranthrene-induced microsomes demonstrated that T.S. inhibited EROD and MROD activities by a noncompetitive and competitive mechanism, respectively. The analysis of alterations produced by T.S. on PROD kinetic parameters in phenobarbital-induced microsomes suggested that the inhibition is noncompetitive. Pretreatment of rats with T.S. prolonged pentobarbital and phenobarbital sleeping time; however, plasma phenobarbital concentration determined on awakening showed no significant difference between control and T.S.-treated rats. T.S. was also found to be a potent inhibitor of the liver cytosolic glutathione S-transferase. These data suggest that selective modulation of CYP isoenzymes by T.S. might contribute to protection of the liver from xenobiotic-induced intoxication or to alteration of the action of drug(s) concomitantly administered besides its antioxidative properties.
authors.affiliation: Laboratory of Physiology and Pharmacology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
authors.forename: M A
authors.initials: MA
authors.lastname: Gyamfi
authors.forename: N
authors.initials: N
authors.lastname: Hokama
authors.forename: K
authors.initials: K
authors.lastname: Oppong-Boachie
authors.forename: Y
authors.initials: Y
authors.lastname: Aniya
mesh_terms: D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005869:Ghana; D066298:In Vitro Techniques; D007527:Isoenzymes; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010936:Plant Extracts; D010634:Phenobarbital