Assessment of Tonica, an Aqueous Herbal Haematinic, in the Modulation of Rat Hepatic Microsomal CYP-Mediated Drug Metabolizing Enzymes: Implications for Drug Interactions

摘要

The effects of Tonica (TN), an herbal haematinic prepared from the stem barks of Khaya senegalensis, Mitragyna stipulosa and Kigelia africana, on the activities of hepatic microsomal cytochrome P450 (CYP) enzymes were investigated in Sprague-Dawley rats. TN was administered to rats, by oral gavage, at the normal human dose (28 mg/kg/day), 10x and 20x that dose for 6 weeks. Activities of certain hepatic CYP drug-metabolizing enzymes and pentobarbital-induced sleeping time were determined in control and TN-treated animals. There were insignificant (p>0.05) increases in the microsomal protein content (3.25-31 %) at all doses of TN in a non-dose-dependent fashion. However, there was a general insignificant attenuation of NADPH cytochrome c (P_450) reductase activity in TN-treated animals compared to control (8.9-26.1%). p-Nitrophenol hydroxylase (pNPH) activity was insignificantly (p>0.05) elevated (14.8-23%) in the TN-treated rats compared to control. The activities of aminopyrine-N-demethylase (AmD) and nitroanisole-O-demethylase (NOD) at the normal and 10x the normal dose of TN were not significantly different from controls, but at 20x the normal dose these enzyme activities were insignificantly (p>0.05) elevated above controls (11.7 and 39.8% for AmD and NOD, respectively).