Effects of the standardized extract of Cantella Asiatica (ECa 233) on human cytochrome P450 enzymes and phase II drug matabolizing enzymes in rats

Abstract

The standardized extract of C. asiatica (ECa 233) was shown to exhibit learning and memory enhancing effects. The purpose of this study was to investigate effects ECa 233 on major human drug-metabolizing CYPs by using recombinant human CYPs in the in vitro study. Effects of this extract on phase II drug metabolizing enzymes including UDPglucuronosyltransferase (UDPGT), sulfotransferase (SULT), glutathione S-transferase (GST) and NAD(P)H quinone oxidoreductase (NQOR) were also studied in vivo in rats. The results of the in vitro study showed that ECa 233 inhibited CYP3A4 (IC50 = 210.98 μg/ml), CYP2C19 (IC50 = 365.18 μg/ml) and CYP2B6 (IC50 = 871.14 μg/ml). ECa 233 did not affect CYP1A2 and CYP2D6 (IC50 > 1,000 μg/ml), and CYP2C9 (IC50 > 750 μg/ml). No inhibition of ECa 233 on CYP2E1 was observed at the concentration up to 250 μg/ml. This finding provided a preliminary information that ECa 233 possessed a potential effect to have an interaction with other medicines that were metabolized by CYP3A4, CYP2C19 and CYP2B6. Whether or not, this effect was clinically significant need to be further studied. To investigate effects of ECa 233 on the activities of phase II drug metabolizing enzymes. All doses (10, 100 and 1,000 mg/kg/day) of ECa 233 were orally given to both male and female Wistar rats for 90 days. The results showed that all dosage regimens of ECa 233 did not affect the activities of UDPGT, GST and NQOR as compared to the control group in both male and female rats. The activity of SULT was significantly decreased in male rats treated with ECa 233 at all doses as compared to the control group, whereas this enzyme was not changed in female rats. This study provided the information of effects of ECa 233 on phase II drug-metabolizing enzymes in animals, thus interpretation of these data from animal to human should be further studied.