Effects Of Curcuma Xanthorrhiza Roxb. On Phase Ii Drug Metabolizing Enzymes
Loading...
Date
2015-05
Authors
MOHD SALLEH, NURUL AFIFAH
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Curcuma xanthorrhiza is traditionally utilized for a range of illness including
liver damage, hypertension and cancer. Since the consumption of herbal health
supplements together with modern medications had increased, the risk of herb-drug
interaction may also increase. UDP-glucuronosyltransferase (UGT) and glutathione
transferase (GST) are phase II enzymes which are involved in metabolism of
numerous xenobiotic and endogenous substances. Induction or inhibition of UGT
and GST enzyme by Curcuma xanthorrhiza may affect the metabolism of drugs that
are highly metabolized by these enzymes. In this study, the effects of aqueous and
ethanol extracts of Curcuma xanthorrhiza and their three main constituents, namely
curcumene, curcumin and xanthorrhizol on UGT and GST activity in vitro were
investigated. Two in vitro models, rat liver and recombinant expressed enzyme were
employed as the enzyme sources to access the inhibition studies. In rat liver
microsome, UGT activity was inhibited by the ethanol extract with IC50 values of
279.74 ± 16.33 μg/mL. Assessment towards UGT1A1 and UGT2B7 isoforms has
shown higher inhibition by Curcuma xanthorrhiza extracts based on the IC50 values
obtained. Highest inhibitions towards both isoforms were demonstrated by ethanol
extract (IC50 for UGT1A1 = 22.76 ± 7.20 ug/mL, UGT2B7 = 9.59 ± 1.37 ug/mL) as
compared to the aqueous extract (IC50 for UGT1A1 = 110.71 ± 26.49 ug/mL,
UGT2B7 = 526.65 ± 31.65 ug/mL). Similar studies conducted using rat liver
microsome have shown no inhibition of UGT activity by Curcuma xanthorrhiza
constituents. However, curcumin and xanthorrhizol were the better inhibitors of
UGT1A1 (IC50 = 6.76 ± 2.92 μM for curcumin and 11.30 ± 0.27 μM for
xanthorrhizol) as compared to UGT2B7 (IC50 = 32.50 ± 0.26 μM for curcumin and
42.11 ± 19.84 μM for xanthorrhizol). Curcuma xanthorrhiza extracts and
constituents were screened for the inhibition of cytosolic rat liver GST, recombinant
mouse GST Mu-1 (mGSTM1) and recombinant human GST Pi-1 (hGSTP1). The
results obtained demonstrated that cytosolic rat liver GST was inhibited by ethanol
extract with IC50 value of 292.38 ± 20.16 ug/mL while mGSTM1 was strongly
inhibited by ethanol extract (IC50= 20.11 ± 2.38 ug/mL), followed by weak
inhibition by aqueous extract (IC50= 648.72 ± 51.30 ug/mL). As for hGSTP1, the
ethanol extract demonstrated the highest inhibition (IC50 = 128.88 ± 8.61 μg/mL)
while the aqueous extract demonstrated weak inhibition with an IC50 value of 726.04
± 57.35 μg/mL. Curcumin demonstrated strongest inhibition on mGSTM1 (IC50=
5.23 ± 0.29 uM) followed by hGSTP1 (IC50= 39.13 ± 6.43 μM). These findings
suggest that Curcuma xanthorrhiza has the potential to cause herb-drug interaction
with drugs or substrates that are primarily metabolized by UGT and GST enzymes.
Future studies are needed to evaluate the clinical significance of this interaction.
Description
Keywords
Effects Of Curcuma Xanthorrhiza Roxb , On Phase Ii Drug Metabolizing Enzymes