Effects ofCurcuma xanthorrhizaExtracts and Their Constituents on Phase II Drug-metabolizing Enzymes Activity.
BACKGROUND
Curcuma xanthorrhizais a native Indonesian plant and traditionally utilized for a range of illness including liver damage, hypertension, diabetes, and cancer.


OBJECTIVE
The study determined the effects ofC. xanthorrhizaextracts (ethanol and aqueous) and their constituents (curcumene and xanthorrhizol) on UDP-glucuronosyltransferase (UGT) and glutathione transferase (GST) activities.


METHODS
The inhibition studies were evaluated both in rat liver microsomes and in human recombinant UGT1A1 and UGT2B7 enzymes. p-nitrophenol and beetle luciferin were used as the probe substrates for UGT assay while 1-chloro-2,4-dinitrobenzene as the probe for GST assay. The concentrations of extracts studied ranged from 0.1 to 1000 μg/mL while for constituents ranged from 0.01 to 500 μM.


RESULTS
In rat liver microsomes, UGT activity was inhibited by the ethanol extract (IC50=279.74 ± 16.33 μg/mL). Both UGT1A1 and UGT2B7 were inhibited by the ethanol and aqueous extracts with IC50values ranging between 9.59-22.76 μg/mL and 110.71-526.65 μg/Ml, respectively. Rat liver GST and human GST Pi-1 were inhibited by ethanol and aqueous extracts, respectively (IC50=255.00 ± 13.06 μg/mL and 580.80 ± 18.56 μg/mL). Xanthorrhizol was the better inhibitor of UGT1A1 (IC5011.30 ± 0.27 μM) as compared to UGT2B7 while curcumene did not show any inhibition. For GST, both constituents did not show any inhibition.


CONCLUSIONS
These findings suggest thatC. xanthorrhizahave the potential to cause herb-drug interaction with drugs that are primarily metabolized by UGT and GST enzymes.


CONCLUSIONS
Findings from this study would suggest which ofCurcuma xanthorrhizaextracts and constituents that would have potential interactions with drugs which are highly metabolized by UGT and GST enzymes. Further clinical studies can then be designed if needed to evaluate thein vivopharmacokinetic relevance of these interactionsAbbreviations Used: BSA: Bovine serum albumin, CAM: Complementary and alternative medicine, cDNA: Complementary deoxyribonucleic acid, CDNB: 1-Chloro-2,4-dinitrobenzene, CuSO4.5H2O: Copper(II) sulfate pentahydrate, CXEE:Curcuma xanthorrhizaethanol extract, CXAE:Curcuma xanthorrhizaaqueous extract, GC-MS: Gas chromatography-mass spectroscopy, GSH: Glutathione, GST: Glutathione S-transferase, KCl: Potassium chloride, min: Minutes, MgCl2: Magnesium chloride, mg/mL: Concentration (weight of test substance in milligrams per volume of test concentration), mM: Milimolar, Na2CO3: Sodium carbonate, NaOH: Sodium hydroxide, nmol: nanomol, NSAIDs: Non-steroidal antiinflammatory drug, p-NP: para-nitrophenol, RLU: Relative light unit, SEM: Standard error of mean, UDPGA: UDP-glucuronic acid, UGT: UDP-glucuronosyltransferase.
Centre for Drug Research, Universiti Sains, Penang, Malaysia.
Nurul Afifah Mohd
NA
Salleh
Centre for Drug Research, Universiti Sains, Penang, Malaysia.
Sabariah
S
Ismail
Centre for Drug Research, Universiti Sains, Penang, Malaysia.
Mohd Rohaimi
MR
Ab Halim
Curcuma xanthorrhiza; UDP-glucuronosyltransferase; glutathione transferase; xanthorrhizol
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