Effects of Curcuma xanthorrhiza extracts and their constituents on phase ii drug-metabolizing enzymes activity

Abstract

Background:Curcuma xanthorrhiza is 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 of C. xanthorrhiza extracts (ethanol and aqueous) and their constituents (curcumene and xanthorrhizol) on UDP-glucuronosyltransferase (UGT) and glutathione transferase (GST) activities.Materials and 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 IC50 values 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 (IC50 11.30 ± 0.27 μM) as compared to UGT2B7 while curcumene did not show any inhibition. For GST, both constituents did not show any inhibition.Conclusion:These findings suggest that C. xanthorrhiza have the potential to cause herb-drug interaction with drugs that are primarily metabolized by UGT and GST enzymes.SUMMARY Findings from this study would suggest which of Curcuma xanthorrhiza extracts 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 the in vivo pharmacokinetic relevance of these interactions Abbreviations 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 xanthorrhiza ethanol extract, CXAE: Curcuma xanthorrhiza aqueous 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.

Chemical Constituents and Bioactivities of Several Indonesian Plants Typically Used in Jamu

“…These two also inhibited lipase and and worked as antioxidants at 9.1±1.1 and 57.0±4.5 mg/mL, respectively, with an IC 50 value of >16.7 mg/mL. 39) The 55, a main compound of Java turmeric, was the better inhibitor of UGT1A1 (IC 50 of 11.30±0.27 µM) as compared to the others. 40) Treatment with 55 at a dose of 10 or 25 mg/kg/d significantly reduced fasting and postprandial blood glucose levels in high fat diet (HFD)-induced obese mice.…”

Chemical Composition and Biological Activities of Essential Oils of Curcuma Species

“…Curcuma zanthorrhiza (Syn. C. xanthorrhiza ), also known as “wan-salika-linthong” in Thailand, and “temulawak”, “Javanese ginger”, or “Javanese turmeric” in Indonesia [ 108 ], is native to Indonesia and the Malay Peninsula and is cultivated in Thailand, Philippines, Malaysia, and Sri Lanka [ 141 ]. In Indonesia, C. zanthorrhiza rhizomes are utilized as food coloring, a spice, a source of starch, a dye, in cosmetics, and in traditional medicine [ 108 ].…”

“…In Indonesia, C. zanthorrhiza rhizomes are utilized as food coloring, a spice, a source of starch, a dye, in cosmetics, and in traditional medicine [ 108 ]. In traditional medicine, infusions and extracts of C. zanthorrhiza rhizome are used in treating hypertension, diabetes, constipation, fevers, diarrhea, dysentery, liver damage, gastric problems, rheumatism, haemorrhoids, skin eruptions, and some cancers [ 108 , 141 , 142 , 143 ]. The fresh rhizome or dried powder of C. zanthorrhiza is used for skin diseases in northern Thailand [ 136 ].…”

“…Curcuma zanthorrhiza EO possesses antiproliferative [ 220 ], anti-inflammatory, antidiuretic, hypotensive, antihepatotoxic, antioxidant, antibacterial, and antifungal activities [ 141 ]. The anti-inflammatory activity of C. zanthorrhiza mainly depends on its germacrone content [ 221 ].…”

Javanese Turmeric (Curcuma xanthorrhiza Roxb.): Ethnobotany, Phytochemistry, Biotechnology, and Pharmacological Activities

“…(family: Zingiberaceae) is a native Indonesian highly valuable plant locally familiar as “Temulawak” or Java turmeric. It is mainly cultivated in Indonesia and other Southeast Asian countries such as Malaysia, Thailand, Vietnam, and Phillippines [ 1 , 2 ]. Recorded in 2019, C. xanthorrhiza was cultivated in Indonesia on a massive scale with a demolished harvested area of more than 13,042,873 m 2 producing yields of 29,637,119 kg [ 3 ].…”