@article {78, title = {Inhibitory Effects of Ficus deltoidea Extracts on UDP-glucuronosyltransferase and Glutathione S-transferase Drug-Metabolizing Enzymes}, journal = {Pharmacognosy Research}, volume = {11}, year = {2019}, month = {August 2019}, pages = {210-218}, type = {Original Article}, chapter = {210}, abstract = {

Background: Mas cotek or Ficus deltoidea is conventionally used to treat various diseases and often consumed with other medication and this may give rise to herb{\textendash}drug interaction. The potential of F. deltoidea for interactions with drug-metabolizing enzymes of UDP-gucuronosytranserase (UGT) and glutathione S-transferase (GST) have not been investigated. Objectives: We had evaluated the potential of methanol, ethanol, and aqueous extracts of F. deltoidea to cause UGT- and GST-mediated herb{\textendash}drug interaction in vitro. Materials and Methods: The total phenolic content and total phenolic content were determined using modified colorimetric method. In the UGT study, para-nitrophenol (p-NP) was employed as a substrate to determine the UGT enzymes activity in rat liver microsomes (RLM) and human liver microsomes (HLM). For the GST study, 1-chloro-2,4-dinitrobenzene was employed as a substrate to determine GST activity in rat liver cytosolic fraction. Results: The total phenolic content in F. deltoidea extracts can be ranked as follows: Methanol extract \> aqueous extract \> ethanol extract, whereas the content of flavonoid compounds in F. deltoidea extracts can be ranked as: Methanol extract \> ethanol extract \> aqueous extract. Assessment using the UGT enzymes of RLM (IC50 [Half-maximal inhibitory concentration] = 881.40 {\textpm} 1.14 μg/mL) and HLM (IC50 = 63.44 {\textpm} 1.20 μg/mL) showed that the methanol extract of F. deltoidea significantly inhibited p-NP glucuronidation compared with ethanol and aqueous extracts. For GST inhibition study, methanol extract strongly inhibited GST activity (IC50 = 70.73 {\textpm} 1.07 μg/mL), whereas no IC50 values were determined for ethanol and aqueous extracts. Conclusion: The methanol extract of F. deltoidea containing the highest flavonoid content highlights the possibility of herb{\textendash}drug interaction through the modulation of p-NP UGT and GST activity.

}, keywords = {1-chloro-2, 4-dinitrobenzene, Ficus deltoideia, Glutathione S-transferases, Herb{\textendash}drug interactions, P-nitrophenol, Uridine 5{\textquoteright}-diphospho Glucuronosyltransferases.}, doi = {10.4103/pr.pr_2_19}, author = {Mohd Halimhilmi Zulkiffli and Norliyana Mohd Salleh and Roziahanim Mahmud and Sabariah Ismail} } @article {523, title = {Effects of Curcuma xanthorrhiza Extracts and Their Constituents on Phase II Drug-metabolizing Enzymes Activity}, journal = {Pharmacognosy Research}, volume = {8}, year = {2016}, month = {August 2016}, pages = {309-315}, type = {Original Article}, chapter = {309}, 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 {\textpm} 16.33 μg/mL). Both UGT1A1 and UGT2B7 were inhibited by the ethanol and aqueous extracts with IC50 values ranging between 9.59{\textendash}22.76 μg/mL and 110.71{\textendash}526.65 μg/Ml, respectively. Rat liver GST and human GST Pi-1 were inhibited by ethanol and aqueous extracts, respectively (IC50 = 255.00 {\textpm} 13.06 μg/mL and 580.80 {\textpm} 18.56 μg/mL). Xanthorrhizol was the better inhibitor of UGT1A1 (IC50 11.30 {\textpm} 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.

}, keywords = {Curcuma xanthorrhiza, Glutathione transferase, UDP-glucuronosyltransferase, Xanthorrhizol}, doi = {10.4103/0974-8490.188873}, author = {Nurul Afifah Mohd Salleh and Sabariah Ismail and Mohd Rohaimi Ab Halim} } @article {548, title = {Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5{\textquoteright}-diphospho-glucuronosyltransferase isoforms}, journal = {Pharmacognosy Research}, volume = {7}, year = {2015}, month = {October 2015}, pages = {341-349}, type = {Original Article}, chapter = {341}, abstract = {

Background: Glucuronidation catalyzed by uridine 5{\textquoteright}-diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. Objectives: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms. Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 {\textpm} 1.51 μM followed by buprenorphine with an IC50 value of 73.22 {\textpm} 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 {\textpm} 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 {\textpm} 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 {\textpm} 1.30, 26.44 {\textpm} 1.31, and 27.28 {\textpm} 1.18 μM. Conclusion: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are

}, keywords = {4-methylumbelliferone, 7-hydroxymitragynine, Buprenorphine, Glucuronidation, Ketamine, Mitragynine.}, doi = {10.4103/0974-8490.159580}, author = {Munirah Haron and Sabariah Ismail} } @article {855, title = {Brine shrimp Lethality and Acute Oral Toxicity Studies on Swietenia mahagoni (Linn.) Jacq. seed Methanolic Extract}, journal = {Pharmacognosy Research}, volume = {2}, year = {2010}, month = {September 2010}, pages = {215-220}, type = {Original Article}, chapter = {215}, abstract = {

Background: The seeds of Swietenia mahagoni have been applied in folk medicine for the treatment of hypertension, diabetes, malaria, amoebiasis, cough, chest pain, and intestinal parasitism. Here we are the first to report on the toxicity of the Swietenia mahagoni crude methanolic (SMCM) seed extract. Methods: SMCM seed extract has been studied for its brine shrimp lethality and acute oral toxicity, in mice. Results: The brine shrimp lethality bioassay shows a moderate cytotoxicity at high concentration. The LC50 for the extract is 0.68 mg/ml at 24 hours of exposure. The LD50 of the SMCM seed extract for acute oral toxicity in mice is greater than 5000 mg/kg. Conclusion: This study demonstrates that Swietenia mahagoni crude methanolic seed extract may contain bioactive compounds of potential therapeutic significance which are relatively safe from toxic effects, and can compromise the medicinal use of this plant in folk medicine.

}, keywords = {Acute oral toxicity, Brine shrimp, Swietenia mahagoni seeds}, doi = {10.4103/0974-8490.69107}, author = {Geethaa Sahgal and Surash Ramanathan and Sreenivasan Sasidharan and Mohd Nizam Mordi and Sabariah Ismail and Sharif Mahsufi Mansor} }