@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} }