2012 ©
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Journal Publication
Title of Article Dill Shows Potential for Herb-Drug Interactions via Up-Regulation of CYP1A2, CYP2C19, SULT1A1, NAT2 and ABCB1 in Caco-2 Cells 
Date of Acceptance 21 September 2021 
Journal
     Title of Journal Pakistan Journal of Biological Sciences 
     Standard ISI 
     Institute of Journal Asian Network for Scientific Information 
     ISBN/ISSN 1028-8880 
     Volume 2022 
     Issue 25(1) 
     Month 2022
     Year of Publication 2022 
     Page 56-66 
     Abstract Background and Objective: Dill (Anethum graveolens L.) has the potential to develop as a new alternative medicine due to its pharmacological activities. However, studies into its safety regarding herb-drug interactions have been neglected. This study investigated the risk of dill-induced herb-drug interactions (HDI) by examining its effect on the expression of phase I and II drug-metabolizing enzyme and transporter genes in Caco-2 cells. Materials and Methods: Caco-2 cells (5×105 cells/well) were treated with 10 µM ketoconazole, 20 µM rifampicin or dill extract (60-240 µg mLG1 ) for 72 hrs. Cell viability was assessed using the resazurin assay and reactive oxygen species (ROS) content was determined with 2 ,7 -dichlorofluorescein diacetate. Aspartate (AST) and alanine aminotransferase (ALT) levels were measured using L-aspartate and L-alanine with "-ketoglutarate as substrate. Expression of phase I (CYP1A2, CYP2C19, CYP2D6, CYP2E1 and CYP3A4) and II (UGT1A6, SULT1A1, NAT1, NAT2 and GSTA1/2) metabolizing genes and transporters (ABCB1, ABCC2, ABCG2 and SLCO1B1) were determined by RT/qPCR. Results: All tested concentrations of dill did not affect cell viability or AST and ALT levels. The highest concentration of dill extract (240 µg mLG1 ) significantly lowered the ROS level. Expression of CYP1A2, CYP2C19, SULT1A1, NAT2 and ABCB1 mRNA was significantly up-regulated by dill extract. Conclusion: Dill extract did not directly damage Caco-2 cells but prolonged use of dill may increase the risk of HDI via the up-regulation of the drug-metabolizing genes CYP1A2, CYP2C19, SULT1A1, NAT2 and the transporter ABCB1. 
     Keyword Dill, reactive oxygen species, herb-drug interaction, phase I metabolism, phase II metabolism, transporter 
Author
635150022-6 Mr. WACHIRAWIT UDOMSAK [Main Author]
Pharmaceutical Sciences Master's Degree

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