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Publication
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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 |
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Reviewing Status |
มีผู้ประเมินอิสระ |
Status |
ตีพิมพ์แล้ว |
Level of Publication |
นานาชาติ |
citation |
true |
Part of thesis |
true |
ใช้สำหรับสำเร็จการศึกษา |
ไม่เป็น |
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