Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Potential of Anethum graveolens L. to up-regulate the expression of phase I and II metabolizing genes in HepG2 cells

Wachirawit Udomsak¹, Waranya Chatuphonprasert^1,2, Wipawee Tukum-mee³, Jintanaporn Wattanathorn³, Kanokwan Jarukamjorn¹

¹Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; ²Faculty of Medicine, Mahasarakham University, Mahasarakham 44000, Thailand; ³Research Institute for Human High Performance and Health Promotion, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

For correspondence:- Kanokwan Jarukamjorn Email: kanok_ja@kku.ac.th Tel:+6643202379

Accepted: 29 November 2021 Published: 30 December 2021

Citation: Udomsak W, Chatuphonprasert W, Tukum-mee W, Wattanathorn J, Jarukamjorn K. Potential of Anethum graveolens L. to up-regulate the expression of phase I and II metabolizing genes in HepG2 cells. Trop J Pharm Res 2021; 20(12):2519-2525 doi: 10.4314/tjpr.v20i12.9

© 2021 The authors.
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Abstract

Purpose: To investigate the effects of the herbal medicine Anethum graveolens L. (AG) on the expressions of phase I and II metabolizing genes in HepG2 cells in order to gain insight into the metabolism of AG.

Methods: HepG2 cells (5 x 10⁵ cells/well) were treated with either 10 µM ketoconazole, 20 µM rifampicin, or AG extract (60 - 480 µg/mL) for 72 h. Cell viability and reactive oxygen species (ROS) production were assessed using resazurin and 2′,7′-dichlorofluorescein diacetate assays, respectively. The mRNA expression of phase I (CYP1A2, CYP2C19, CYP2D6, and CYP3A4) and phase II metabolizing enzymes (UGT1A6 and NAT1) were determined using reverse transcription-real-time polymerase chain reaction (qRT-PCR).

Results: ROS production was not affected by the various treatments. The highest concentration of AG (480 µg/mL) reduced cell viability to 63.33 %. The expressions of CYP1A2, CYP2C19, CYP2D6, and NAT1 mRNA were significantly elevated after 72-h AG treatment.

Conclusion: The use of AG as an alternative medicine, particularly at high concentrations and/or after prolonged use, poses a risk for herb-drug interactions due to the up-regulation of CYP1A2, CYP2C19, CYP2D6, and NAT1 expression by AG in HepG2 cells.

Keywords: Dill, Reactive oxygen species, Metabolizing enzymes, Drug interaction, Hepatocellular carcinoma cell