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Interaction of Phyllanthus amarus extract and its lignans with human xenobiotic receptors, drug metabolizing enzymes and drug transporters. | LitMetric

Interaction of Phyllanthus amarus extract and its lignans with human xenobiotic receptors, drug metabolizing enzymes and drug transporters.

J Ethnopharmacol

National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS, 38677, United States; Department of Bio-Molecular Sciences, School of Pharmacy, The University of Mississippi, MS, 38677, United States. Electronic address:

Published: January 2025

AI Article Synopsis

Article Abstract

Ethnopharmacological Relevance: Phyllanthus amarus is ethnomedicinally used to treat gallbladder stones, kidney stones and chronic liver diseases. P. amarus is gaining popularity as an ingredient in many botanical dietary supplements.

Aim Of The Study: To evaluate the interaction of P. amarus extract and its lignans with human xenobiotic sensing receptors (PXR and AhR) and their downstream genes.

Materials And Methods: Activation of PXR and AhR was measured by reporter gene assays. Gene expression analysis was performed in hepatic (HepG2) and intestinal (LS174T) cells by RT-PCR. CYP inhibition assays were carried out in baculosomes. The inhibitory effect on the ABC transporters (P-gp and BCRP) was investigated via rhodamine-123 and Hoechst 33342 uptake assays in Caco-2 and MDR-MDCK cells. Effect on CYP3A4 and CYP1A2 enzyme activity was measured in primary human hepatocytes.

Results: P. amarus extract and its lignans activated AhR and PXR in respective reporter cells. Tested extract and lignans significantly increased CYP3A4 mRNA but inhibited CYP3A4 enzyme activity when tested in primary human hepatocytes and CYP3A4-specific baculosomes. In contrast, increased CYP1A2 mRNA was associated with increased CYP1A2 enzyme activity in hepatocytes. No inhibition of CYP1A2 activity was detected in baculosomes. A weak inhibitory effect on ABC-transporters was observed.

Conclusions: Results suggest that overconsumption of P. amarus or P. amarus-containing botanical supplements may change CYP homeostasis which could alter the pharmacokinetics of substrate drugs, thereby elevating the risk of herb-drug interactions (HDIs) when taken concomitantly with conventional medications. Further studies are warranted to strengthen the clinical relevance of these findings.

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http://dx.doi.org/10.1016/j.jep.2024.119142DOI Listing

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