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Background: The consumption of botanical dietary supplements (BDS) is a common practice among the US population. However, the potential for botanical-drug interactions exists, and their mechanisms have not been thoroughly studied. CYP3A4 is an important enzyme that contributes to the metabolism of about 60% of clinically used drugs.
Purpose: To investigate the potential for botanical-drug interactions of Lepidium meyenii Walpers (maca) root and Euterpe oleracea Mart. (açaí) berries, two commonly used BDS, when co-administered with CYP3A4-metabolized drugs.
Methods: In an attempt to decrease the general discrepancy between in vivo and in vitro studies, the absorption profiles, particularly for passive diffusion, of plant extracts were investigated. Specifically, the parallel artificial membrane permeability assay (PAMPA) model was utilized to simulate intestinal filtration of passively diffused constituents of açaí and maca extracts. These were subsequently screened for in vitro liver CYP3A4 inhibition and induction. In the inhibition assay, midazolam was used as the probe substrate on genotyped human liver microsomes (CYP3A5 null), and the production of its 1'-substituted metabolite when co-cultured with extract treatments was monitored. In the induction assay, extract treatments were applied to human primary hepatocytes, and quantitative PCR analysis was performed to determine CYP3A4 mRNA expression.
Results: Passively diffused constituents of the methanol açaí extract (IC of 28.03 µg/µl) demonstrated the highest inhibition potential, and, at 1.5 µg/µl, induced significant changes in CYP3A4 gene expression. The composition of this extract was further investigated using the chemometric tool Mass Profiler Professional (MPP) on liquid chromatography-mass spectroscopy (LC-MS) data. Subsequently, five compounds of interest characterized by high abundance or high permeability were extracted for further study. This included efforts in effective passive permeability determination and structural elucidation by tandem mass spectrometry (MS/MS).
Conclusion: The passively absorbable portion of a methanol açaí extract exhibited inhibition and induction effects on CYP3A4 suggesting the potential to produce botanical-drug interactions.
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http://dx.doi.org/10.1016/j.phymed.2019.152915 | DOI Listing |
J Diet Suppl
December 2024
Division of Translational Toxicology, National Institute of Environmental Health Sciences, Durham, NC, USA.
Botanical supplements, herbal remedies, and plant-derived products are used globally. However, botanical dietary supplements are rarely subjected to robust safety testing unless there are adverse reports in post-market surveillance. Botanicals are complex and difficult to assess using current frameworks designed for single constituent substances (e.
View Article and Find Full Text PDFRegul Toxicol Pharmacol
November 2024
USP Botanical Dietary Supplements Admission Evaluation and Labeling Expert Committee, United States Pharmacopeial Convention (USP), Rockville, MD, USA; Procter & Gamble Company, 8700 Mason-Montgomery Rd, Box 2006, Cincinnati, OH, 45040, USA.
Botanical supplements and herbal products are widely used by consumers for various purported health benefits, and their popularity is increasing. Some of these natural products can have adverse effects on liver function and/or interact with prescription and over-the-counter (OTC) medications. Ensuring the safety of these readily available products is a crucial public health concern; however, not all regulatory authorities require premarket safety review and/or testing.
View Article and Find Full Text PDFFront Pharmacol
August 2024
Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
Prolonged exposure to stress is a risk factor for the onset of several disorders. Modern life is burdened by a pervasive prevalence of stress, which represents a major societal challenge requiring new therapeutic strategies. In this context, botanical drug-based therapies can have a paramount importance.
View Article and Find Full Text PDFFront Pharmacol
August 2024
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Thymic atrophy marks the onset of immune aging, precipitating developmental anomalies in T cells. Numerous clinical and preclinical investigations have underscored the regulatory role of spores (GLS) in T cell development. However, the precise mechanisms underlying this regulation remain elusive.
View Article and Find Full Text PDFFront Pharmacol
June 2024
State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an, China.
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