Effect of Boesenbergia rotunda ethanolic extract on CYP3A4, CYP2C9 and CYP2E1 activities
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Abstract
Introduction and Objectives: Fingerroot (Boesenbergia rotunda), a traditional Thai herb, has long been used in both culinary and medicinal applications within traditional Thai medicine. Recent studies have shown that ethanol extracts of B. rotunda, commonly referred to as B. rotunda liquor, exhibit various pharmacological activities with potential applications in drug development or as herbal health products, including antiviral activity against SARS-CoV-2. However, the use of B. rotunda extract products alongside conventional medications raises concerns regarding potential herb–drug interactions. These interactions may be due to the modulation of cytochrome P450 (CYP) enzymes by herbal constituents. This study aimed to investigate the effects of B. rotunda extract and its major constituents on the activities of CYP3A4, CYP2C9, and CYP2E1. These isoenzymes were selected based on their clinical significance: CYP3A4 metabolizes over 50% of marketed drugs; CYP2C9 metabolizes warfarin, a drug with a narrow therapeutic index; and CYP2E1 is involved in the metabolism of ethanol, which is widely consumed.
Methods: B. rotunda rhizomes were extracted by maceration in 95% ethanol for 72 hours, repeated three times. The chemical composition and content of active compounds in the extract were analyzed using ultra-performance liquid chromatography (UPLC). The inhibitory effects of the extract on CYP3A4, CYP2C9, and CYP2E1 enzymes were evaluated by measuring the fluorescence of metabolites formed during enzyme-substrate reactions. Inhibitory activities of both the crude extract and its major constituents were compared to a negative control (0.25% DMSO) and known positive CYP inhibitors: ketoconazole (CYP3A4), sulfaphenazole (CYP2C9), and tranylcypromine (CYP2E1). The results were presented as percentage inhibition (% inhibition) and IC50 values. Statistical analyses were performed to assess the significance of differences observed.
Results: The major active compounds identified in the ethanol extract of B. rotunda were pinocembrin and pinostrobin, with contents of 6.0% and 12.0% w/w of the dried extract, respectively. The concentrations of pinocembrin and pinostrobin in the tested extract were 11.71 µM and 22.20 µM, respectively. The ethanol extract demonstrated inhibitory activity against CYP3A4 and CYP2C9 but not against CYP2E1. Among the individual constituents, pinocembrin significantly inhibited CYP3A4 (p = 0.037) at the concentration found in the extract, whereas pinostrobin showed no such effect. Neither compound inhibited CYP2C9 or CYP2E1 activity.
Discussion: The inhibitory effect of the ethanol extract on CYP3A4 activity was concentration-dependent and attributed, at least in part, to the presence of pinocembrin. Pinostrobin did not contribute to this inhibition. The observed inhibition of CYP2C9 by the extract is likely due to other constituents besides pinocembrin and pinostrobin. No significant inhibition of CYP2E1 activity was observed for either the extract or its major constituents.
Conclusion and Recommendations: The ethanol extract of B. rotunda inhibits CYP3A4 activity, with pinocembrin being a contributing factor. The inhibition of CYP2C9 activity by the extract does not appear to involve either pinocembrin or pinostrobin. No inhibitory effects on CYP2E1 were observed for the extract or its major compounds. Further research is recommended to elucidate the specific mechanisms of enzyme inhibition and to conduct clinical studies to evaluate potential herb–drug interactions.
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