Effects of Standardized Medicinal Plant Extracts on Drug Metabolism Mediated by CYP3A4 and CYP2D6 Enzymes

Abstract

The use of medicinal plants concomitantly with conventional drugs can result in herb−drug interactions that cause fluctuations in drug bioavailability and consequent therapeutic failure and/or toxic effects. The CYP superfamily of enzymes plays an important role in herb−drug interactions. Among CYP enzymes, CYP3A4 and CYP2D6 are the most relevant since they metabolize about 50% and 30% of the drugs on the market, respectively. Thus, the main goal of this study was to evaluate the occurrence of in vitro interactions between medicinal plant extracts and drug substrates of CYP3A4 and CYP2D6 enzymes. Standardized extracts from nine medicinal plants (Bauhinia forficata, Cecropia glaziovii, Cimicif uga racemosa, Cynara scolymus, Echinacea sp., Ginkgo biloba, Glycine max, Ilex paraguariensis, and Matricaria recutita) were evaluated for their potential interactions mediated by CYP3A4 and CYP2D6 enzymes. Among the extracts tested, C. glaziovii (red embauba) showed the most relevant inhibitory effects of CYP3A4 and CYP2D6 activity, while I. paraguariensis (yerba mate) inhibited CYP3A4 activity. Both extracts were chemically analyzed by UPLC-MS/MS, and these inhibitory effects could lead to clinically potential and relevant interactions with the drug substrates of these isoenzymes.

In Vitro Free Radical Scavenging Properties and Anti-Inflammatory Activity of Ilex paraguariensis (Maté) and the Ability of Its Major Chemical Markers to Inhibit the Production of Proinflammatory Mediators

“…Also, UPLC/DAD showed THEO, NCA, CCA, CGA, CAF, and RUT as the major compounds while UPLC/MS analysis confirmed these compounds and the presence of quinic acid, citric acid, caffeoylglucose, feruloylquinic acid, quercetin-glycoside, and kaempferolrhamnoglucoside. All these data are in agreement with the literature data [18,19,20,31,36]. Considering the high amounts of phenolic compounds detected in I. paraguariensis preparations, the antioxidant activity of these extracts and its chemical markers was also investigated by the DPPH assay.…”

“…Chemical Characterization by LC/MS Analysis. The LC/MS analysis was performed according Feltrin et al [31]. Briefly, the compounds were identified by highperformance liquid chromatography (Waters® Acquity™ UPLC™; catalogue number 186015018) coupled to a photodiode array detector (PDA, Waters®; catalogue number 186015033) and a high-resolution mass spectrometer (Xevo®G2 QTof, WATERS® model; catalogue number 186006532) equipped with a source of electrospray ionization (ESI) operating in positive and negative mode.…”

Pharmacognostic Evaluation of Ten Species of Medicinal Importance of Cecropia: Current Knowledge and Therapeutic Perspectives

“…While most phytochemical studies focused on identifying and isolating flavonoids, other components that have gained less attention are worth mentioning in this review. For instance, the iridoids geniposide 1 and 2 were found in the leaves of C. pachystachya and C. hololeuca [49] and the flavonolignans ent-mururin A and entvaccinin A in the leaves of C. obtusifolia [61]; the coumarins 4-ethyl-5-(n-3valeroil)-6-hexahy-drocoumarin, scopoletin [4,59], some organic acids, anthraquinones, and 1 alkaloid were also found in Cecropia species (Table 4S, Supporting Information) [59,62,63].…”

“…The results also showed that the butanol fraction and its main constituents isoorientin, orientin, isovitexin, catechin, epicatechin, and procyanidin B2, B3, B5, and C1 had equal potency inhibiting gastric H+, K+ ATPase enzyme activity, when tested both individually and in a complex mixture (Table 5S, Supporting Information) [20]. Feltrin et al showed that a standardized extract of this plant was able to inhibit 2 cytochrome P450 enzymes, namely CYP3A4 and CYPD6 (Table 5S, Supporting Information), a characteristic that may modify the bioavailability and efficacy of certain drugs [62].…”

Artischocke – Gemüsepflanze mit potenter Heilkraft

“…Interaktionen mit Medikamenten sind nicht bekannt [22], mit Coumarinderivaten aber möglich (es sollte engmaschig kontrolliert werden). In vitro interagiert der Artischocken-Wirkstoff mit CYP3A4 und CYP2D6 [10].…”