Assessment of the Cytochrome P450 (CYP) interaction potential by a hydroethanolic dry extract from Aloysia citrodora Paláu (lemon verbena)

Background Lemon verbena, Aloysia citrodora Paláu (Verbenaceae) is worldwide used due to the flavor and medicinal properties of leaves and essential oil. The leaves are used traditionally in tea or extracts for several indications e.g. insomnia. Preferred preparations are infusions or aqueous dry extracts, for which a good safety profile was reported [1]. Recently, the HMPC published a 1^st draft “Aloysia citrodora Paláu, folium” [2]. However, no extracts are listed and there was a lack of data concerning potential drug interactions.

Aim The objective of the study was to characterize Extr. Aloys. citriod. e fol. spir. sicc. (Ethanol 30 % V/V; DER native 3–5:1) with respect to the potential for CYP interaction in vitro. Therefore, the major human hepatic CYP isoenzymes were investigated according to the FDA and EMA guidance’s [3], [4].

Methods and Results In a first part, putative cytotoxicity on primary human hepatocytes was examined. Lemon verbena extract had no effect on viability of primary human hepatocytes after 72 hours of incubation (1.5–150 µg/ml). With view to a single dosage of 400 mg extract a theoretical maximum of 80 µg/ml can be achieved in vivo. Therefore, 100, 10, and 1 µg/ml were chosen to span the range of therapeutic exposure. For the test item, no biologically relevant induction of functional enzyme activities occurred for CYP1A2, CYP2B6 and CYP3A4. Results obtained by qPCR confirmed the results observed in the functional activity test: neither CYP1A2, CYP2B6, nor CYP3A4 mRNA was increased in any of the donors.

In a second part the herbal test item was investigated for its potential to inhibit the human CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 isoenzymes in pooled human liver microsomes. Finally, A. citriod. extract demonstrated only a weak to mild inhibition against the in vitro activity of the investigated CYP enzymes.

Conclusion These data in combination with the lack of induction potential demonstrates that clinically relevant drug interactions caused by A. citriod. extract are unlikely.

Publication History

Article published online:
22 June 2021

• References

• 1 Bahramsoltani R. et al. J Ethnopharmacology 2018; 222: 34-51. DOI: 10.1016/j.jep.2018.04.021.
• 2 European Union herbal monograph on Aloysia citrodora Paláu (syn. Aloysia triphylla (L’Hér.) Kuntze; Verbena triphylla L’Hér.; Lippia citriodora Kunth), folium. EMA/HMPC/376770/2019
• 3 FDA Draft Guidance for Industry: In vitro Metabolism and Transporter-Mediated Drug-Drug Interaction Studies (October 2017)
• 4 European Medicines Agency: Guideline on the Investigation of Drug Interactions, CPMP/EWP/560/95/Rev. 1 (June 2012)