Identification of eugenol as the major determinant of GABAA-receptor activation by aqueous Syzygium aromaticum L. (clove buds) extract

- Activation of human α1β2-GABAA receptor by spice extracts was investigated in vitro.
- GABAA receptors are an emerging drug target for analgesic effects.
- Aqueous clove bud extracts showed highest potentiation of GABA activity.
- Eugenol was the main contributor of the GABAergic activity of the clove extract.
- Acetyleugenol was even more active than eugenol, but only present in trace amounts.

The spice Syzygium aromaticum L. (clove buds) exerts topical anesthetic and analgesic effects. Since GABAA receptors are an emerging drug target for pain treatment, the effects of aqueous clove extracts on the human α1β2-GABAA receptor were tested by two-electrode voltage clamp technique applying a three-step test system. The extract significantly and specifically potentiated the GABA-induced currents by an allosteric mechanism in concentration-dependent manner (0.5-5 µg/mL; up to 426 ± 23%). HPLC-based activity-guided fractionation revealed eugenol as main determinant of this GABAergic activity. Acetyleugenol, an important component of clove bud oil, showed even higher activity than eugenol (1 µg/mL; 308 ± 26% versus 234 ± 29%), but was detected in the aqueous extract only in trace amounts. Thus, the analgesic effects of clove might be partially mediated by positive modulation of the GABAA receptor and eugenol is a major contributor to this activity.

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