Novel insights into basic research: exploring molecular effects of trans-cinnamaldehyde and eugenol on α7 and muscle acetylcholine receptors via electrophysiological assessment

HERNANDO G; CHRESTIA, J.F.; LEDA S; BOUZAT, C.

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAl 2023; 2023

Naturally occurring bioactive compound have been used in traditionalmedicine for the treatment of various diseases for many centuries.In modern times, there has been a renewed interest in naturalcompounds and essential oils for their medicinal properties. Inrecent years, it has been demonstrated that many of these naturalcompounds act on neurotransmitter receptors, including Cys-loopreceptors such as the nicotinic acetylcholine receptor (nAChR). nAChRsform a family of ACh-gated ion channels found in the centraland peripheral nervous systems, involved in processes like musclecontraction, memory, and attention. In this project, we assessed themolecular-level effects of trans-cinnamaldehyde (TC) and eugenol(EGN) -the two naturally occurring phenylpropanoids present inCinnamomum oil- on two types of mammalians nAChR, which areinvolved in several pathological disorders. As TC and EGN are multitargetdrug, there is a need to establish the molecular mechanismsby which they may exert therapeutic as well as adverse effects.Through single-channel recordings, we observed that TC exerts anegative modulatory effect on both α7 and muscular nAChR. On theone hand, TC leads to a marked reduction of α7 activity by decreasingthe frequency of activation episodes without causing changes inamplitude and in the open durations. On the other hand, recordingsfrom muscular nAChR exhibit a concentration-dependent reductionin open channel duration within the micromolar range, induced byboth TC and EGN. This change is accompanied by a shift towardsshorter durations in the main closed component. The modulation ofnAChRs is of pharmacological relevance and should be consideredin the evaluation of the potential therapeutic uses of TC and EGNas. Our findings offer insights into how natural compounds influenceCys-loop receptors, which remain unexplored and are important targetsin various therapeutic approaches.