Neuromuscular System of Nematodes Is a Target of Synergistic Pharmacological Effects of Carvacrol and Geraniol

Background: The active ingredients of essential plant oils appear as potentially effective antinemtodal drugs or substances that can potentiate the action of already existing anthelmintics. So far, we have verified that, aside from the direct effect on the neuromuscular system of nematodes (by inhibiting or potentiating contractility), some of them can potentiate the effects of drugs that are agonists or antagonists of nematode cholinergic receptors. Methods: In this study the antinematodal effects of geraniol and carvacrol was compared, as well as their interaction in the experimental model Caenorhabditis elegans, on the contractile properties of Ascaris suum neuromuscular preparations and on the ACR-16 nicotinic acetylcholine receptor (nAChR) of A. suum expressed in Xenopus leavis oocytes. Results: Combination of geraniol and carvacrol, showed a synergistic nematocidal effect in the tests on C. elegans, reducing the value of individual LC50 for almost 10 times. This combination also exerted a synergistic inhibitory effect on the contractions of A. suum, and significantly increased the EC50 of ACh and reduced the maximal contractile effect. The synergistic interaction of these two monoterpenes on Asu-ACR-16 nAChR expressed in Xenopus oocytes resulted in a significant decrease of the maximum current while the ACh EC50 value remained unchanged. Conclusions: Our findings bring a better understanding on the mode of action of monoterpene plant compounds. The possible application of active ingredients of essential plant oils that exhibit a synergistic anthelmintic effect represents an important basis for the development of new drugs and new therapeutic procedures.