Noncompetitive Inhibition of 5-HT3 Receptors by Citral, Linalool, and Eucalyptol Revealed by Nonlinear Mixed-Effects Modeling.https://www.ncbi.nlm.nih.gov/pubmed/26669427
Jarvis GE, Barbosa R, Thompson AJ. Abstract: Citral, eucalyptol, and linalool are widely used as flavorings, fragrances, and cosmetics. Here, we examined their effects on electrophysiological and binding properties of human 5-HT3 receptors expressed in Xenopus oocytes and human embryonic kidney 293 cells, respectively. Data were analyzed using nonlinear mixed-effects modeling to account for random variance in the peak current response between oocytes. The oils caused an insurmountable inhibition of 5-HT-evoked currents (citral IC50 = 120 µM; eucalyptol = 258 µM; linalool = 141 µM) and did not compete with fluorescently labeled granisetron, suggesting a noncompetitive mechanism of action. Inhibition was not use-dependent but required a 30-second preapplication. Compound washout caused a slow (∼180 seconds) but complete recovery. Coapplication of the oils with bilobalide or diltiazem indicated they did not bind at the same locations as these channel blockers. Homology modeling and ligand docking predicted binding to a transmembrane cavity at the interface of adjacent subunits. Liquid chromatography coupled to mass spectrometry showed that an essential oil extracted from Lippia alba contained 75.9% citral. This inhibited expressed 5-HT3 receptors (IC50 = 45 µg ml(-1)) and smooth muscle contractions in rat trachea (IC50 = 200 µg ml(-1)) and guinea pig ileum (IC50 = 20 µg ml(-1)), providing a possible mechanistic explanation for why this oil has been used to treat gastrointestinal and respiratory ailments. These results demonstrate that citral, eucalyptol, and linalool inhibit 5-HT3 receptors, and their binding to a conserved cavity suggests a valuable target for novel allosteric modulators.
What is citral found in? Lemony things. Lemon myrtle, lemongrass, lemon balm, lemon, lime, and orange juice. (http://www.aromaticplantproject.com/articles_archive/lemon_citrus_scented_oils.html)
Next, linalool is found in many plants, including ginger, may chang, some laurels and basils, coriander, and lavender. (http://scholarsresearchlibrary.com/JNPPR-vol5-iss1/JNPPR-2015-5-1-6-10.pdf, https://en.wikipedia.org/wiki/Linalool) Finally, eucalyptol is found in eucalyptus, tea tree, mugwort, bay leaves, and cannabis. (http://theleafonline.com/c/science/2014/11/terpene-profile-eucalyptol/)
Are these three oils safe? It depends on the dosage. Eucalyptol is known to have caused deaths from overuse. Also, if obtaining oils from plants, one is getting other oils and substances along with those particular plants. For example, I could never recommend using cannabis for nausea and vomiting of pregnancy because of its known effects, which include an increased risk of preterm birth (http://www.pregnancy.org/article/marijuana-use-before-pregnancy-doubles-risk-of-premature-birth) and altered fetal brain development (http://www.huffingtonpost.com/2014/01/27/marijuana-while-pregnant-affects-babies-brain_n_4674820.html). On the other hand, regular food-level uses of citral (such as in lemony beverages) and linalool (ginger!) appear to be time-tested, safe home helps for nausea.