β-Citronellol, an alcoholic monoterpene with inhibitory properties on the contractility of rat trachea

Abstract

β-Citronellol is an alcoholic monoterpene found in essential oils such Cymbopogon citratus (a plant with antihypertensive properties). β-Citronellol can act against pathogenic microorganisms that affect airways and, in virtue of the popular use of β-citronellol-enriched essential oils in aromatherapy, we assessed its pharmacologic effects on the contractility of rat trachea. Contractions of isolated tracheal rings were recorded isometrically through a force transducer connected to a data-acquisition device. β-Citronellol relaxed sustained contractions induced by acetylcholine or high extracellular potassium, but half-maximal inhibitory concentrations (IC50) for K+-elicited stimuli were smaller than those for cholinergic contractions. It also inhibited contractions induced by electrical field stimulation or sodium orthovanadate with pharmacologic potency equivalent to that seen against acetylcholine-induced contractions. When contractions were evoked by selective recruitment of Ca2+ from the extracellular medium, β-citronellol preferentially inhibited contractions that involved voltage-operated (but not receptor-operated) pathways. β-Citronellol (but not verapamil) inhibited contractions induced by restoration of external Ca2+ levels after depleting internal Ca2+ stores with the concomitant presence of thapsigargin and recurrent challenge with acetylcholine. Treatment of tracheal rings with L-NAME, indomethacin or tetraethylammonium did not change the relaxing effects of β-citronellol. Inhibition of transient receptor potential vanilloid subtype 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1) receptors with selective antagonists caused no change in the effects of β-citronellol. In conclusion, β-citronellol exerted inhibitory effects on rat tracheal rings, with predominant effects on contractions that recruit Ca2+ inflow towards the cytosol by voltage-gated pathways, whereas it appears less active against contractions elicited by receptor-operated Ca2+ channels.

Citronellol, a monoterpene alcohol with promising pharmacological activities - A systematic review

“…The antispasmodic effect of CT on isolated ileum and tracheal contraction of rats was also described, through action on channels Ca 2+ (Sadraei et al, 2013;Vasconcelos et al, 2016). According to the authors, CT reversed the contraction of ileum induced by KCl (80 mM), electrical field stimulations (EFS) and acetylcholine (ACh, 2 μM).…”

“…Vasconcelos et al (Vasconcelos et al, 2016) showed an antispasmodic effect of (±)-CT in the tracheal contraction of rats induced by K + ((IC 50 = 120.8 µM), ACh (IC 50 = 210.7 µM), EFS (IC 50 = 240.9 µM) and sodium orthovanadate (IC 50 = 243.0 µM). When contractions were evoked by selective recruitment of extracellular Ca 2+ , (±)-CT inhibited the contractions induced by activation of voltage-operated channels, but not receptor-operated channels.…”

“…This review article presents papers that described pharmacological activities of CT relevant to use in humans. In vitro studies investigated possible antibacterial (Echeverrigaray et al, 2008;Kotan et al, 2007;Mulyaningsih et al, 2011;Ngan et al, 2012;Nostro et al, 2013), antifungal (Kim and Park, 2012;Mahmoud, 1994;Pereira et al, 2015;Shin and Lim, 2004;Viollon and Chaumont, 1994;Zore et al, 2011), anti-lice (Gonzalez-Audino et al, 2011), repellent (Michaelakis et al, 2014;Semmler et al, 2014), lipolytic (Choi, 2006), anti-allergic (Kobayashi et al, 2016), anti-inflammatory (Abe et al, 2003;Su et al, 2010) and antispasmodic (Sadraei et al, 2013;Vasconcelos et al, 2016) properties. In vivo studies investigated possible cardiovascular (Bastos et al, 2009;Igor A C Menezes et al, 2010;Ribeiro-Filho et al, 2016), antidiabetic (Jagdale et al, 2016;Srinivasan and Muruganathan, 2016), anti-cholesterol (Batubara et al, 2015), antinociceptive (Brito et al, 2012;Renan G Brito et al, 2013), antihyperalgesic (Renan G , anti-anxiety (Umezu et al, 2002) and anticonvulsant (Sousa et al, 2006) activities.…”

“…Most of the in vitro studies did not describe the isomeric form of CT used in the study. Among those which did describe the isomeric form, 3 reported using only the isomeric form (±) (Mulyaningsih et al, 2011;Su et al, 2010;Vasconcelos et al, 2016), 1 used (+) and (-) (Ngan et al, 2012), and 1 used the (+), (-) and (±) forms (Kobayashi et al, 2016). In vivo studies mainly used the form (-) in studies that aimed to investigate antinociceptive and antihyperalgesic activities (Brito et al, 2012;Renan G Brito et al, 2015), (±) in studies investigating cardiovascular activities (Bastos et al, 2009;Igor A C Menezes et al, 2010) and (+) for anticonvulsant activity (Sousa et al, 2006).…”

Effects of passive inhalation of cigarette smoke on structural and functional parameters in the respiratory system of guinea pigs

“…The tension applied to each tracheal segment was set at 1 gf. The equilibration period was 1 h, and the incubation liquid was changed every 15 min 20 . After the stabilization period, concentration-effect curves were constructed for potassium (10-120 mM) and for carbachol (0.001-10 µM), with a 5 min-interval at each concentration.…”