Estragole blocks neuronal excitability by direct inhibition of Na+ channels

Abstract

Estragole is a volatile terpenoid, which occurs naturally as a constituent of the essential oils of many plants. It has several pharmacological and biological activities. The objective of the present study was to investigate the mechanism of action of estragole on neuronal excitability. Intact and dissociated dorsal root ganglion neurons of rats were used to record action potential and Na+ currents with intracellular and patch-clamp techniques, respectively. Estragole blocked the generation of action potentials in cells with or without inflexions on their descendant (repolarization) phase (Ninf and N0 neurons, respectively) in a concentration-dependent manner. The resting potentials and input resistances of Ninf and N0 cells were not altered by estragole (2, 4, and 6 mM). Estragole also inhibited total Na+ current and tetrodotoxin-resistant Na+ current in a concentration-dependent manner (IC50 of 3.2 and 3.6 mM, respectively). Kinetic analysis of Na+ current in the presence of 4 mM estragole showed a statistically significant reduction of fast and slow inactivation time constants, indicating an acceleration of the inactivation process. These data demonstrate that estragole blocks neuronal excitability by direct inhibition of Na+ channel conductance activation. This action of estragole is likely to be relevant to the understanding of the mechanisms of several pharmacological effects of this substance.

Anesthetic activity of plant essential oils on <i>Cyprinus carpio</i> (koi carp)

“…This finding was in good agreement with the reports of Grayer et al (34) and Hasegawa et al (35). From the previous study, methyl chavicol showed the anesthetic activity in rats by direct inhibition of sodium channels, the major cause of excitability blockade (36). Therefore, the fish anesthetic activity of OBO presented in the present study is considered to be mainly due to methyl chavicol.…”

Essential Oil of Croton zehntneri and Its Main Constituent Anethole Block Excitability of Rat Peripheral Nerve

“…Together, these findings indicate that the EOCz effects can be attributed to the action of its main constituent, anethole. However, the possible involvement of other minor constituents such as estragole (4.80 %) and 1,8-cineole (2.95 %) cannot be excluded, since these constituents also block the action potential in dorsal root and superior cervical ganglion neurons, respectively [22,24,28,29]. A partial contribution of these constituents has been previously reported for the EOCz in the mediation of antispasmodic [11], antinociceptive [4], cardiovascular [13], and skeletal muscle [15] effects.…”

“…The mechanism of this decreased excitability, which would lead to the inhibitory action on CAP generation, was not elucidated. However, several terpenes and terpenoids of small molecular weight, such as thymol, eugenol, linalool, carvacrol, and estragole, act on Na + channels [25,28,[31][32][33]. This makes the blockade of this ion channel an attractive hypothesis to explain the effect of the EOCz and anethole on nerve excitability.…”

Essential oil of Pterodon polygalaeflorus Benth attenuates nociception in mice

“…Northeastern flora is abundant in aromatic species, whose EO consist of a mix of compounds, mostly phenylpropanoic and terpene derivatives. This chemical complexity allows EO to have several biological effects, such as antiparasitic (7), antimicrobial (8), analgesic and anti-inflammatory (9), diuretic and hypotensive (10), antimalarial (11), gastro-protector (1,6), cell excitability inhibitor (12 –14), among others.…”