Laboratório de Biofísica e Farmacologia do Coração, Departamento de Educação (Campus XII), Universidade do Estado da Bahia (UNEB), Guanambi, Bahia, Brazil; Laboratório de Cardiobiologia, Departamento de Biofísica, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Laboratório de Cardiobiologia, Departamento de Biofísica, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Life Sci. 2021 Oct 1;282:119761. doi: 10.1016/j.lfs.2021.119761. Epub 2021 Jul 1.
Eugenol is a natural compound found in the essential oils of many aromatic plants. The compound is used as a local anesthetic because of its inhibitory effect on the voltage-gated Na channels (Na), which are expressed in the nociceptive neurons. Eugenol has shown wide range of activities in the cardiovascular system; most of these activities are attributed to the modulation of voltage-sensitive Ca channels. However, its action on Na1.5, the main subtype of Na expressed in the mammalian myocardium, is unknown. The interaction of eugenol with Na1.5 could also contribute to its antiarrhythmic properties in vitro and ex vivo. We investigated the compound's effect on sodium current (I) and its possible cardiac antiarrhythmic activity.
The effect of eugenol on cardiac contractility was investigated using isolated atrium from guinea pig (for isometric force measurements). The compound's effect on I was evaluated using human embryonic cell transiently expressing human Nav1.5 and patch-clamp technique.
Eugenol caused negative inotropic and chronotropic effects in the atria. In the ex vivo arrhythmia model, eugenol decreased atrial pacing disturbance induced by ouabain. Eugenol reduced the I in a concentration-dependent manner. Furthermore, the compound left-shifted the stationary inactivation curve, delayed recovery from inactivation of the I, and preferentially blocked the channel in the inactivated state. Importantly, eugenol was able to attenuate the late sodium current. All these aspects are considered to be antiarrhythmic.
Overall, our findings demonstrate that eugenol has antiarrhythmic activity due, at least in part, to its interaction with Na1.5.
丁香酚是许多芳香植物精油中的一种天然化合物。由于其对电压门控 Na 通道（Na）的抑制作用，该化合物被用作局部麻醉剂，而 Na 通道在伤害感受神经元中表达。丁香酚在心血管系统中显示出广泛的活性；这些活性大多数归因于对电压敏感的 Ca 通道的调制。然而，其对哺乳动物心肌中主要表达的 Na1.5 的作用尚不清楚。丁香酚与 Na1.5 的相互作用也可能有助于其在体外和离体的抗心律失常特性。我们研究了该化合物对钠电流（I）的作用及其可能的心脏抗心律失常活性。
使用豚鼠分离的心房（用于等长力测量）研究丁香酚对心脏收缩力的影响。使用瞬时表达人 Nav1.5 的人胚胎细胞和膜片钳技术评估化合物对 I 的影响。
丁香酚对心房产生负性变力和变时作用。在体外心律失常模型中，丁香酚减少了哇巴因引起的心房起搏紊乱。丁香酚呈浓度依赖性降低 I。此外，该化合物使静止失活曲线左移，延迟 I 的失活恢复，并优先在失活状态下阻断通道。重要的是，丁香酚能够减轻晚期钠电流。所有这些方面都被认为具有抗心律失常作用。
总的来说，我们的发现表明，丁香酚具有抗心律失常活性，至少部分原因是其与 Na1.5 的相互作用。
