Eugenol interacts with cardiac sodium channel and reduces heart excitability and arrhythmias

Author(s)

Teixeira-Fonseca, Jorge Lucas ^{[1, 2]} ; Santos-Miranda, Artur ^[2] ; da Silva, Joab Barbosa ^[1] ; Marques, Leisiane Pereira ^{[1, 2]} ; Joviano-Santos, Julliane Vasconcelos ^[2] ; Chaves Nunes, Paula Idma ^[1] ; Roman-Campos, Danilo ^[2] ; Santana Gondim, Antonio Nei ^{[1, 2]}

Affiliation

^[1] Univ Estado Bahia UNEB, Lab Biofis & Farmacol Coracao, Dept Educ Campus 12, Guanambi, BA - Brazil

^[2] Univ Fed Sao Paulo UNIFESP, Dept Biofis, Lab Cardiobiol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 282, OCT 1 2021.
• Web of Science Citations: 0

Abstract

Aims: 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-v), 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 Ca2+ channels. However, its action on Na(v)1.5, the main subtype of Na-v expressed in the mammalian myocardium, is unknown. The interaction of eugenol with Na(v)1.5 could also contribute to its antiarrhythmic properties in vitro and ex vivo. We investigated the compound's effect on sodium current (I-Na) and its possible cardiac antiarrhythmic activity. Methods: 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-Na was evaluated using human embryonic cell transiently expressing human Na(v)1.5 and patch-clamp technique. Key findings: 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-Na in a concentration-dependent manner. Furthermore, the compound left-shifted the stationary inactivation curve, delayed recovery from inactivation of the I-Na, 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. Significance: Overall, our findings demonstrate that eugenol has antiarrhythmic activity due, at least in part, to its interaction with Na(v)1.5. (AU)

• FAPESP's process: 18/22830-9 - Involvement of the Ca2+/ Calmodulin/CAMKII signaling axis in the electrical and contractile dysfunctions of the heart in the chronic phase of Chagas Disease
• Grantee: Artur Santos Miranda
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/20777-3 - Genetic variants of the Nav 1.5 sodium channel and its therapeutic implications.
• Grantee: Julliane Vasconcelos Joviano dos Santos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/21304-4 - Arrhythmogenic mechanisms in right heart diseases
• Grantee: Danilo Roman Campos
• Support Opportunities: Regular Research Grants