Gastrodin Regulates Cardiac Arrhythmia by Targeting the Gap Junction Alpha-1 Protein after Ischemia-Reperfusion

Abstract

The effects of Gastrodin (GD) on cerebral ischemia stimulated researchers to investigate its possible role in the progression of arrhythmia associated with cardiac ischemia-reperfusion (IR) damage in rats. 40 Sprague-Dawley rats were divided into four groups: Sham, Model, GD 50 mg/kg, and GD 100 mg/kg. Myocardial ischemia (MI) was caused by the procedure of ligating the left coronary artery, followed by reperfusion. Heart rate (HR), mean arterial pressure (MAP), and rate pressure product (RPP) in rats were assessed before and after ischemia and reperfusion, as well as cardiac arrhythmia in experimental rats. The I/R damage was evaluated by measuring levels of Na ⁺-K⁺ATPase and Ca²⁺-Mg²⁺ATPase, Creatine Kinase-MB (CK-MB), Cardiac Troponin I (cTnI), Gap Junction α-1 (GJα-1), Phospho-GJα-1/total-GJα-1, Kir2.1, Bax, Bcl-2, and oxidative indicators. MGL’s Autodock and Vina programs were used for in silico docking studies to identify possible interactions between GJα-1 and Gastrodin. The animals in the model group expressed a substantial decrease in HR, MAP, and RPP compared to the Sham group. GD-treated rats revealed slightly higher values compared to the model group. Expression of CK-MB and cTnI was reduced, and Na⁺-K⁺ATPase and Ca²⁺-Mg²⁺ATPase expression was increased on GD pre-conditioning. Phospho-Cx43/total-Cx43 ratio and Bax expression were increased, whereas GD reduced Bcl-2 expression. In silico molecular docking studies suggested the potential binding of GD with the GJα-1 protein, thus confirming the in vivo results. GD corrected the arrhythmia in rats subjected to I/R injury by increasing Na⁺-K⁺ATPase and Ca²⁺-Mg²⁺ATPase expression, targeting GJα-1, and modulating the expression of Kir2.1.