Effect of pinocembrin pre-treatment on expressions of Cx43 protein and claudin 1 in myocardial ischemia cardiomyocytes of arrhythmic rats

Abstract

To investigate the effects of pinocembrin on ventricular rhythm and the expression of cardiomyocyte ligament junction protein (Cx43) and claudin 1 (ZO-1) in ischemia/reperfusion (I/R) rats. Methods: Ischemia/reperfusion (I/R) model rats (n = 15) were divided into 5 groups: IR group, control group, and 3 pinocembrin groups (3, 10 and 30 mg/kg). The serum levels of creatine kinase-MB isoenzyme (CK-MB) and troponin I (cTnI) were measured by enzyme-linked immunosorbent assay (ELISA). Changes in myocardial tissue were detected by H & E staining, while mRNA and protein levels of Cx43, ZO-1 and Kir2.1 were measured by reverse transcriotion-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Results: In pinocembrin groups, heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) levels were significantly higher compared with IR group (p < 0.05). Moreover, the extent of arrhythmia and the levels of CK-MB and cTnI in pinocembrin groups were lower relative to IR group, while Na +-K +-ATPase and Ca 2+-Mg 2+-ATPase activities, as well as Cx43 mRNA, ZO-1 mRNA, and protein levels of Cx43, ZO-1 and Kir2.1 were significantly higher than the corresponding values for IR group (p < 0.05). Conclusion: These results suggest that pinocembrin reduces ventricular arrhythmias in I/R rats by upregulation of expressions of Cx43, ZO-1 and Kir21, and inhibition of redistribution of ZO-1 and Cx43. These findings provide the basis for the clinical application of pinocembrin in the treatment of arrhythmia.

Intracellular Redistribution of Left Ventricular Connexin 43 Contributes to the Remodeling of Electrical Properties of the Heart in Insulin-resistant Elderly Rats

“…They were then washed with PBS and were incubated with 3% hydrogen peroxidase for 10 min to inhibit the endogenous peroxidase activity. In the following step, as described previously, [33][34][35][36] the samples were treated with blocking solution and washed with PBS, and then incubated with either Cx43 (1:100, sc-9059; Santa Cruz) or pCx43 (1:100; ab194928 GJA1 phospho-S368; Abcam) primary antibodies at 4C overnight. As a negative control, nonimmune IgG (1:100; cat.…”

Cardioprotective Effects of Honey and Its Constituent: An Evidence-Based Review of Laboratory Studies and Clinical Trials

“…In the atrial ligation model, pinocembrin treatment significantly ameliorates cardiac arrhythmia as indicated by improved heart rate variability, shortened atrial activation latency, and prolonged atrial effective refractory period [48,49]. In parallel, the reperfusion model also demonstrated the positive effect of pinocembrin when pinocembrin increased heart rate, mean arterial pressure, and rate-pressure product parameters in echocardiograph [50].…”

“…In terms of honey constituents, two active compounds of honey were identified, namely, chrysin and pinocembrin. Five studies used chrysin [43][44][45][46][47], and three studies used pinocembrin [48][49][50] as their subject matter.…”

“…In healthy rats, two studies investigated the antihyperlipidemic effect of honey consumption [22,38], and one study each that investigated its effect on bleeding time [40] and cardiac muscle tissue lipids [41]. In diseased rat models, a myocardial injury was introduced to rats via artery ligation in four studies [43,44,48,49], isoproterenol (ISO) injection in three studies [23,37,45], and epinephrine injection, [24] chronic hypoxia [46], Nω-nitro-L-arginine methyl ester (L-NAME) [47], and ischemia and reperfusion cycle [50] in one study each. Other cardiovascular risk factors, such as hypertriglyceridemia [25] and aging [36], were also studied in fructose-induced rats and aged rats, respectively.…”

Tropical Coronary Artery Disease and Arrhythmogenic Potentials—The Changing Pattern towards Endomyocardial Fibrosis—An Analysis

“…Pinocembrin is a major flavonoid derived from propolin, plays a role in the treatment of myocardial ischemia and reperfusion injury through its antioxidant effect, reduction of calcium overload, as well as inhibition of inflammation and myocardial cell apoptosis in animal models [82]. Pinocembrin exerts its antiarrhythmic effect by increasing the activity of Ca 2+ -Mg 2+ -ATPase, thereby maintaining cardiac channels and upregulating the expression of cardiomyocyte ligament junction proteins [83]), the Cx43 (a gap junction protein, the main connexin of cardiomyocytes), ZO-1 (Claudin-1), Kir 2.1 and suppression of the redistribution of ZO-1 and Cx43, regulated by GJA 1 and KCNJ 2 genes to maintain the synchronization of electrical activity of the body and the development of heart [84]. 9) Levosimendan The clinically used inotropes worsen the reperfusion stunning and provoke arrhythmias by increasing the cytosolic calcium level.…”