Grape pomace (GP) is a solid residue generated from grapes maceration and fermentation stages in winemaking industry. Grape pomace extracts (GPEs) concentrate a complex combination of different groups of poorly extractable biologically active polyphenolic compounds such as hydroxycinnamic and hydroxybenzoic acids and flavonoids. GPE composition depends on grape varieties and extraction procedures. Previous studies showed that phenolic compounds beneficially affect cardiovascular health reducing oxidative stress and protecting cardiac cells from ischemic damage. Few studies also proposed GPEs as potential antihypertensive agents. However, while the beneficial effect of GPEs on the endothelial function is well-documented, GPEs impact on cardiac pacemaker activity remains unexplored. This study investigates the impact of a hydroalcoholic extract of Aglianico GP on cardiac rhythmicity through a dual approach: 1) in vivo evaluation of the heart beating rate of Drosophila melanogaster's larvae and 2) in vitro analysis of atrial HL-1 cardiomyocytes spontaneous electrical activity. Larvae fed with a diet containing 100 μg/mL GPE for 96 h showed a significant reduction in the cardiac beats per minute (200.9 ± 29.67, n = 20) compared with control larvae (231.0 ± 21.72, n = 20, p < 0.005), revealing a negative chronotropic effect induced by the exposure to GPE. Whole-cell current clamp experiments on HL-1 cardiomyocytes showed a significant reduction in the frequency of action potentials (APs) firing upon 48 h treatment with 25μg/mL GPE (Hz: 0.94 ± 021, n = 5) when compared to control cells (Hz: 0.56 ± 0.25, n = 5, p < 0.05). A 56% increase of the cycle length of the APs (n = 5, p < 0.01) was also observed in GPE treated cells likely reflecting a prolonged diastolic depolarization phase. Preliminary voltage-clamp experiments showed a significant reduction in the “funny” (If) current which could reasonably explain the reduction in APs frequency recorded in HL-1 cardiomyocytes upon GPE exposure. In conclusion, this study collects intriguing data showing a negative chronotropic effect induced by an extract of Aglianico GP on cardiac rhythmicity.
A slower beat: Aglianico grape pomace extract as a novel modulator of cardiac rhythmicity
De Zio, R;Pignataro, E;Certini, M;Scorza, S;Marsano, RM;Procino, G;Carmosino, M;Gerbino, A
2024-01-01
Abstract
Grape pomace (GP) is a solid residue generated from grapes maceration and fermentation stages in winemaking industry. Grape pomace extracts (GPEs) concentrate a complex combination of different groups of poorly extractable biologically active polyphenolic compounds such as hydroxycinnamic and hydroxybenzoic acids and flavonoids. GPE composition depends on grape varieties and extraction procedures. Previous studies showed that phenolic compounds beneficially affect cardiovascular health reducing oxidative stress and protecting cardiac cells from ischemic damage. Few studies also proposed GPEs as potential antihypertensive agents. However, while the beneficial effect of GPEs on the endothelial function is well-documented, GPEs impact on cardiac pacemaker activity remains unexplored. This study investigates the impact of a hydroalcoholic extract of Aglianico GP on cardiac rhythmicity through a dual approach: 1) in vivo evaluation of the heart beating rate of Drosophila melanogaster's larvae and 2) in vitro analysis of atrial HL-1 cardiomyocytes spontaneous electrical activity. Larvae fed with a diet containing 100 μg/mL GPE for 96 h showed a significant reduction in the cardiac beats per minute (200.9 ± 29.67, n = 20) compared with control larvae (231.0 ± 21.72, n = 20, p < 0.005), revealing a negative chronotropic effect induced by the exposure to GPE. Whole-cell current clamp experiments on HL-1 cardiomyocytes showed a significant reduction in the frequency of action potentials (APs) firing upon 48 h treatment with 25μg/mL GPE (Hz: 0.94 ± 021, n = 5) when compared to control cells (Hz: 0.56 ± 0.25, n = 5, p < 0.05). A 56% increase of the cycle length of the APs (n = 5, p < 0.01) was also observed in GPE treated cells likely reflecting a prolonged diastolic depolarization phase. Preliminary voltage-clamp experiments showed a significant reduction in the “funny” (If) current which could reasonably explain the reduction in APs frequency recorded in HL-1 cardiomyocytes upon GPE exposure. In conclusion, this study collects intriguing data showing a negative chronotropic effect induced by an extract of Aglianico GP on cardiac rhythmicity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
