Bioactive Peptides and Exercise Modulate the AMPK/SIRT1/PGC-1α/FOXO3 Pathway as a Therapeutic Approach for Hypertensive Rats

Peptides are fragments of fundamental protein sequences that may have health benefits in addition to basic dietary benefits. Recently, we have reported on the pharmacological benefits of alcalase potato protein hydrolysate (APPH) and bioactive peptides isolated from APPH. The aim was to evaluate the synergistic effect of exercise along with DIKTNKPVIF (DF) peptides in ameliorating hypertension in spontaneously hypertensive rat (SHR) rats. We examined ECG parameters, lipid profiles, cardiac markers, and histology, and quantified the proteins associated with fibrosis, hypertrophy, apoptosis, mitochondrial biogenesis, and longevity pathways. DF peptide administration, along with exercise, reduced the blood pressure and cardiac marker levels in serum. Furthermore, it also suppressed the expression of fibrosis markers COL1A1, CTGF, and uPA and downregulated cardiac-hypertrophy-associated markers such as calcineurin, NFATC3, GATA4, pGATA4 and BNP. Exercise synergistically increases the expression of IFG1, PI3K, and AKT cell-survival pathway proteins, along with DF administration. Moreover, AMPK/SIRT1/PGC-1α/FOXO3 pathway protein expression was increased with the combinatorial administration of DF and exercise. Our data suggest that exercise, along with DF peptides, act synergistically in alleviating hypertension by activating the mitochondrial biogenesis pathway.