Polydatin Attenuates Isoproterenol-induced Pathological Cardiac Hypertrophy via miR-214/FOXO3/NFAT Axis
Year: 2026
Type: article
Abstract: Aim: Pathological cardiac hypertrophy precedes heart failure and alters myocardial structure, function, and molecular signaling.miRNAs, particularly miR-214, regulate key remodeling and hypertrophic pathways.Although polydatin has reported cardioprotective effects, whether these involve miRNA-mediated mechanisms is unclear.This study investigates the potential role of the miR-214/Forkhead box O3 (FOXO3)/nuclear factor of activated T-cells (NFAT) axis in mediating polydatin's effects. Materials and Methods:Male Wistar rats were divided into three groups: Control, isoproterenol (ISO), 5 mg/kg/day, s.c.), and ISO + polydatin (100 mg/kg/day, oral).Following four-weeks treatment, cardiac hypertrophy was assessed by measuring heart weight, heart weight/body weight ratio, and heart weight/tibia length ratio.For molecular analyses, the expression levels of miR-1, miR-214, and miR-133b, as well as the mRNA levels of FOXO3, NFAT, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP), were measured by real-time polymerase chain reaction.Results: Morphological parameters were significantly increased in the ISO group compared with controls (p<0.001) and were markedly suppressed by polydatin (p<0.05).Among the miRNAs, only miR-214 was significantly upregulated by ISO (p=0.006), and this effect was attenuated by polydatin (p=0.030).ISO downregulated FOXO3 (p=0.027) and upregulated NFAT (p<0.001),effects that were reversed by polydatin.Expression of fetal gene markers ANP (p=0.029) and BNP (p=0.002) was markedly elevated in the ISO group, but these increases were abolished with polydatin treatment (p>0.05 vs. control). Conclusion:Polydatin demonstrates cardioprotective effects against ISO-induced pathological cardiac hypertrophy.These effects involve not only morphological improvements but also molecular regulation via the miR-214/FOXO3/NFAT axis and suppression of the fetal gene program.These findings suggest that polydatin may have potential as a pharmacological agent for preventing pathological cardiac remodeling.
Source: Namık Kemal Tıp Dergisi
Institution: Trakya University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7164917130