Polydatin Attenuates Isoproterenol-induced Pathological Cardiac Hypertrophy via <i>miR-214</i>/<i>FOXO3/NFAT Axis</i>

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KORKMAZ B. E., YILDIZ M., BAL K., AVKIRAN M.

NAMIK KEMAL MEDICAL JOURNAL, cilt.14, sa.2, ss.134-143, 2026 (ESCI, TRDizin)

Özet

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.