Galectin-3 C-epitope, ANP, PPIA, and albumin function as drug-responsive panel biomarkers and therapeutic targets in aging and pressure overload-induced cardiac hypertrophy

Biological aging (BA) and pressure overload-induced cardiac hypertrophy (PO-CH) are marked by myocardial thickening, fibrosis, and functional decline, culminating in an increased risk of heart failure. Effective clinical management requires biomarkers that not only track disease progression but also monitor therapeutic response. Using Amalaki Rasayana (AR), a cardioprotective nutraceutical-based medicine, in rat models of BA and PO-CH, we identified a panel of serum biomarkers whose treatment-induced decline was associated with disease regression. Among them, galectin-3 emerged in both full-length and oligomeric C-epitope cleaved forms, with the latter closely linked to pathological surface remodeling. Treatment with AR and its bioactive component gallic acid (GA) suppressed extracellular galectin-3 C-epitope oligomer accumulation by inhibiting full-length galectin-3 secretion through phosphorylation-dependent mechanisms and promotion of intracellular retention. Concurrently, serum levels of atrial natriuretic peptide (ANP), cyclophilin A (PPIA), and albumin (ALB) were consistently modulated by therapy. Validation in sera from elderly individuals and cardiac hypertrophy patients responding to conventional treatments supported the translational relevance of this biomarker panel. These findings establish a novel, mechanistically grounded biomarker set—galectin-3 C-epitope, ANP, PPIA, and ALB—for monitoring therapeutic response in cardiac hypertrophy, and position AR as a promising medicinal intervention against age- and pressure-induced cardiac pathology.