Pelargonidin Inhibits Isoproterenol Induced Myocardial Fibrosis via Regulating Transforming Growth Factor-beta/Smad2/3 Signaling and Th2 Cytokines in Mice.

Pelargonidin, a natural anthocyanidin, is known for its anti-inflammatory, antioxidant, and cytoprotective properties, however its role in myocardial fibrosis remains unclear. This study explored the therapeutic potential of pelargonidin in a mouse model of isoproterenol (ISO)-induced myocardial fibrosis. Male C57BL/6 mice were treated with ISO and subsequently administered either a low (20 mg/kg/day) or high (40 mg/kg/day) dose of pelargonidin, with captopril (15 mg/kg/day) serving as a reference control. Histological analysis revealed that pelargonidin significantly reduced collagen deposition in the myocardium in a dose-dependent manner. Molecular assessments showed decreased protein expression of alpha-SMA, COL3A1, and FN1, along with downregulation of TGF-beta/Smad2/3 signaling, as evidenced by reduced levels of TGF-beta and phosphorylated Smad2/3. Additionally, pelargonidin suppressed the expression of extracellular matrix-related genes and decreased circulating levels of Th2 cytokines IL-4 and IL-13. These findings indicate that pelargonidin mitigates myocardial fibrosis by targeting the TGF-beta/Smad2/3 pathway and modulating Th2-mediated immune responses. Overall, the results suggest that pelargonidin may serve as a promising therapeutic agent for myocardial fibrosis and related cardiovascular disorders. Key words Pelargonidin " Myocardial fibrosis " Transforming Growth Factor-beta " Extracellular matrix " Cytokines.