Liquiritigenin alleviates high-salt diet-induced heart damage by inhibiting TGF-β1/Smad signaling and reducing inflammation and fibrosis.

Excessive dietary salt intake is a major risk factor for cardiovascular disease, immune dysregulation, and metabolic syndrome, representing a growing global health challenge. A high-salt diet (HSD) induces oxidative stress, inflammation, and myocardial fibrosis, ultimately leading to cardiac injury. Nevertheless, effective preventive interventions remain limited. Liquiritigenin (LG), a natural flavonoid isolated from liquorice, possesses potent antioxidant and anti-inflammatory activities. However, its cardioprotective potential in the context of HSD-induced damage has not been fully elucidated. This study aimed to evaluate the protective effects and underlying mechanisms of LG against HSD-induced cardiac injury. An in vivo model was established by feeding male BALB/c mice a HSD, while H9c2 cardiomyocytes stimulated with 50 mM NaCl were used to confirm the findings in vitro. Cardiac injury biomarkers, including creatine kinase (CK) and lactate dehydrogenase (LDH), oxidative stress indicators such as catalase (CAT), glutathione (GSH), and malondialdehyde (MDA), inflammatory mediators, and fibrosis-related proteins were measured. LG markedly decreased serum CK and LDH, attenuated ROS accumulation, reduced MDA, and enhanced antioxidant enzyme activities. Histological analysis demonstrated reduced myocardial damage, suppressed inflammatory infiltration, and restoration of fibrosis-related protein expression. In vitro results further confirmed the anti-inflammatory and anti-fibrotic effects of LG. Mechanistically, LG inhibited HSD-induced transforming growth factor-β1 (TGF-β1) overexpression and suppressed Smad2 phosphorylation, thereby preventing inflammatory signaling and the progression of myocardial fibrosis. In conclusion, these findings identify LG as a promising cardioprotective candidate that mitigates oxidative stress, inflammation, and fibrosis through modulation of the TGF-β1/Smad signaling pathway.