Myocardial fibrosis is a pathological process characterized by excessive accumulation of extracellular matrix in myocardial interstitial spaces. Myocardial fibrosis is a fundamental process in ventricular remodeling and a primary contributor to the progression of heart failure. Liquiritigenin (LQ) is a flavanone compound with anti‑oxidative, anti‑carcinogenic, anti‑inflammatory and estrogenic properties. The present study aimed to investigate the regulatory potential of LQ treatment in a mouse model of isoprenaline (ISO)‑induced cardiac fibrosis and in cultured H9C2 cardiomyocytes stimulated with angiotensin II (Ang II). The treatment of ISO‑induced mice with LQ significantly decreased the levels of cardiac injury‑related proteins in the serum and ECM accumulation in mouse heart tissues. LQ treatment also effectively alleviated cardiac dysfunction in ISO‑treated mice. Further analyses revealed that LQ inhibited ISO‑induced collagen formation and activation of the transforming growth factor‑β1 (TGF‑β1)/Smad2 and protein kinase B (AKT)/extracellular signal‑regulated kinase (ERK) signaling pathways. As a major pathological event in myocardial fibrosis, the apoptosis of cardiomyocytes has been considered a key mechanism contributing to impaired left ventricle performance. The pretreatment of rat cardiomyocytes with LQ significantly reduced the apoptosis of H9C2 cells, and inhibited Ang II‑induced activation of the TGF‑β1/Smad2 and AKT/ERK pathways. In conclusion, the present study revealed that LQ ameliorated ISO‑induced myocardial fibrosis in mice and inhibited the apoptosis of cardiomyocytes in vitro by inhibiting the TGF‑β1/Smad2 and AKT/ERK signaling pathways. These results suggested the anti‑fibrotic and cardioprotective potential of LQ in fibrosis, thus supporting the use of LQ for the management of cardiomyocyte injury and myocardial fibrosis in patients with cardiac diseases.
Keywords: Smad2; extracellular signal‑regulated kinase; liquiritigenin; myocardial fibrosis; protein kinase B; transforming growth factor β1; ultrasound imaging.