Abstract
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.
Highlights
The myocardial extracellular matrix (ECM) is an intricate and dynamic network consisting of extracellular proteins that provides structural and functional support for the myocar‐ dium (1)
By measuring the levels of cardiac injury biomarkers in the serum samples, it was revealed that the ISO model group exhibited significantly increased levels of lactate dehydrogenase (LDH), α‐hydroxybutyrate dehydrogenase (α‐HBDH), creatine kinase isoenzyme MB (CK‐MB), cardiac troponin I (cTnI) and cardiac troponin T (cTnT) compared with those in the control group, whereas LQ treat‐ ment significantly suppressed the levels of these proteins at all doses tested (Fig. 1B‐F)
These results suggested that LQ treatment attenuated ISO‐induced cardiomyocyte damage and myocardial fibrosis
Summary
The myocardial extracellular matrix (ECM) is an intricate and dynamic network consisting of extracellular proteins that provides structural and functional support for the myocar‐ dium (1). The disruption of ECM homeostasis is a primary driver for the development of cardiac dysfunction and heart failure (2). The myocardial architecture is disorganized during myocardial fibrosis, which facilitates the progression of cardiac dysfunction, myocardial infarc‐ tion, ventricular arrhythmias and eventually heart failure (4). An effective and safe therapy that can inhibit myocardial fibrosis from progressing is critical to prevent heart failure in patients with cardiac diseases (5). The protein kinase B (AKT)/extracellular signal‐regulated kinase (ERK) signaling pathway is downstream of TGF‐β1 and can be activated during cardiac fibrosis (8). TGF‐β1 has been reported to trigger phosphorylation of the AKT pathway in a RhoA‐dependent manner, whereas it induces the activation of ERK via small GTPase or direct phosphorylation of the ShcA protein (9). As no efficient anti‐fibrotic treatment is currently available, the exploration of novel therapeutic approaches targeting these
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
