Abstract. Cardiac remodeling is a major determinant of heart failure characterized by cardiac hypertrophy and fibrosis. Sanguinarine exerts widespread pharmacological effects, including antitumor and anti-inflammatory responses. In the present study, the effect of sanguinarine on cardiac hypertrophy, fibrosis and heart function was determined using the model induced by aortic banding (AB) in mice. AB surgery and sham surgery were performed on male wild-type C57 mice, aged 8-10 weeks, with or without administration of sanguinarine from one week after surgery for an additional seven weeks. Sanguinarine protected against the cardiac hypertrophy, fibrosis and dysfunction induced by AB, as assessed by the heart weight/body weight, lung weight/body weight and heart weight/tibia length ratios, echocardiographic and hemodynamic parameters, histological analysis, and the gene expression levels of hypertrophic and fibrotic markers. The inhibitory effect of sanguinarine on cardiac remodeling was mediated by inhibiting nuclear factor (NF)-κB signaling pathway activation. The findings indicated that sanguinarine protected against cardiac hypertrophy and fibrosis via inhibiting NF-κB activation. These findings may be used to develop a potential therapeutic drug for treating cardiac remodeling and heart failure.
IntroductionHeart failure (HF) is a major health and economic burden worldwide, and its prevalence is continuously increasing (1). The key pathophysiological process that ultimately results in heart failure is cardiac remodeling in response to chronic pathological stresses, such as hypertension and myocardial ischemia (2). Cardiac remodeling, which involves myocyte hypertrophy along with interstitial cell proliferation and extracellular matrix remodeling, induces structural and functional changes, mainly in the left ventricle (3). Initially, cardiac remodeling is a beneficial compensatory process, which reduces cardiac wall stress and increases cardiac output, but remodeling ultimately results in the inability of the heart to meet hemodynamic demands. Despite a number of important therapeutic advances in the treatment of symptomatic HF, the prevalence, mortality and cost associated with HF continue to increase (4). Therefore, the development of novel therapeutic strategies to attenuate cardiac remodeling and prevent heart failure is an urgent goal for the biomedical community.Sanguinarine, derived from the root of Sanguinaria canadensis and other poppy fumaria species, has been demonstrated to exert widespread pharmacological actions, including antimicrobial, antitumor and anti-inflammatory responses (5-8). In particular, sanguinarine was reported to possess cardioprotective outcomes, such as antihypertension, antiplatelet and positive inotropic effects (9). However, the influence of sanguinarine on cardiac remodeling was unknown.The aim of the present study was to investigate whether sanguinarine improved cardiac hypertrophy and fibrosis in mice.
Materials and methodsMaterials and animal models. Sanguinarine (>98%) wa...