Daisy Leaf Gentian Antagonism Protects against Adriamycin-induced Heart Failure in Mice

Abstract

Abstract Objective: This study aimed to evaluate the protective effect and underlying mechanisms of daisy leaf gentian, also known as bellidifolin (BEL), against heart injury in mice. Methods: Mice were randomly divided into four groups: Control, ADM (ADM alone), ADM+BEL (ADM plus daisy leaf gentian ketone monomer), and ADM+CAP (ADM plus captopril). We sacrificed mice using cervical dislocation.Heart structure and function were evaluated using echocardiography and hemodynamic testing. The serum levels of creatine kinase,aspartate aminotransferase, lactate dehydrogenase, and brain natriuretic peptide were measured using enzyme-linked immunosorbent assays. Hematoxylin and eosin staining and Masson’s staining were used to detect myocardial pathological changes. TUNEL staining and electron microscopy were used to detect cardiomyocyte apoptosis. Transmission electron microscopy was used to observe ultrastructural changes in the cardiomyocyte nuclei and mitochondria.Immunohistochemical analysis,Western blot and real-time PCR assays were used to measure protein expression and mRNA levels of myocardial factors. Results: ADM induced chronic heart failure in mice, and BEL improved the heart function in ADM-treated mice. Cardiomyocyte apoptosis was significantly increased in the ADM group, but apoptosis in the ADM+BEL and ADM+CAP groups was significantly reduced compared with the model animals. mRNA levels and protein expression of 78-kD glucose-regulated protein,brain natriuretic peptide,caspase-12, and phosphorylated eukaryotic cell translation initiation factor 2α were significantly higher in the ADM group. BEL or CAP successfully suppressed ADM-induced upregulation of these genes. Conclusions: Daisy leaf gentian improved heart function and reduced cardiomyocyte apoptosis in mice following ADM-induced heart failure. The cardioprotective effect of daisy leaf gentian may be related to endoplasmic reticulum stress.