Chrysanthemum morifolium extract improves hypertension-induced cardiac hypertrophy in rats by reduction of blood pressure and inhibition of myocardial hypoxia inducible factor-1alpha expression

Context: Chrysanthemum morifolium Ramat. (Asteraceae) extract (CME) possesses a vasodilator effect in vitro. However, the use of polyphenol-rich CME in the treatment of hypertension-induced cardiac hypertrophy has not been reported. Objective: We investigated the effect of polyphenol-rich CME on hypertension-induced cardiac hypertrophy in rats and its possible mechanism of action. Materials and methods: The Sprague-Dawley rat model with cardiac hypertrophy was induced by renovascular hypertension. The blood pressure, cardiac weight index, free fatty acids (FFA) in serum and myocardium, and protein expressions of myocardial hypoxia inducible factor-1 alpha (HIF-1 alpha), peroxisome proliferator-activated receptor alpha (PPAR alpha), carnitine palmitoyltransferase-1a (CPT-1a), pyruvate dehydrogenase kinase-4 (PDK-4) and glucose transporter-4 (GLUT-4) were measured after treating hypertensive rats with polyphenol-rich CME of anthodia 75-150 mg/kg once daily for 4 weeks. A myocardial histological examination was also conducted. Results: After CME treatment, the blood pressure, cardiac weight and cardiac weight index decreased by 5.7-9.6%, 9.2-18.4% and 10.9-20.1%, respectively, and the cardiomyocyte cross-sectional area also decreased by 8.3-30.4%. The CME treatment simultaneously decreased the FFA in serum and myocardium and protein expressions of myocardial HIF-1 alpha and GLUT-4, and increased the protein expressions of myocardial PPAR alpha, CPT-1a and PDK-4, especially in the CME 150 mg/kg group (p<0.05 or p<0.01). Discussion and conclusion: Polyphenol-rich CME may alleviate hypertensive cardiac hypertrophy in rats. Its mechanisms may be related to the reduction of blood pressure and amelioration of the myocardial energy metabolism. The latter may be attributed to the inhibition of HIF-1 alpha expression and subsequent modulation of PPAR alpha-mediated CPT-1a, PDK-4 and GLUT-4 expressions.