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


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-1α (HIF-1α), peroxisome proliferator-activated receptor α (PPARα), 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-1α and GLUT-4, and increased the protein expressions of myocardial PPARα, CPT-1a and PDK-4, especially in the CME 150 mg/kg group (p < 0.05 or p < 0.01).


CONCLUSIONS
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-1α expression and subsequent modulation of PPARα-mediated CPT-1a, PDK-4 and GLUT-4 expressions.
a Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases , College of Pharmaceutical Sciences, Soochow University , Suzhou , Jiangsu Province , P.R. China.
Tian
T
Gao
a Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases , College of Pharmaceutical Sciences, Soochow University , Suzhou , Jiangsu Province , P.R. China.|b Department of Pharmacy , the Affiliated Children's Hospital of Soochow University , Suzhou , Jiangsu Province , P.R. China.
Zeng-Yan
ZY
Zhu
a Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases , College of Pharmaceutical Sciences, Soochow University , Suzhou , Jiangsu Province , P.R. China.
Xiang
X
Zhou
a Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases , College of Pharmaceutical Sciences, Soochow University , Suzhou , Jiangsu Province , P.R. China.
Mei-Lin
ML
Xie
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D006332:Cardiomegaly / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D031202:Chrysanthemum; D035264:Flowers; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010936:Plant Extracts
Cardiac energy metabolism; carnitine palmitoyltransferase-1a; glucose transporter-4; peroxisome proliferator-activated receptor α; pyruvate dehydrogenase kinase-4