title: Apigenin ameliorates hypertension-induced cardiac hypertrophy and down-regulates cardiac hypoxia inducible factor-lα in rats.
abstract: Apigenin is a natural flavonoid compound that can inhibit hypoxia-inducible factor (HIF)-1α expression in cultured tumor cells under hypoxic conditions. Hypertension-induced cardiac hypertrophy is always accompanied by abnormal myocardial glucolipid metabolism due to an increase of HIF-1α. However, whether or not apigenin may ameliorate the cardiac hypertrophy and abnormal myocardial glucolipid metabolism remains unknown. This study aimed to examine the effects of apigenin. Rats with cardiac hypertrophy induced by renovascular hypertension were treated with apigenin 50-100 mg kg(-1) (the doses can be achieved by pharmacological or dietary supplementation for an adult person) by gavage for 4 weeks. The results showed that after treatment with apigenin, the blood pressure, heart weight, heart weight index, cardiomyocyte cross-sectional area, serum angiotensin II, and serum and myocardial free fatty acids were reduced. It is important to note that apigenin decreased the expression level of myocardial HIF-1α protein. Moreover, apigenin simultaneously increased the expression levels of myocardial peroxisome proliferator-activated receptor (PPAR) α, carnitine palmitoyltransferase (CPT)-1, and pyruvate dehydrogenase kinase (PDK)-4 proteins and decreased the expression levels of myocardial PPARγ, glycerol-3-phosphate acyltransferase genes (GPAT), and glucose transporter (GLUT)-4 proteins. These findings demonstrated that apigenin could improve hypertensive cardiac hypertrophy and abnormal myocardial glucolipid metabolism in rats, and its mechanisms might be associated with the down-regulation of myocardial HIF-1α expression and, subsequently increasing the expressions of myocardial PPARα and its target genes CPT-1 and PDK-4, and decreasing the expressions of myocardial PPARγ and its target genes GPAT and GLUT-4.
authors.affiliation: Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China. xiemeilin@suda.edu.cn and Department of Pharmacy, The Affiliated Children's Hospital of Soochow University, Suzhou 215003, Jiangsu Province, China.
authors.forename: Zeng-Yan
authors.initials: ZY
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China. xiemeilin@suda.edu.cn.
authors.forename: Tian
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, The Affiliated Children's Hospital of Soochow University, Suzhou 215003, Jiangsu Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China. xiemeilin@suda.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China. xiemeilin@suda.edu.cn.
authors.forename: Mei-Lin
authors.initials: ML
authors.lastname: Xie
mesh_terms: D000818:Animals; D047310:Apigenin / Q000008:administration & dosage*; D006332:Cardiomegaly / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051275:Glucose Transporter Type 4; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047493:PPAR alpha; D047310:Apigenin; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4