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.
Department of Pharmacy, The Affiliated Children's Hospital of Soochow University, Suzhou 215003, Jiangsu Province, China.
Food Funct. 2016 Apr;7(4):1992-8. doi: 10.1039/c5fo01464f.
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.
芹菜素是一种天然黄酮类化合物，可在缺氧条件下抑制培养肿瘤细胞中缺氧诱导因子 (HIF)-1α 的表达。高血压引起的心脏肥大总是伴随着异常的心肌糖脂代谢，因为 HIF-1α 的增加。然而，芹菜素是否可以改善心脏肥大和异常的心肌糖脂代谢尚不清楚。本研究旨在研究芹菜素的作用。用芹菜素（灌胃 50-100mg/kg，这些剂量可以通过药理或饮食补充来达到一个成年人的剂量）治疗 4 周可减轻由肾血管性高血压引起的心脏肥大的大鼠。结果表明，用芹菜素治疗后，血压、心脏重量、心脏重量指数、心肌细胞横截面积、血清血管紧张素 II 和血清及心肌游离脂肪酸降低。重要的是，芹菜素降低了心肌 HIF-1α 蛋白的表达水平。此外，芹菜素同时增加了心肌过氧化物酶体增殖物激活受体 (PPAR)α、肉碱棕榈酰转移酶 (CPT)-1 和丙酮酸脱氢酶激酶 (PDK)-4 蛋白的表达水平，并降低了心肌 PPARγ、甘油-3-磷酸酰基转移酶基因 (GPAT) 和葡萄糖转运蛋白 (GLUT)-4 蛋白的表达水平。这些发现表明，芹菜素可改善高血压性心脏肥大和大鼠异常心肌糖脂代谢，其机制可能与下调心肌 HIF-1α 表达有关，随后增加心肌 PPARα 及其靶基因 CPT-1 和 PDK-4 的表达，并降低心肌 PPARγ 及其靶基因 GPAT 和 GLUT-4 的表达。
