Huang T H, He L, Qin Q, Yang Q, Peng G, Harada M, Qi Y, Yamahara J, Roufogalis B D, Li Y
Faculty of Pharmacy, University of Sydney, Australia.
Diabetes Obes Metab. 2008 Jul;10(7):574-85. doi: 10.1111/j.1463-1326.2007.00750.x. Epub 2007 Jul 21.
We investigated the effect of the water extract of Salacia oblonga (SOE), an ayurvedic antidiabetic and antiobesity medicine, on obesity and diabetes-associated cardiac hypertrophy and discuss the role of modulation of cardiac angiotensin II type 1 receptor (AT(1)) expression in the effect.
SOE (100 mg/kg) was given orally to male Zucker diabetic fatty (ZDF) rats for 7 weeks. At the end-point of the treatment, the hearts and left ventricles were weighed, cardiomyocyte cross-sectional areas were measured, and cardiac gene profiles were analysed. On the other hand, angiotensin II-stimulated embryonic rat heart-derived H9c2 cells and neonatal rat cardiac fibroblasts were pretreated with SOE and one of its prominent components mangiferin (MA), respectively. Atrial natriuretic peptide (ANP) mRNA expression and protein synthesis and [(3)H]thymidine incorporation were determined.
SOE-treated ZDF rats showed less cardiac hypertrophy (decrease in weights of the hearts and left ventricles and reduced cardiomyocyte cross-sectional areas). SOE treatment suppressed cardiac overexpression of ANP, brain natriuretic peptide (BNP) and AT(1) mRNAs and AT(1) protein in ZDF rats. SOE (50-100 microg/ml) and MA (25 micromol) suppressed angiotensin II-induced ANP mRNA overexpression and protein synthesis in H9c2 cells. They also inhibited angiotensin II-stimulated [(3)H]thymidine incorporation by cardiac fibroblasts.
Our findings demonstrate that SOE decreases cardiac hypertrophy in ZDF rats, at least in part by inhibiting cardiac AT(1) overexpression. These studies provide insights into a potential cardioprotective role of a traditional herb, which supports further clinical evaluation in obesity and diabetes-associated cardiac hypertrophy.
我们研究了印度传统抗糖尿病和抗肥胖药物长椭圆叶匙羹藤水提取物(SOE)对肥胖及糖尿病相关心脏肥大的影响,并探讨了心脏1型血管紧张素II受体(AT(1))表达调节在该效应中的作用。
给雄性Zucker糖尿病肥胖(ZDF)大鼠口服SOE(100毫克/千克),持续7周。在治疗终点,称量心脏和左心室重量,测量心肌细胞横截面积,并分析心脏基因谱。另一方面,分别用SOE及其主要成分之一芒果苷(MA)预处理血管紧张素II刺激的胚胎大鼠心脏来源的H9c2细胞和新生大鼠心脏成纤维细胞。测定心房利钠肽(ANP)mRNA表达、蛋白质合成及[³H]胸腺嘧啶掺入情况。
经SOE治疗的ZDF大鼠心脏肥大程度较轻(心脏和左心室重量减轻,心肌细胞横截面积减小)。SOE治疗抑制了ZDF大鼠心脏中ANP、脑利钠肽(BNP)和AT(1) mRNA的过度表达以及AT(1)蛋白的表达。SOE(50 - 100微克/毫升)和MA(25微摩尔)抑制了血管紧张素II诱导的H9c2细胞中ANP mRNA的过度表达和蛋白质合成。它们还抑制了血管紧张素II刺激的心脏成纤维细胞的[³H]胸腺嘧啶掺入。
我们的研究结果表明,SOE可减轻ZDF大鼠的心脏肥大,至少部分是通过抑制心脏AT(1)的过度表达实现的。这些研究为一种传统草药的潜在心脏保护作用提供了见解,支持在肥胖和糖尿病相关心脏肥大方面进行进一步的临床评估。