Nepal Saroj, Malik Salma, Sharma Ashok Kumar, Bharti Saurabh, Kumar Narender, Siddiqui Khalid Mehmood, Bhatia Jagriti, Kumari Santosh, Arya Dharamvir Singh
Cardiovascular and Diabetes Research Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India.
Exp Toxicol Pathol. 2012 Nov;64(7-8):705-12. doi: 10.1016/j.etp.2011.01.003. Epub 2011 Feb 1.
This study was aimed to investigate whether standardized hydroalcoholic extract of abresham (AB) ameliorates dyslipidemia, hepatic steatosis and associated hypertension in rats fed with high-cholesterol/high-fat diet (HFD). HFD (55% calorie from fat and 2% cholesterol) were fed for 45 days to induce dyslipidemia, hepatic steatosis and associated hypertension. After confirmation of hypercholesterolemia (total cholesterol >150 mg/dl) on 30th day, different doses of AB (200-800 mg/kg/day) were administered for next 15 days. HFD administration for 45 days led to cardiometabolic syndrome characterized by significant increase in body weight, total cholesterol, triglyceride, low density lipoprotein cholesterol, TNF-α levels along with decrease in high density lipoprotein cholesterol and serum NO level. Furthermore, HFD resulted in significant increase in systolic arterial pressure, diastolic arterial pressure and mean arterial pressure. In addition, morphological studies revealed hepatic steatosis along with swelling of mitochondria and loss of cristae in hepatocyte and periarteritis in aorta. Treatment with AB for 15 days positively modulated the altered parameters in dose-dependent fashion, though maximum effect was seen at 800 mg/kg. These findings suggest that AB guard against cardiometabolic syndrome in HFD fed rats. It attenuates dyslipidemia, hepatic steatosis and associated hypertension by decreasing oxidative stress, TNF-α and normalizing NO production.
本研究旨在调查阿卜莱沙姆(AB)的标准化水醇提取物是否能改善喂食高胆固醇/高脂肪饮食(HFD)大鼠的血脂异常、肝脂肪变性及相关高血压。给予HFD(脂肪提供55%的热量,胆固醇含量为2%)45天以诱导血脂异常、肝脂肪变性及相关高血压。在第30天确认高胆固醇血症(总胆固醇>150mg/dl)后,接下来的15天给予不同剂量的AB(200 - 800mg/kg/天)。给予HFD 45天导致出现心脏代谢综合征,其特征为体重、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、TNF-α水平显著升高,同时高密度脂蛋白胆固醇和血清NO水平降低。此外,HFD导致收缩压、舒张压和平均动脉压显著升高。另外,形态学研究显示肝脂肪变性,同时肝细胞线粒体肿胀、嵴丢失以及主动脉动脉周围炎。用AB治疗15天以剂量依赖方式对改变的参数产生积极调节作用,尽管在800mg/kg时观察到最大效果。这些发现表明AB可预防喂食HFD大鼠的心脏代谢综合征。它通过降低氧化应激、TNF-α并使NO生成正常化来减轻血脂异常、肝脂肪变性及相关高血压。