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首页> 外文期刊>Journal of biochemical and molecular toxicology >Oligomeric proanthocyanidins mitigate cholesterol and cholic acid diet-induced hepatic dysfunction in male Sprague Dawley rats
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Oligomeric proanthocyanidins mitigate cholesterol and cholic acid diet-induced hepatic dysfunction in male Sprague Dawley rats

机译：低聚原花青素在雄性Sprague Dawley大鼠中减轻胆固醇和胆酸饮食诱导的肝功能障碍

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摘要

Dysregulated synthesis of hepatic cholesterol is a critical determinant of atherosclerosis. The combination of cholesterol and cholic acid (CC) diet supplementation to animal models is associated with hepatic dysfunction-mediated atherosclerosis. The current study was designed to investigate the hepatic cholesterol-lowering effects of oligomeric proanthocyanidins (OPC) in CC diet fed rats. CC diet-induced group exhibited significant increase in the hepatic lipid profile, activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR), PON-1, LCAT, LPL, and LPO levels, and messenger RNA expression of HMGR, low-density lipoprotein receptor (LDLr), and HNF-4 alpha. Administration of OPC (100 mg/kg/bwt) resulted in the significant reduction of lipid profile and HMGR levels, with concomitant increase in the levels of cholesterol-regulating enzymes and upregulated expression of LDLr and HNF-4 alpha, which was similar to atorvastatin. Molecular docking studies also revealed that proanthocyanidins had a strong binding affinity to HMGR, similar to atorvastatin. Our findings suggest that OPC regulate the impaired cholesterol metabolism-associated atherosclerosis through hepatic cholesterol-lowering effect.
机译：肝胆固醇的失调合成是动脉粥样硬化的关键决定因素。胆固醇和胆酸（CC）饮食补充到动物模型的组合与肝功能紊乱介导的动脉粥样硬化有关。目前的研究旨在探讨CC饮食中低聚原花青素（OPC）的肝胆固醇降低效果。 CC饮食诱导的组在肝脂谱的显着增加，3-羟基-3-甲基抑制酶A（HMG-COA）还原酶（HMG），PON-1，LCAT，LPL和LPO水平和信使RNA的活性HMGR，低密度脂蛋白受体（LDLR）和HNF-4α的表达。施用OPC（100mg / kg / bwt）导致脂质曲线和hmgr水平的显着降低，伴随胆固醇调节酶的水平和LDLR和HNF-4α的上调表达的增加，这与阿托伐他汀相似。分子对接研究还揭示了原花青素对HMGR具有强烈的结合亲和力，类似于阿托伐他汀。我们的研究结果表明，OPC通过肝胆胆固醇降低效应调节胆固醇代谢相关的动脉粥样硬化。

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