Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia, P.O.B. # 21, 121609 Moscow, Russia.
Curr Pharm Des. 2013;19(33):5909-28. doi: 10.2174/1381612811319330011.
The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.
大量他汀类药物和其他药物的临床试验结果表明,药物治疗在动脉粥样硬化的预防和消退方面具有主要可能性。本综述描述了使用培养的人动脉细胞进行大规模筛选抗动脉粥样硬化物质、研究导致其动脉粥样硬化相关作用的机制以及优化抗动脉粥样硬化和抗动脉粥样形成药物和饮食疗法的应用。天然产物可被视为有前途的抗动脉粥样硬化治疗药物。我们的基础研究表明,细胞脂质沉积是动脉粥样硬化病变发生的主要事件。我们使用细胞模型和天然产物开发了一种预防动脉细胞脂质积累的方法。基于我们对动脉粥样硬化的认识,我们开发了具有直接抗动脉粥样硬化活性的药物。为期两年的大蒜素(大蒜粉)治疗对无症状男性的颈动脉粥样硬化有直接的抗动脉粥样硬化作用。具有抗细胞因子活性的 Inflaminat(金盏花、接骨木、紫罗兰)在对无症状男性进行一年治疗后,显示出可使颈动脉粥样硬化消退。富含植物雌激素的药物卡尼纳特(大蒜粉、葡萄籽提取物、绿茶提取物、啤酒花提取物、β-胡萝卜素、α-生育酚和抗坏血酸)可预防绝经后妇女发生颈动脉粥样硬化。因此,我们的基础发现成功转化为临床实践。由于这种转化,开发了一种新的抗动脉粥样硬化治疗方法。我们的临床试验证实了这种新方法和新药的疗效。