Anti-atherosclerotic therapy based on botanicals.

Alexander N Orekhov, Igor A Sobenin, Nikolay V Korneev, Tatyana V Kirichenko, Veronika A Myasoedova, Alexandra A Melnichenko, Mercedes Balcells, Elazer R Edelman, Yuri V Bobryshev
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Abstract

Natural products including botanicals for both therapy of clinical manifestations of atherosclerosis and reduction of atherosclerosis risk factors are topics of recent patents. Only a few recent patents are relevant to the direct antiatherosclerotic therapy leading to regression of atherosclerotic lesions. Earlier, using a cellular model we have developed and patented several anti-atherosclerotic drugs. The AMAR (Atherosclerosis Monitoring and Atherogenicity Reduction) study was designed to estimate the effect of two-year treatment with time-released garlic-based drug Allicor on the progression of carotid atherosclerosis in 196 asymptomatic men aged 40-74 in double-blinded placebo-controlled randomized clinical study. The primary outcome was the rate of atherosclerosis progression, measured by high-resolution B-mode ultrasonography as the increase in carotid intima-media thickness (IMT) of the far wall of common carotid arteries. The mean rate of IMT changes in Allicor-treated group (-0.022±0.007 mm per year) was significantly different (P = 0.002) from the placebo group in which there was a moderate progression of 0.015±0.008 mm at the overall mean baseline IMT of 0.931±0.009 mm. A significant correlation was found between the changes in blood serum atherogenicity (the ability of serum to induce cholesterol accumulation in cultured cells) during the study and the changes in intima-media thickness of common carotid arteries (r = 0.144, P = 0.045). Thus, the results of AMAR study demonstrate that long-term treatment with Allicor has a direct anti-atherosclerotic effect on carotid atherosclerosis and this effect is likely to be due to serum atherogenicity inhibition. The beneficial effects of other botanicals including Inflaminat (calendula, elder and violet), phytoestrogen- rich Karinat (garlic powder, extract of grape seeds, green tea leafs, hop cones, β-carotene, α-tocopherol and ascorbic acid) on atherosclerosis have also been revealed in clinical studies which enforces a view that botanicals might represent promising drugs for anti-atherosclerotic therapy.

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以植物药为基础的抗动脉粥样硬化疗法。
用于治疗动脉粥样硬化临床表现和减少动脉粥样硬化危险因素的天然产品(包括植物药)是近期专利的主题。只有少数近期专利与直接抗动脉粥样硬化治疗有关,从而导致动脉粥样硬化病变的消退。早些时候,我们利用细胞模型开发了几种抗动脉粥样硬化药物,并申请了专利。AMAR(动脉粥样硬化监测和减少动脉粥样硬化)研究旨在通过双盲安慰剂对照随机临床研究,估算使用大蒜类定时释放药物 Allicor 治疗两年对 196 名 40-74 岁无症状男性颈动脉粥样硬化进展的影响。研究的主要结果是动脉粥样硬化的进展速度,通过高分辨率 B 型超声波造影术测量,即颈总动脉远端壁的颈动脉内膜中层厚度(IMT)的增加。爱利可治疗组的 IMT 平均变化率(-0.022±0.007 毫米/年)与安慰剂组有显著差异(P = 0.002),安慰剂组的平均基线 IMT 为 0.931±0.009 毫米,而爱利可治疗组的平均基线 IMT 变化率为 0.015±0.008 毫米,属于中度进展。研究期间,血清致动脉粥样硬化性(血清诱导胆固醇在培养细胞中积累的能力)的变化与颈总动脉内膜厚度的变化之间存在明显的相关性(r = 0.144,P = 0.045)。因此,AMAR 研究结果表明,长期服用艾力可对颈动脉粥样硬化有直接的抗动脉粥样硬化作用,而这种作用很可能是由于抑制血清动脉粥样硬化所致。临床研究还发现了其他植物药对动脉粥样硬化的有益作用,包括 Inflaminat(金盏花、接骨木和紫罗兰)、富含植物雌激素的 Karinat(大蒜粉、葡萄籽提取物、绿茶叶、酒花球果、β-胡萝卜素、α-生育酚和抗坏血酸),这进一步证实了植物药可能是抗动脉粥样硬化治疗的有效药物。
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