Department of Cardiology, Cardiovascular Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Medical Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Rev Physiol Biochem Pharmacol. 2020;178:83-110. doi: 10.1007/112_2020_42.
Elevated levels of plasma cholesterol, impaired vascular wall, and presence of inflammatory macrophages are important atherogenic risk factors contributing to atherosclerotic plaque formation and progression. The interventions modulating these risk factors have been found to protect against atherosclerosis development and to decrease atherosclerosis-related cardiovascular disorders. Nutritional approaches involving supplements followed by improving dietary habits and lifestyle have become growingly attractive and acceptable methods used to control atherosclerosis risk factors, mainly high levels of plasma cholesterol. There are a large number of studies that show berberine, a plant bioactive compound, could ameliorate atherosclerosis-related risk factors. In the present literature review, we put together this studies and provide integrated evidence that exhibits berberine has the potential atheroprotective effect through reducing increased levels of plasma cholesterol, particularly low-density lipoprotein (LDL) cholesterol (LDL-C) via LDL receptor (LDLR)-dependent and LDL receptor-independent mechanisms, inhibiting migration and inflammatory activity of macrophages, improving the functionality of endothelial cells via anti-oxidant activities, and suppressing proliferation of vascular smooth muscle cells. In conclusion, berberine can exert inhibitory effects on the atherosclerotic plaque development mainly through LDL-lowering activity and suppressing atherogenic functions of mentioned cells. As the second achievement of this review, among the signaling pathways through which berberine regulates intracellular processes, AMP-activated protein kinase (AMPK) has a central and critical role, showing that enhancing activity of AMPK pathway can be considered as a promising therapeutic approach for atherosclerosis treatment.
血浆胆固醇水平升高、血管壁受损以及炎症性巨噬细胞的存在是导致动脉粥样硬化斑块形成和进展的重要动脉粥样硬化危险因子。调节这些危险因子的干预措施已被发现可预防动脉粥样硬化的发展并降低与动脉粥样硬化相关的心血管疾病。涉及补充剂的营养方法，然后改善饮食习惯和生活方式，已成为越来越有吸引力和可接受的控制动脉粥样硬化危险因子的方法，主要是降低血浆胆固醇水平。有大量研究表明，植物生物活性化合物小檗碱可改善与动脉粥样硬化相关的危险因子。在本文献综述中，我们汇集了这些研究，并提供了综合证据，表明小檗碱具有通过降低升高的血浆胆固醇水平，特别是通过 LDL 受体（LDLR）依赖性和 LDLR 非依赖性机制降低 LDL 胆固醇（LDL-C），抑制巨噬细胞的迁移和炎症活性，通过抗氧化活性改善内皮细胞的功能以及抑制血管平滑肌细胞增殖，从而发挥抗动脉粥样硬化作用。总之，小檗碱主要通过降低 LDL 活性和抑制上述细胞的动脉粥样硬化功能来抑制动脉粥样硬化斑块的发展。作为本综述的第二个成果，在小檗碱调节细胞内过程的信号通路中，AMP 激活的蛋白激酶（AMPK）具有中心和关键作用，表明增强 AMPK 通路的活性可被视为治疗动脉粥样硬化的有前途的治疗方法。
