Zordoky Beshay N M, Robertson Ian M, Dyck Jason R B
Cardiovascular Research Centre, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Cardiovascular Research Centre, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Biochim Biophys Acta. 2015 Jun;1852(6):1155-77. doi: 10.1016/j.bbadis.2014.10.016. Epub 2014 Nov 1.
Cardiovascular disease is the leading cause of death worldwide. Despite advancements in diagnosis and treatment of cardiovascular disease, the incidence of cardiovascular disease is still rising. Therefore, new lines of medications are needed to treat the growing population of patients with cardiovascular disease. Although the majority of the existing pharmacotherapies for cardiovascular disease are synthesized molecules, natural compounds, such as resveratrol, are also being tested. Resveratrol is a non-flavonoid polyphenolic compound, which has several biological effects. Preclinical studies have provided convincing evidence that resveratrol has beneficial effects in animal models of hypertension, atherosclerosis, stroke, ischemic heart disease, arrhythmia, chemotherapy-induced cardiotoxicity, diabetic cardiomyopathy, and heart failure. Although not fully delineated, some of the beneficial cardiovascular effects of resveratrol are mediated through activation of silent information regulator 1 (SIRT1), AMP-activated protein kinase (AMPK), and endogenous anti-oxidant enzymes. In addition to these pathways, the anti-inflammatory, anti-platelet, insulin-sensitizing, and lipid-lowering properties of resveratrol contribute to its beneficial cardiovascular effects. Despite the promise of resveratrol as a treatment for numerous cardiovascular diseases, the clinical studies for resveratrol are still limited. In addition, several conflicting results from trials have been reported, which demonstrates the challenges that face the translation of the exciting preclinical findings to humans. Herein, we will review much of the preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular disease and provide information about the physiological and molecular signaling mechanisms involved. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.
心血管疾病是全球主要的死亡原因。尽管在心血管疾病的诊断和治疗方面取得了进展,但心血管疾病的发病率仍在上升。因此,需要新的药物系列来治疗不断增加的心血管疾病患者群体。虽然现有的大多数心血管疾病药物疗法都是合成分子,但天然化合物,如白藜芦醇,也正在接受测试。白藜芦醇是一种非黄酮类多酚化合物,具有多种生物学效应。临床前研究提供了令人信服的证据,表明白藜芦醇在高血压、动脉粥样硬化、中风、缺血性心脏病、心律失常、化疗引起的心脏毒性、糖尿病心肌病和心力衰竭的动物模型中具有有益作用。虽然尚未完全阐明,但白藜芦醇的一些有益心血管作用是通过激活沉默信息调节因子1(SIRT1)、AMP激活的蛋白激酶(AMPK)和内源性抗氧化酶介导的。除了这些途径外,白藜芦醇的抗炎、抗血小板、胰岛素增敏和降脂特性也有助于其有益的心血管作用。尽管白藜芦醇有望用于治疗多种心血管疾病,但其临床研究仍然有限。此外,已经报道了一些试验的相互矛盾的结果,这表明将令人兴奋的临床前研究结果转化为人类应用面临的挑战。在此,我们将回顾白藜芦醇在治疗心血管疾病中作用的许多临床前和临床证据,并提供有关所涉及的生理和分子信号机制的信息。本文是名为:白藜芦醇:将临床前研究结果转化为改善患者预后的挑战的特刊的一部分。