Yamagishi Sho-Ichi, Matsui Takanori, Ishibashi Yuji, Isami Fumiyuki, Abe Yumi, Sakaguchi Tatsuya, Higashimoto Yuichiro
Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Morinda Worldwide Inc., Tokyo 160- 0023, Japan.
Curr Pharm Des. 2017;23(8):1135-1141. doi: 10.2174/1381612822666161021155502.
Reducing sugars can react non-enzymatically with amino groups of proteins and lipids to form irreversibly cross-linked macroprotein derivatives called as advanced glycation end products (AGEs). Cross-linking modification of extracellular matrix proteins by AGEs deteriorate their tertiary structural integrity and function, contributing to aging-related organ damage and diabetes-associated complications, such as cardiovascular disease (CVD). Moreover, engagement of receptor for AGEs, RAGE with the ligands evoke oxidative stress generation and inflammatory, thrombotic and fibrotic reactions in various kinds of tissues, further exacerbating the deleterious effects of AGEs on multiple organ systems. So the AGE-RAGE axis is a novel therapeutic target for numerous devastating disorders. Several observational studies have shown the association of dietary consumption of fruits and vegetables with the reduced risk of CVD in a general population. Although beneficial effects of fruits and vegetables against CVD could mainly be ascribed to its anti-oxidative properties, blockade of the AGERAGE axis by phytochemicals may also contribute to cardiovascular event protection. Therefore, in this review, we focus on 4 phytochemicals (quercetin, sulforaphane, iridoids, and curcumin) and summarize their effects on AGE formation as well as RAGE-mediated signaling pathway in various cell types and organs, including endothelial cells, vessels, and heart.
还原糖可与蛋白质和脂质的氨基发生非酶反应,形成不可逆交联的大蛋白衍生物,称为晚期糖基化终末产物(AGEs)。AGEs对细胞外基质蛋白的交联修饰会破坏其三级结构完整性和功能,导致与衰老相关的器官损伤以及糖尿病相关并发症,如心血管疾病(CVD)。此外,AGEs受体(RAGE)与配体结合会在各种组织中引发氧化应激、炎症、血栓形成和纤维化反应,进一步加剧AGEs对多个器官系统的有害影响。因此,AGE-RAGE轴是众多毁灭性疾病的一个新的治疗靶点。几项观察性研究表明,在普通人群中,食用水果和蔬菜与降低CVD风险有关。尽管水果和蔬菜对CVD的有益作用主要归因于其抗氧化特性,但植物化学物质对AGE-RAGE轴的阻断作用也可能有助于预防心血管事件。因此,在本综述中,我们重点关注4种植物化学物质(槲皮素、萝卜硫素、环烯醚萜和姜黄素),并总结它们在包括内皮细胞、血管和心脏在内的各种细胞类型和器官中对AGE形成以及RAGE介导的信号通路的影响。