本文系Food Science and Human Wellness原创编译,欢迎分享,转载请授权。
根据世界卫生组织(WHO)报告,2019年约有1790万人死于心血管疾病(CVD),在过去10年内以增长率约为18.7%不断加剧。动脉粥样硬化或冠状动脉疾病(CAD)是最常见心血管疾病的表现症状,迄今已有约1.7%的世界人口(约1.26亿人)被诊断为心血管相关疾病,导致全球有近900万人口死于心血管相关疾病,1.64亿人因此遭受伤残生活。作为一种长期积累的慢性疾病,动脉粥样硬化主要表现为促动脉粥样硬化脂蛋白(例如氧化低密度脂蛋白(ox-LDL)在血管壁中积累、大动脉持续炎症、血管内壁的内皮细胞(ECs)和血管平滑肌细胞(VSMC)发生功能障碍,最终导致血管斑块的形成。一方面,不断生长的斑块会增加动脉的厚度和硬度,从而减少管腔内的血流量,并影响重要器官和组织的氧气输送。另一方面,不稳定斑块的突然破裂可导致心肌梗死(MI)、中风和心力衰竭(图1)。
目前,动脉粥样硬化临床最常见的预防方法是改变生活方式和药物治疗。在现有的治疗方法中,最广泛使用和有效的药物是他汀类药物(HMG-CoA还原酶抑制剂),主要通过降脂和抗炎,以及调节ECs凋亡的作用机制。然而,长期使用他汀类药物会产生严重的副作用,如胃肠道刺激、肝损伤和肌肉毒性,促使人们寻找预防和治疗动脉粥样硬化的替代策略。越来越多的研究指出,功能性食品、膳食补充剂和生物活性化合物(如多酚、类胡萝卜素、omega-3 脂肪酸、植物甾醇等)具有干预动脉粥样硬化斑块发展的潜力。已有大量相关动物实验报道,来自植物的天然酚类抗氧化剂,例如EGCG、白藜芦醇和槲皮素,具有动脉粥样硬化保护作用。叶黄素类(xanthophylls)是一类广泛存在于自然界中类胡萝卜素的一个主要类别。研究表明叶黄素具有抗氧化和抗炎特性,以及改善脂质代谢和内皮细胞功能的潜力,可作为一种辅助疗法预防和减缓动脉粥样硬化。
叶黄素类是指由具有共轭双键的烃组成的类胡萝卜素的氧化衍生物,其含氧基团包括羟基、甲氧基、羰基或环氧基团。这些官能团可影响其在消化过程中的吸收、代谢、分布和摄取。叶黄素类主要包括叶黄素(lutein)和玉米黄素(zeaxanthin)、β-隐黄素(β-cryptoxanthin)、虾青素(astaxanthin)和藻褐素(fucoxanthin)。正常饮食时,人体循环系统中可检测到叶黄素、玉米黄素和β-隐黄素。绿叶蔬菜和玉米是叶黄素和玉米黄素的良好来源,而β-隐黄素主要存在于辣椒、南瓜和木瓜中。作为结构异构体,叶黄素((3R,3'R,6'R)-β,e-胡萝卜素-3-3'-二醇)和玉米黄素((3R,3'R)-β,β-胡萝卜素的混合物)-3,3'二醇和(3R,3'S-内消旋)-β,β-胡萝卜素-3,3'-二醇)在其共轭链的每一端含有40个碳原子和两个羟基。与叶黄素相比,β-隐黄素(C40H56O)在其β-环上有一个源自β-胡萝卜素的单羟基。因此,β-隐黄素往往表现出比β-胡萝卜素更高的生物利用度,是VA的优质来源。鲑鱼、贝壳、微藻和某些蘑菇中富含虾青素。其天然来源通常含有3,3′-二羟基-β,β-胡萝卜素-4,4′-二酮,分子式为C40H52O4,存在(3-R,3′-S)异构体。与其他类胡萝卜素(例如β-胡萝卜素)相比,虾青素中与多烯主链结合的两个末端羰基可以增强其抗氧化性能。藻褐素(C42H58O6)是一种海洋来源叶黄素,可在褐海藻等大型藻类中大量积累。其结构相对更复杂,具有独特的烯丙基键、5,6-单环氧基团和多个含氧官能团。
目前,针对叶黄素类干预动脉粥样硬化发病进程及其潜在机制,在临床应用之前和临床实验的数据鲜有系统综述。基于此,本文从不同的科学数据库进行了较全面的文献检索,对叶黄素类与动脉粥样硬化进程干预的相关性及其潜在机制提供了新思路和见解(图2)。
图2 造成动脉粥样硬化的危险因素以及叶黄素类干预动脉粥样硬化发展的潜在作用靶点
在本综述中,文献检索使用的科学数据库包括PubMed、ScienceDirect、Google Scholar和Web of Science(文献发表时间从1990年1月到2022年9月)。搜索的主要关键词或相关词(例如PubMed中的MeSH术语),包括“xanthophyll”“carotenoid”“lutein”“zeaxanthin”“astaxanthin”“fucoxanthin”“β-cryptoxanthin”“atherosclerosis”“coronary artery disease”“anti-atherogenic”“cardio protection”和“cardio protectant”等。用于筛选涉及不同叶黄素类及其与动脉粥样硬化发病机制、预防和治疗相关的体外、体内、流行病学和人类干预等研究。
An overview of potential cardioprotective benefits of xanthophylls in atherosclerosis: an evidence-based review
Yuting Sua,b,c, Feng Chena,b, Jiehua Chena,b,*, Mingfu Wanga,b,d,*
a Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Shenzhen 518060, China
b Institution for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, China
c College of Civil and Transportation Engineering, Shenzhen University, Shenzhen 518060, China
d Shenzhen Key Laboratory of Food Nutrition and Health, Shenzhen University, Shenzhen 518060, China
*Corresponding author.
Abstract
Atherosclerosis, as the most prevalent form of cardiovascular disease, is characterized by oxidized lowdensity lipoprotein (ox-LDL) accumulation in the vascular wall, increased inflammation of the large arteries, dysfunction of the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), which may eventually lead to the formation of plaques. Xanthophylls, one of the main groups of carotenoids, have been proposed as preventive agents or adjunct therapies to prevent and slow the progression of atherosclerosis due to their cardioprotective properties. However, the underlying preventive mechanism of action of xanthophylls on the pathogenesis of atherosclerosis remains unclear, and clinical evidence of the effect of xanthophylls on atherosclerosis have not yet been summarized and critically reviewed. In this regard, we conducted a comprehensive literature search in four scientific databases (PubMed, Google Scholar, ScienceDirect and Web of Science) and carefully analyzed the existing evidence to provide meaningful insights on the association between xanthophylls and atherosclerosis from various aspects. Based on the evidence from in vitro and in vivo studies, we explored several potential mechanisms, including antioxidant effect, anti-inflammatory effect, regulation of lipid metabolism, and modulation of ECs and VSMCs dysfunction, and we found that a clear picture of regulatory pathways of xanthophylls on atherosclerosis prevention and treatment is still lacking. In addition, epidemiological studies suggested the possible relationship among high dietary intake of xanthophylls, high plasma/serum xanthophylls and a reduced risk of atherosclerosis. Direct evidence from interventional studies investigating the effect of xanthophylls on atherosclerosis is very sparse, whilst indirect clinical evidence was only limited to astaxanthin and lutein. Therefore, well-designed long-term randomized controlled trials (RCTs) are highly recommended for future studies to investigate the effective dose of different xanthophylls on atherosclerosis prevention and their possible ancillary effect in conjunction with drug therapies on different stages of atherosclerosis.
SU Y T, CHEN F, CHEN J H, et al. An overview of potential cardioprotective benefits of xanthophylls in atherosclerosis: an evidence-based review[J]. Food Science and Human Wellness, 2024, 13(4): 1739-1755. DOI:10.26599/FSHW.2022.9250147.
或点击下方阅读原文查看文章
为进一步促进动物源食品科学的发展,带动产业的技术创新,更好的保障人类身体健康和提高生活品质,北京食品科学研究院和中国食品杂志社将与陕西师范大学、新疆农业大学、浙江海洋大学、甘肃农业大学、大连民族大学、西北大学于2024年10月14-15日在陕西西安共同举办“2024年动物源食品科学与人类健康国际研讨会”。
长按二维码关注我们!