Oleuropein: a narrative review on its role in neurodegenerative diseases

Riquelme, Constanza V.; Pando, María E.*

Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile

*Correspondence to: María E. Pando, PhD, pandosanmartin@uchile.cl.

Abstract

Olive oil, a cornerstone of the Mediterranean diet, contains trace amounts of oleuropein, a polyphenolic compound and its active metabolite hydroxytyrosol, which exhibit significant neuroprotective effects by reducing oxidative stress and brain inflammation. These properties make them promising for managing neurodegenerative diseases such as Alzheimer’s disease. This review synthesizes the current literature on the chemistry, biosynthesis, and neuroprotective activities of oleuropein and hydroxytyrosol, emphasizing their antioxidant and anti-inflammatory effects. Research indicates that hydroxytyrosol is bioavailable and rapidly distributed throughout the body, including brain tissue, due to its ability to cross the blood-brain barrier. In contrast, oleuropein requires metabolic conversion for bioavailability. Both compounds have been shown in preclinical animal studies to mitigate oxidative stress, promote autophagy, and facilitate the clearance of amyloid-beta aggregates. Moreover, they have been found to alleviate mitochondrial damage and dysfunction, which are critical factors in neurodegeneration. In animal and human studies, oleuropein and hydroxytyrosol have improved cognitive function, reduced neuroinflammation, and improved overall brain health. The mechanisms underlying these effects include the restoration of redox balance and the modulation of inflammatory pathways in the aging brain. Despite these promising findings, human clinical trials are needed to assess the long-term safety and efficacy of oleuropein and hydroxytyrosol in clinical settings. Understanding their role in neuroprotection could lead to effective interventions for preventing or slowing cognitive decline associated with aging and neurodegenerative diseases. Overall, oleuropein and hydroxytyrosol represent a compelling area of study within the realm of antioxidants and their application in neuroprotection.

橄榄苦苷在神经退行性疾病中的作用：叙述性综述

摘要

橄榄油是地中海饮食的基石，含有微量的多酚化合物橄榄苦苷（OLE），其活性代谢产物羟基酪醇（HT）通过减少氧化应激和脑部炎症表现出显著的神经保护作用。这些特性使它们在治疗阿尔茨海默病等神经退行性疾病方面大有可为。文章综述了目前有关橄榄苦苷和羟基酪醇的化学、生物合成和神经保护活性的文献，强调了它们的抗氧化和抗炎作用。研究表明，由于羟基酪醇能够穿过血脑屏障，因此在人体内（包括脑组织）可被生物利用并迅速分布。与此相反，橄榄苦苷需要经过新陈代谢转化才能获得生物利用度。临床前研究表明，橄榄苦苷和羟基酪醇都能减轻氧化应激，促进自噬，促进淀粉样蛋白-β聚集体的清除。此外，它们还能减轻线粒体损伤和功能障碍，而线粒体损伤和功能障碍是导致神经退行性变的关键因素。在动物和人体研究中，橄榄苦苷和羟基酪醇都能增强认知功能、减少神经炎症并改善大脑的整体健康。这些作用的机制包括恢复氧化还原平衡和调节老化大脑中的炎症通路。尽管这些研究结果很有希望，但仍需要进行人体临床试验，以评估橄榄苦苷和羟基酪醇在临床环境中的长期安全性和有效性。了解它们在神经保护中的作用，可以为预防或减缓与衰老和神经退行性疾病相关的认知能力下降提供有效的干预措施。总之，橄榄苦苷和羟基酪醇是抗氧化剂及其在神经保护中应用的一个引人注目的研究领域。