Laboratory of Food & Health, Research Group on Quality, Safety, and Bioactivity of Plant Foods, Campus de Espinardo, CEBAS-CSIC, 30100 Murcia, Spain.
Instituto de Biologia Experimental e Tecnológica (iBET), Apartado 12, 2781-901 Oeiras, Portugal.
Nutrients. 2022 Sep 2;14(17):3632. doi: 10.3390/nu14173632.
Exosomes are extracellular vesicles (EVs) that regulate intercellular signaling by transferring small RNAs, proteins, nucleic acids, lipids, and other metabolites to local or distant organs, including the brain, by crossing the blood-brain barrier. However, the transport of (poly)phenols in human EVs has not yet been described. Therefore, we aimed here to explore (i) whether resveratrol and (or) its derived metabolites are found in the cargo of human plasma exosome-containing EVs (E-EVs), (ii) when this incorporation occurs, and (iii) whether resveratrol intake stimulates the release of E-EVs. Thus, in a pharmacokinetic study, healthy volunteers (n = 16) consumed 1 capsule (420 mg resveratrol) in the evening before attending the clinic and one more capsule on the day of the pharmacokinetics. The plasma and the isolated E-EVs were analyzed using UPLC-ESI-QTOF-MS. Of 17 metabolites in the plasma, 9 were identified in the E-EVs, but not free resveratrol. The kinetic profiles of resveratrol metabolites were similar in the plasma and the E-EVs, a higher metabolite concentration being detected in the plasma than in the E-EVs. However, the plasma/E-EVs ratio decreased in the gut microbial metabolites, suggesting their better encapsulation efficiency in E-EVs. In addition, glucuronide conjugates of resveratrol, dihydroresveratrol, and lunularin were incorporated into the E-EVs more efficiently than their corresponding sulfates despite glucuronides reaching lower plasma concentrations. Notably, more E-EVs were detected 10 h after resveratrol consumption. This exploratory study provides the first evidence that (i) resveratrol metabolites are transported by E-EVs, with a preference for glucuronide vs. sulfates, (ii) the gut microbial metabolites concentration and kinetic profiles are closely similar in E-EVs and plasma, and (iii) resveratrol intake elicits E-EVs secretion. Overall, these results open new research avenues on the possible role of E-EVs in (poly)phenol health effects.
外泌体是细胞外囊泡 (EVs)，通过跨越血脑屏障将小 RNA、蛋白质、核酸、脂质和其他代谢物等转移到局部或远处器官，从而调节细胞间信号转导。然而，人类 EV 中的（多）酚类物质的转运尚未被描述。因此，我们旨在探讨：(i) 是否有白藜芦醇及其衍生代谢物存在于含人类血浆外泌体的 EV（E-EV）的货物中，(ii) 这种结合发生的时间，以及 (iii) 白藜芦醇的摄入是否会刺激 E-EV 的释放。因此，在一项药代动力学研究中，健康志愿者（n=16）在晚上服用 1 粒（420mg 白藜芦醇）胶囊，然后在药代动力学当天再服用 1 粒胶囊。使用 UPLC-ESI-QTOF-MS 分析血浆和分离的 E-EV。在血浆中的 17 种代谢物中，有 9 种在 E-EV 中被鉴定出来，但没有游离的白藜芦醇。白藜芦醇代谢物的动力学特征在血浆和 E-EV 中相似，在血浆中的代谢物浓度高于 E-EV 中的浓度。然而，在肠道微生物代谢物中，血浆/E-EV 的比值降低，这表明它们在 E-EV 中的包封效率更好。此外，白藜芦醇、二氢白藜芦醇和月见草素的葡萄糖醛酸轭合物比相应的硫酸盐更有效地被包裹在 E-EV 中，尽管葡萄糖醛酸轭合物的血浆浓度较低。值得注意的是，在白藜芦醇消耗后 10 小时检测到更多的 E-EV。这项探索性研究首次提供了证据，证明 (i) 白藜芦醇代谢物通过 E-EV 转运，葡萄糖醛酸轭合物比硫酸盐更有优势，(ii) 肠道微生物代谢物的浓度和动力学特征在 E-EV 和血浆中非常相似，以及 (iii) 白藜芦醇的摄入会引起 E-EV 的分泌。总的来说，这些结果为 E-EV 在（多）酚类物质健康效应中的可能作用开辟了新的研究途径。
