Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa (CSIC), Seville, Spain.
Department of Biochemistry and Molecular Pharmacology, Instituto de Parasitologia y Biomedicina (CSIC), Granada, Spain.
Food Funct. 2017 Aug 1;8(8):2905-2914. doi: 10.1039/c7fo00641a. Epub 2017 Jul 25.
Tyrosol (Tyr) is a phenolic compound found in virgin olive oil. After ingestion, Tyr undergoes extensive first pass intestinal/hepatic metabolism. However, knowledge about the biological effects of Tyr metabolites is scarce. We chemically synthesized Tyr glucuronate (Tyr-GLU) and sulphate (Tyr-SUL) metabolites and explored their properties against oxidative stress and inflammation in TNF-α-treated human umbilical vein endothelial cells (hECs). Tyr and Tyr-SUL prevented the rise of reactive oxygen species, the depletion of glutathione, and the down-regulation of glutathione peroxidase 1, glutamate-cysteine ligase catalytic subunit, and heme oxygenase-1 genes. Tyr-SUL and to a lower extent Tyr and Tyr-GLU prevented the phosphorylation of NF-κB signaling proteins. Tyr-GLU and Tyr-SUL also prevented the over-expression of adhesion molecules at gene, protein, and secretory levels, and the adhesion (Tyr-SUL > Tyr-GLU) of human monocytes to hECs. In vivo, Tyr, and most notably Tyr-SUL in a dose-dependent manner, ameliorated plantar and ear edemas in mice models of acute and chronic inflammation. This study demonstrates the antioxidant and/or anti-inflammatory properties of Tyr metabolites, with Tyr-SUL being the most effective.
酪醇（Tyr）是一种存在于特级初榨橄榄油中的酚类化合物。在摄入后，Tyr 会经历广泛的肠道/肝脏首过代谢。然而，关于 Tyr 代谢物的生物学效应的知识还很缺乏。我们化学合成了 Tyr 葡萄糖醛酸（Tyr-GLU）和硫酸盐（Tyr-SUL）代谢物，并探讨了它们在 TNF-α 处理的人脐静脉内皮细胞（hECs）中对抗氧化应激和炎症的特性。Tyr 和 Tyr-SUL 可防止活性氧的增加、谷胱甘肽的消耗以及谷胱甘肽过氧化物酶 1、谷氨酸-半胱氨酸连接酶催化亚基和血红素加氧酶-1 基因的下调。Tyr-SUL 和在较低程度上 Tyr 和 Tyr-GLU 可防止 NF-κB 信号蛋白的磷酸化。Tyr-GLU 和 Tyr-SUL 还可防止黏附分子在基因、蛋白质和分泌水平上的过度表达，以及人单核细胞与 hECs 的黏附（Tyr-SUL>Tyr-GLU）。在体内，Tyr，尤其是 Tyr-SUL，可依赖剂量地改善急性和慢性炎症小鼠模型中的足底和耳部水肿。本研究证明了 Tyr 代谢物的抗氧化和/或抗炎特性，其中 Tyr-SUL 的效果最为显著。
