Department Bioresource Technology, Okinawa National College of Technology, 905 Henoko, Nago-city, Okinawa Prefecture 905-2192, Japan.
Mar Drugs. 2017 Oct 6;15(10):305. doi: 10.3390/md15100305.
In this study, the function of fucoxanthinol (FxOH) as a bioavailable marine carotenoid together with the pre-metabolite, fucoxanthin (Fx), was examined through the Nrf2-ARE pathway. The antioxidant activity in the low concentration range of the compounds (1-4 μM) with a peroxyl radical scavenging capacity was proved by the ORAC (Oxygen Radical Absorbance Capacity) method and an ESR study. Similar concentrations of the compound also activated the Nrf2-ARE signaling with the Nrf2 translocation into the nuclear, then the expression of the antioxidant protein HO-1 increased. On the other hand, the high concentrations of both compounds (>10 μM) induced apoptosis with caspase 3/7 activation during suppression of the anti-apoptotic proteins, such as Bcl-XL and phosphorous Akt (pAkt). The Nrf2 expression was then activated in the nuclear, indicating that the Nrf2 plays a significant role in the cytoprotective effect against the toxicity of the compounds. These results indicated that the compounds have the dual functions of a cytoprotective effect and the apoptosis induction dependent on the treated concentrations through the Nrf2 activation. In addition, the results of all the assays involved in our previous studies suggested that the metabolite FxOH having a higher activity than the Fx, will be a bioavailable compound in biological systems.
在这项研究中，通过 Nrf2-ARE 通路研究了可生物利用的海洋类胡萝卜素岩藻黄质醇 (FxOH) 及其前体物质岩藻黄质 (Fx) 的功能。通过 ORAC（氧自由基吸收能力）方法和 ESR 研究证明，这些化合物在低浓度范围内（1-4 μM）具有抗氧化活性，具有过氧自由基清除能力。相同浓度的化合物也能激活 Nrf2-ARE 信号，使 Nrf2 转位入核，然后抗氧化蛋白 HO-1 的表达增加。另一方面，两种化合物的高浓度 (>10 μM) 在抑制抗凋亡蛋白（如 Bcl-XL 和磷酸化 Akt (pAkt)）的同时，诱导细胞凋亡，激活 caspase 3/7。然后 Nrf2 在核内被激活，表明 Nrf2 在化合物毒性的细胞保护作用中起着重要作用。这些结果表明，这些化合物具有通过 Nrf2 激活的细胞保护作用和依赖于处理浓度的细胞凋亡诱导的双重功能。此外，我们之前所有研究中涉及的所有检测结果表明，具有更高活性的代谢物 FxOH 将是生物体系中具有生物利用度的化合物。
