Center for Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, Yantai 264005, China.
Shandong Hongli Medical Animal Experimental Research Co., Jinan 250000, China.
Nutrients. 2022 Aug 26;14(17):3508. doi: 10.3390/nu14173508.
Rosmarinic acid (RA) is a natural polyphenolic compound with antioxidative property. With the present study, we aimed to evaluate the neuroprotective role of RA on Parkinson's disease using rotenone induced SH-SY5Y cell model of Parkinson's disease, the underlying mechanism of action of RA was also investigated. Cell viability, cell morphology, apoptosis, signaling protein phosphorylation and expression, cellular reactive oxygen species (ROS) production, ATP content, and mitochondrial membrane potential were tested in SH-SY5Y cells. RA showed a neuroprotective effect in a rotenone-induced SH-SY5Y cell model of Parkinson's disease with dose-dependent manner, it reduced cell apoptosis and restored normal cell morphology. RA not only decreased levels of α-synuclein and Tau phosphorylation but also elevated the contents of AMPK phosphorylation, Akt phosphorylation, and PGC-1α. RA restored the reduced mitochondrial membrane potential and ATP content as well as inhibited rotenone-induced ROS overproduction. Further findings demonstrated that the neuroprotective role of RA was partially due to the inhibition of Abl tyrosine kinase. RA treatment suppressed the hyperphosphorylation of Abl Y412 and CrkII Y221 induced by rotenone. Nilotinib, a specific inhibitor of Abl, elicited a similar neuroprotective effect as that of RA. The present study indicates that RA has a property of neuroprotection against rotenone, and the neuroprotective effect is partially attributed to the inhibition of Abl.
迷迭香酸（RA）是一种具有抗氧化性质的天然多酚化合物。本研究旨在通过鱼藤酮诱导的帕金森病 SH-SY5Y 细胞模型评估 RA 对帕金森病的神经保护作用，并探讨 RA 的作用机制。在 SH-SY5Y 细胞中测试细胞活力、细胞形态、细胞凋亡、信号蛋白磷酸化和表达、细胞活性氧（ROS）产生、ATP 含量和线粒体膜电位。RA 在鱼藤酮诱导的帕金森病 SH-SY5Y 细胞模型中表现出剂量依赖性的神经保护作用，降低细胞凋亡并恢复正常细胞形态。RA 不仅降低了α-突触核蛋白和 Tau 磷酸化水平，还提高了 AMPK 磷酸化、Akt 磷酸化和 PGC-1α 的含量。RA 恢复了降低的线粒体膜电位和 ATP 含量，并抑制了鱼藤酮诱导的 ROS 过度产生。进一步的研究结果表明，RA 的神经保护作用部分归因于 Abl 酪氨酸激酶的抑制。RA 处理抑制了鱼藤酮诱导的 Abl Y412 和 CrkII Y221 的过度磷酸化。Abl 的特异性抑制剂 nilotinib 产生了与 RA 相似的神经保护作用。本研究表明，RA 具有对抗鱼藤酮的神经保护作用，其神经保护作用部分归因于 Abl 的抑制。
