Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, P.R. China.
Food Funct. 2020 Feb 26;11(2):1425-1440. doi: 10.1039/c9fo02288k.
Although Parkinson's disease (PD) is the second most common neurodegenerative disorder, the preventative or therapeutic agents for the treatment of PD are limited. Eucommia ulmoides Oliver (EuO) is widely used as a traditional herb to treat various diseases. EuO bark extracts have been reported to possess anti-PD activity. Here, we investigated whether extracts of EuO leaves (EEuOL) also have therapeutic effects on PD since similar components and clinical applications have been found between barks and leaves of this tree. We identified the chemical composition of EEuOL by HPLC-Q-TOF-MS and tested the anti-PD effect of EEuOL using the zebrafish PD model. As a result, 28 compounds including 3 phenolic acids, 7 flavonoids, and 9 iridoids were identified. EEuOL significantly reversed the loss of dopaminergic neurons and neural vasculature and reduced the number of apoptotic cells in zebrafish brain in a concentration-dependent manner. Moreover, EEuOL relieved locomotor impairments in MPTP-modeled PD zebrafish. We also investigated the underlying mechanism and found that EEuOL may activate autophagy, contributing to α-synuclein degradation, therefore alleviating PD-like symptoms. Molecular docking simulation implied the interaction between autophagy regulators (Pink1, Beclin1, Ulk2, and Atg5) and phenolic acids of EEuOL, affirming the involvement of autophagy in EEuOL-exerted anti-PD action. The overall results indicated the anti-PD effect of EEuOL, opening the possibility to use the extract in PD treatment.
虽然帕金森病（PD）是第二常见的神经退行性疾病，但用于治疗 PD 的预防或治疗药物有限。杜仲（EuO）被广泛用作治疗各种疾病的传统草药。据报道，杜仲树皮提取物具有抗 PD 活性。在这里，我们研究了杜仲叶提取物（EEuOL）是否也对 PD 具有治疗作用，因为在这种树的树皮和叶子之间发现了类似的成分和临床应用。我们通过 HPLC-Q-TOF-MS 鉴定了 EEuOL 的化学成分，并使用斑马鱼 PD 模型测试了 EEuOL 的抗 PD 作用。结果，鉴定出 28 种化合物，包括 3 种酚酸、7 种类黄酮和 9 种环烯醚萜。EEuOL 以浓度依赖的方式显著逆转了多巴胺能神经元和神经血管的丧失，并减少了斑马鱼大脑中凋亡细胞的数量。此外，EEuOL 缓解了 MPTP 诱导的 PD 斑马鱼的运动障碍。我们还研究了潜在的机制，发现 EEuOL 可能通过激活自噬，促进α-突触核蛋白降解，从而缓解 PD 样症状。分子对接模拟表明自噬调节剂（Pink1、Beclin1、Ulk2 和 Atg5）与 EEuOL 中的酚酸之间存在相互作用，证实了自噬在 EEuOL 发挥抗 PD 作用中的参与。总的来说，这些结果表明了 EEuOL 的抗 PD 作用，为将其用于 PD 治疗开辟了可能性。
