Li Yuqing, Shi Ruidie, Xia Lijie, Zhang Xuanming, Zhang Pengyu, Liu Siyuan, Liu Kechun, Sik Attila, Stoika Rostyslav, Jin Meng
Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Jinan 250103, China.
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China.
Int J Mol Sci. 2025 Mar 19;26(6):2762. doi: 10.3390/ijms26062762.
Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder, affecting an increasing number of older adults. Despite extensive research, a definitive cure remains elusive. Oliv. leaves (EUOL) have been reported to exhibit protective effects on neurodegenerative diseases, however, their efficacy, key active constituents, and pharmacological mechanisms are not yet understood. This study aims to explore the optimal constituents of EUOL regarding anti-PD activity and its underlying mechanisms. Using a zebrafish PD model, we found that the 30% ethanol fraction extract (EF) of EUOL significantly relieved MPTP-induced locomotor impairments, increased the length of dopaminergic neurons, inhibited the loss of neuronal vasculature, and regulated the misexpression of autophagy-related genes (, , , and ). Assays of key regulators involved in PD further verified the potential of the 30% EF against PD in the cellular PD model. Reverse phase protein array (RPPA) analysis revealed that 30% EF exerted anti-PD activity by activating 4E-BP1, which was confirmed by Western blotting. Phytochemical analysis indicated that cryptochlorogenic acid, chlorogenic acid, asperuloside, caffeic acid, and asperulosidic acid are the main components of the 30% EF. Molecular docking and surface plasmon resonance (SPR) indicated that the main components of the 30% EF exhibited favorable binding interactions with 4E-BP1, further highlighting the roles of 4E-BP1 in this process. Accordingly, these components were observed to ameliorate PD-like behaviors in the zebrafish model. Overall, this study revealed that the 30% EF is the key active constituent of EUOL, which had considerable ameliorative effects on PD by up-regulating 4E-BP1. This suggests that EUOL could serve as a promising candidate for the development of novel functional foods aimed at supporting PD treatment.
帕金森病（PD）是第二常见的进行性神经退行性疾病，影响着越来越多的老年人。尽管进行了广泛的研究，但仍未找到确切的治愈方法。据报道，橄榄叶（EUOL）对神经退行性疾病具有保护作用，然而，其功效、关键活性成分和药理机制尚不清楚。本研究旨在探索EUOL中抗帕金森病活性的最佳成分及其潜在机制。使用斑马鱼帕金森病模型，我们发现EUOL的30%乙醇提取物（EF）显著缓解了MPTP诱导的运动障碍，增加了多巴胺能神经元的长度，抑制了神经元血管系统的丧失，并调节了自噬相关基因（ 、 、 、 和 ）的错误表达。对帕金森病相关关键调节因子的检测进一步证实了30% EF在细胞帕金森病模型中抗帕金森病的潜力。反相蛋白阵列（RPPA）分析显示，30% EF通过激活4E-BP1发挥抗帕金森病活性，这一点通过蛋白质印迹法得到了证实。植物化学分析表明，隐绿原酸、绿原酸、车叶草苷、咖啡酸和车叶草苷酸是30% EF的主要成分。分子对接和表面等离子体共振（SPR）表明，30% EF的主要成分与4E-BP1表现出良好的结合相互作用，进一步突出了4E-BP1在此过程中的作用。因此，在斑马鱼模型中观察到这些成分改善了帕金森病样行为。总体而言，本研究表明30% EF是EUOL的关键活性成分，通过上调4E-BP1对帕金森病有显著的改善作用。这表明EUOL有望成为开发旨在支持帕金森病治疗的新型功能性食品的候选物。
