Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Sunshine Southern Avenue, Fang-Shan District, Beijing 102488, China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian-Nong-Tan Street, Xi-Cheng District, Beijing 100050, China.
Phytomedicine. 2022 Sep;104:154281. doi: 10.1016/j.phymed.2022.154281. Epub 2022 Jun 16.
Parkinson's disease (PD) is the second most common neurodegenerative disease featured to mitochondrial dysfunction in neuronal cells. Dynamin-related protein 1 (Drp1) is an important regulator of mitochondrial fission and subsequent mitophagy. Mangiferin (MGF) is a glucosyl xanthone mainly derived from Mangifera indica L., possessing multifaceted properties, e.g., antioxidant, anti-inflammatory, and enhancement of cognitive ability. Besides, it can cross the blood-brain barrier, thereby exerting a neuroprotective effect. However, so far, MGF's effect in balancing mitochondrial homeostasis via regulation of Drp1 level and mitophagic pathway in PD remains rarely reported.
We aimed to investigate the neuroprotective effect of MGF against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and examine the possible mechanisms.
We utilized C57BL/6 mice exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Behavioral parameters, containing the open field test, balance beam, pole test, and rotarod test, assessed the locomotor activity; immunohistochemistry assessed the number of TH-positive neurons; transmission electron microscopy detected ultrastructural mitochondrial morphology in the dopaminergic neuron; complex I enzymatic activity microplate assay kit measured the mitochondrial complex I activity; ATP determination kit measured ATP levels in mitochondria isolated from cells or striatal tissues; western blot measured the levels of Drp1 and mitophagic proteins.
We observed that MGF could mitigate motor deficiency and improve the expression of tyrosine hydroxylase in the substantia nigra of MPTP-induced PD mice. Furthermore, MGF not only ameliorated mitochondrial ultrastructure, but also improved mitochondrial ATP content. Within mitochondria, MGF could reduce Drp1 expression and reverse the expressions of mitophagic proteins, including PINK1, Parkin, NIX, BNIP3, FUNDC1, and p62.
Present study indicates that MGF benefits mitochondrial networks by recovering mitochondrial ultrastructure and ATP contents, reducing mitochondrial Drp1, and modulating mitophagic proteins in the MPTP-induced PD mice model, which revealed a novel acting mechanism of MGF in PD's treatment.
帕金森病（PD）是第二常见的神经退行性疾病，其特征在于神经元细胞中线粒体功能障碍。与动力相关蛋白 1（Drp1）是线粒体分裂和随后的线粒体自噬的重要调节剂。芒果苷（MGF）是一种主要来源于芒果的葡萄糖基黄烷酮，具有多种特性，例如抗氧化、抗炎和增强认知能力。此外，它可以穿过血脑屏障，从而发挥神经保护作用。然而，到目前为止，MGF 通过调节 Drp1 水平和 PD 中的噬线粒体途径来平衡线粒体稳态的作用很少有报道。
我们旨在研究芒果苷（MGF）对 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的 PD 小鼠模型的神经保护作用，并探讨其可能的机制。
我们使用 C57BL/6 小鼠暴露于 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）；行为参数，包括旷场试验、平衡梁、棒试验和转棒试验，评估运动活动；免疫组织化学评估 TH 阳性神经元的数量；透射电子显微镜检测多巴胺能神经元的超微结构线粒体形态；线粒体复合物 I 酶活性微量板测定试剂盒测定线粒体复合物 I 活性；ATP 测定试剂盒测定细胞或纹状体组织分离的线粒体中的 ATP 水平；western blot 测定 Drp1 和噬线粒体蛋白的水平。
我们观察到 MGF 可以减轻运动缺陷并提高 MPTP 诱导的 PD 小鼠黑质中酪氨酸羟化酶的表达。此外，MGF 不仅改善了线粒体超微结构，而且还改善了线粒体 ATP 含量。在线粒体中，MGF 可以降低 Drp1 的表达并逆转噬线粒体蛋白的表达，包括 PINK1、Parkin、NIX、BNIP3、FUNDC1 和 p62。
本研究表明，MGF 通过恢复线粒体超微结构和 ATP 含量、减少线粒体 Drp1 以及调节 MPTP 诱导的 PD 小鼠模型中的噬线粒体蛋白来改善线粒体网络，揭示了 MGF 在 PD 治疗中的新作用机制。
