Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand.
Faculty of Dentistry, King Mongkut's Institute of Technology Ladkrabang, Ladkrabang, Bangkok 10520, Thailand.
Molecules. 2021 Aug 10;26(16):4843. doi: 10.3390/molecules26164843.
Parkinson's disease (PD) is a currently incurable neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta and α-synuclein aggregation. Accumulated evidence indicates that the saponins, especially from ginseng, have neuroprotective effects against neurodegenerative disorders. Interestingly, saponin can also be found in marine organisms such as the sea cucumber, but little is known about its effect in neurodegenerative disease, including PD. In this study, we investigated the anti-Parkinson effects of frondoside A (FA) from and ginsenoside Rg3 (Rg3) from in PD model. Both saponins were tested for toxicity and optimal concentration by food clearance assay and used to treat 6-OHDA-induced BZ555 and transgenic α-synuclein NL5901 strains in . Treatment with FA and Rg3 significantly attenuated DAergic neurodegeneration induced by 6-OHDA in BZ555 strain, improved basal slowing rate, and prolonged lifespan in the 6-OHDA-induced wild-type strain with downregulation of the apoptosis mediators, and , and upregulation of and . Interestingly, only FA reduced α-synuclein aggregation, rescued lifespan in NL5901, and upregulated the protein degradation regulators, including , , and . This study indicates that both FA and Rg3 possess beneficial effects in rescuing DAergic neurodegeneration in the 6-OHDA-induced model through suppressing apoptosis mediators and stimulating antioxidant enzymes. In addition, FA could attenuate α-synuclein aggregation through the protein degradation process.
帕金森病(PD)是一种目前无法治愈的神经退行性疾病,其特征是黑质致密部多巴胺能(DAergic)神经元丧失和α-突触核蛋白聚集。大量证据表明,皂苷,特别是来自人参的皂苷,对神经退行性疾病具有神经保护作用。有趣的是,皂苷也可以在海参等海洋生物中找到,但对其在神经退行性疾病(包括 PD)中的作用知之甚少。在这项研究中,我们研究了来自 和 中的 frondoside A(FA)和ginsenoside Rg3(Rg3)对 PD 模型的抗帕金森作用。通过食物清除试验测试了两种皂苷的毒性和最佳浓度,并将其用于治疗 6-OHDA 诱导的 BZ555 和转基因α-突触核蛋白 NL5901 菌株。FA 和 Rg3 的治疗显著减轻了 6-OHDA 在 BZ555 菌株中诱导的 DAergic 神经退行性变,改善了基础减速率,并延长了 6-OHDA 诱导的野生型菌株的寿命,下调了凋亡介质 和 ,上调了 和 。有趣的是,只有 FA 减少了α-突触核蛋白聚集,挽救了 NL5901 的寿命,并上调了包括 、 、 和 在内的蛋白降解调节剂。这项研究表明,FA 和 Rg3 都通过抑制凋亡介质和刺激抗氧化酶在挽救 6-OHDA 诱导的 模型中的 DAergic 神经退行性变方面具有有益作用。此外,FA 可以通过蛋白降解过程减轻α-突触核蛋白聚集。