Li He-Mei, Jiang Yi-Xuan, Huang Pan-Ling, Li Bo-Cun, Pan Zi-Yu, Li Yu-Qing, Xia Xing
College of Pharmacy, Guangxi University of Chinese Medicine Nanning 530200, China.
College of Public Health and Management, Guangxi University of Chinese Medicine Nanning 530200, China.
Zhongguo Zhong Yao Za Zhi. 2022 Jan;47(2):484-491. doi: 10.19540/j.cnki.cjcmm.20210901.703.
Amyloid β-protein(Aβ) deposition in the brain is directly responsible for neuronal mitochondrial damage of Alzheimer's disease(AD) patients. Mitophagy, which removes damaged mitochondria, is a vital mode of neuron protection. Ginsenoside Rg_1(Rg_1), with neuroprotective effect, has displayed promising potential for AD treatment. However, the mechanism underlying the neuroprotective effect of Rg_1 has not been fully elucidated. The present study investigated the effects of ginsenoside Rg_(1 )on the autophagy of PC12 cells injured by Aβ_(25-35) to gain insight into the neuroprotective mechanism of Rg_1. The autophagy inducer rapamycin and the autophagy inhi-bitor chloroquine were used to verify the correlation between the neuroprotective effect of Rg_1 and autophagy. The results showed that Rg_1 enhanced the viability and increased the mitochondrial membrane potential of Aβ-injured PC12 cells, while these changes were blocked by chloroquine. Furthermore, Rg_(1 )treatment increased the LC3Ⅱ/Ⅰ protein ratio, promoted the depletion of p62 protein, up-regulated the protein levels of PINK1 and parkin, and reduced the amount of autophagy adaptor OPTN, which indicated the enhancement of autophagy. After the silencing of PINK1, a key regulatory site of mitophagy, Rg_1 could not increase the expression of PINK1 and parkin or the amount of NDP52, whereas it can still increase the LC3Ⅱ/Ⅰ protein ratio and promote the depletion of OPTN protein which indicated the enhancement of autophagy. Collectively, the results of this study imply that Rg_1 can promote autophagy of PC12 cells injured by Aβ, and may reduce Aβ-induced mitochondrial damage by promoting PINK1-dependent mitophagy, which may be one of the key mechanisms of its neuroprotective effect.
淀粉样β蛋白（Aβ）在大脑中的沉积直接导致阿尔茨海默病（AD）患者的神经元线粒体损伤。线粒体自噬可清除受损的线粒体，是神经元保护的重要方式。具有神经保护作用的人参皂苷Rg_1在AD治疗中显示出了良好的潜力。然而，Rg_1神经保护作用的潜在机制尚未完全阐明。本研究调查了人参皂苷Rg_1对Aβ_(25-35)损伤的PC12细胞自噬的影响，以深入了解Rg_1的神经保护机制。使用自噬诱导剂雷帕霉素和自噬抑制剂氯喹来验证Rg_1的神经保护作用与自噬之间的相关性。结果表明，Rg_1提高了Aβ损伤的PC12细胞的活力并增加了线粒体膜电位，而这些变化被氯喹阻断。此外，Rg_1处理增加了LC3Ⅱ/Ⅰ蛋白比率，促进了p62蛋白的消耗，上调了PINK1和帕金蛋白的水平，并减少了自噬衔接蛋白OPTN的量，这表明自噬增强。在自噬关键调节位点PINK1沉默后，Rg_1不能增加PINK1和帕金的表达或NDP52的量，而它仍然可以增加LC3Ⅱ/Ⅰ蛋白比率并促进OPTN蛋白的消耗，这表明自噬增强。总体而言，本研究结果表明，Rg_1可以促进Aβ损伤的PC12细胞的自噬，并可能通过促进PINK1依赖性线粒体自噬来减少Aβ诱导的线粒体损伤，这可能是其神经保护作用的关键机制之一。
