Zhao Chengmu, Yue Juan, Xie Yu, Liu Bo, Xu Shuaishuai, Zhi Dejuan, Wang Dongsheng
School of Pharmacy, Lanzhou University, No. 199 Donggang West Road, Lanzhou, Gansu, 730000, China.
Frontiers Science Center for Rare Isotopes, No. 222 Tianshui South Road, Lanzhou, Gansu, 730000, China.
Mol Neurobiol. 2025 May 6. doi: 10.1007/s12035-025-05017-x.
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the abnormal deposition of amyloid-beta (Aβ) peptides and neurofibrillary tangles (NFTs). Ginsenosides, the primary active constituents in ginseng, exhibit potential in combating AD. In our previous work, the ginsenoside SumI was demonstrated to have superior anti-AD activity compared to other ginsenosides when used alone. This study revealed that SumI effectively decreased the lysosomal pH, promoted autophagosome formation, increased autophagic flux, and facilitated the transport of misfolded proteins to lysosomes for degradation in Caenorhabditis elegans. SumI activated the HLH-30 transcription factor by triggering a lipid-catabolic response akin to starvation. bec-1 RNAi significantly abrogated the anti-AD effect of SumI. Our findings indicate that SumI mitigated protein aggregation by activating the autophagy-lysosome pathway in C. elegans and provide scientific evidence that ginsenoside composition could be a potential therapeutic agent for treating or preventing AD.
阿尔茨海默病（AD）是一种复杂的神经退行性疾病，其特征在于β-淀粉样蛋白（Aβ）肽的异常沉积和神经原纤维缠结（NFTs）。人参皂苷是人参中的主要活性成分，在对抗AD方面具有潜力。在我们之前的工作中，人参皂苷SumI在单独使用时被证明与其他人参皂苷相比具有卓越的抗AD活性。本研究表明，SumI在秀丽隐杆线虫中有效降低了溶酶体pH值，促进了自噬体形成，增加了自噬通量，并促进了错误折叠蛋白向溶酶体的转运以进行降解。SumI通过引发类似于饥饿的脂质分解代谢反应激活了HLH-30转录因子。bec-1 RNA干扰显著消除了SumI的抗AD作用。我们的研究结果表明，SumI通过激活秀丽隐杆线虫中的自噬-溶酶体途径减轻了蛋白质聚集，并提供了科学证据证明人参皂苷成分可能是治疗或预防AD的潜在治疗剂。
