Pharmacodynamics and mechanisms of triterpene components from the leaves of Astragalus mongholicus Bunge in the treatment of Alzheimer's disease.

This study investigates the therapeutic potential and underlying mechanisms of triterpenoids (TR) derived from the leaves of Astragalus mongholicus Bunge for the treatment of Alzheimer's disease (AD). Eighteen triterpenoid compounds were identified in the TR fraction using UPLC-Q-TOF-MS. In the 3 × Tg-AD transgenic mouse model, the therapeutic efficacy of TR was assessed using a comprehensive approach that included the Morris water maze, histopathological analysis, transmission electron microscopy, and Western blotting. The findings revealed that TR significantly improved spatial learning and memory impairments, reduced hippocampal neuronal degeneration, and diminished the deposition of phosphorylated Tau (p-Tau) protein. Ultrastructural examination further confirmed that TR preserved mitochondrial integrity. Mechanistic studies showed that TR upregulated key mitophagy-related proteins in both PINK1/Parkin-dependent and -independent pathways. In conclusion, TR exerts neuroprotective effects by activating mitophagy through multiple pathways, highlighting its potential as a promising therapeutic candidate for AD. This study not only provides experimental evidence for the therapeutic potential of natural products targeting mitophagy in Alzheimer's disease but also expands the medicinal development value of the leaves of Astragalus mongholicus Bunge.