Saponin of Rhizoma Polygonati inhibits neuronal apoptosis and ameliorates cognitive deficits in Alzheimer’s disease mice by modulating c-Abl/MST1 pathway

Saponin of Rhizoma Polygonati (SRP) is a key bioactive component obtained from Rhizoma Polygonati, has neuroprotection, antioxidant and anticancer effects. This research aimed to explore whether SRP improves cognitive deficits in Alzheimer's disease (AD) mice. Behavioral testing was performed by the Morris water maze test. Histopathological changes and neuronal apoptosis in mouse hippocampus were observed by Hematoxylin-eosin, Nissl staining, and TUNEL staining. The impact of SRP on amyloid β-protein (Aβ) and neurofibrillary tangles (NFTs) production was determined by immunofluorescence and Glycine silver staining. Western blot detected c-Abl/Mammalian sterile 20 (STE20)-like kinase 1 (MST1) pathway, apoptosis-related protein, and Tau phosphorylation level. AD mice exhibit cognitive deficits compared to normal mice, and SRP ameliorates cognitive deficits. The hippocampal tissues of AD mice showed neuronal damage and apoptosis, with Aβ deposition, loss of Nissl bodies and formation of NFTs. SRP attenuated neuronal damage in AD mice, inhibited Aβ deposition and NFTs formation. Additionally, SRP blocked the c-Abl/MST1 pathway in AD mice. c-Abl inhibitor enhanced the neuroprotective effect of SRP in AD mice, while c-Abl agonist weakened this effect. SRP inhibits hippocampal histopathological damage and enhances cognitive ability in AD mice through blocking the c-Abl/MST1 pathway.