Response Surface Methodology Optimization of Exosome-like Nanovesicles Extraction from Lycium ruthenicum Murray and Their Inhibitory Effects on Aβ-Induced Apoptosis and Oxidative Stress in HT22 Cells.

Exosome-like nanovesicles (ELNs) derived from plants are nanoscale vesicles isolated from edible plant sources. Lycium ruthenicum Murray (LRM) has garnered growing attention for its dietary value and therapeutic benefits. In this study, a PEG6000-based method was developed to isolate LRM-ELNs. Response surface methodology (RSM) was used to optimize the extraction conditions to obtain the optimal extraction efficiency. When PEG6000 concentration was at 11.93%, relative centrifugal force was 9720 g, and incubation time was 21.12 h, the maximum LRM-ELN yield was 4.24 g/kg. This optimization process yielded LRM-ELNs with a particle size of 114.1 nm and a surface charge of -6.36 mV. Additionally, LRM-ELNs mitigated Aβ-induced apoptosis in HT22 cells by enhancing mitochondrial membrane potential (MMP), lowering the Bax/Bcl-2 ratio, and reducing Cleaved Caspase-3 expression. Furthermore, LRM-ELNs alleviated Aβ-induced oxidative stress in HT22 cells by promoting the nuclear translocation of Nrf2 and upregulating the expression of HO-1 and NQO1. These findings indicate that LRM-ELNs exert protective effects against Aβ-induced damage in HT22 cells and may be considered as a potential dietary supplement for Alzheimer's disease prevention.