Astragalin Ameliorates Cognitive Dysfunction Through Inhibiting PI3K/Akt-MTOR-Mediated Autophagic Flow in Hippocampal Neurons of APP/PS1 Mice

Abstract

Astragalin (AST), a natural small molecule flavonoid, can exert anti-oxidant, anti-inflammatory and anti-cancer impacts by regulating autophagy. However, the potential mechanism of the neuroprotective effect of AST on neurological disorders such as Alzheimer’s disease (AD) is still not clear. In the present study, we firstly screened AST for the treatment of AD from the ingredients of Chinese medicines such as Acori tataninowii Rhizoma, Eucommiae Cortex, Paeoniae Radix Alba through the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database. And then we found that AST could improve the cognitive abilities of APP/PS1 mice by Step-down passive avoidance (SDA) and Morris Water Maze (MWM) Test. Further, we identified that AST diminished Aβ plaques deposition in the brains of APP/PS1 mice and Aβ as well as Aβ42 levels in the serum of APP/PS1 mice. Next, microtubule-associated protein 1 light chain 3B (LC3B), p62, Beclin-1, ATG5, ATG12, LAMP-1 were observed to be co-expressed with NeuN in the hippocampus of APP/PS1 mice by immunofluorescent multiplex staining, while AST was able to activate autophagy and maintain autophagic flow in hippocampal neurons of APP/PS1 mice by western blot (WB) analysis. Finally, AST reduced the expressions of p-PI3K, p-Akt, p-mTOR by WB analysis. Taken together, we confirmed that AST may play key neuroprotective effects on APP/PS1 mice by inhibiting the PI3K/Akt-mTOR signaling pathway to activate autophagy and keep autophagic flow smooth.

Regulation of autophagy by plant‐based polyphenols: A critical review of current advances in glucolipid metabolic diseases and food industry applications

“…Simultaneously, research also found IL‐1β levels in the cortex correlates positively with Beclin‐1 and LC3‐II and inversely with p62 (François et al., 2014). An increasing body of evidence in cell and animal models supports that autophagy responses, regulated by polyphenols, play a pivotal role neuroinflammation (Qiu et al., 2020; Yang et al., 2022). In lipopolysaccharides (LPS)‐treated BV2 microglia, UroA treatment induced autophagy by increasing LC3 HiBiT reporter activity, contributing to its antineuroinflammatory activity (Velagapudi et al., 2019).…”