Astragalus polysaccharide exerts anti-Parkinson via activating the PI3K/AKT/mTOR pathway to increase cellular autophagy level in vitro

Astragalus polysaccharide (APS) is a bioactive macromolecule, which has been used to alleviate the development of Parkinson's disease (PD), while its mechanism is still unresolved. As is generally accepted that autophagy has an important link with PD, thus it is reasonable to hypothesize that APS was involved in autophagy pathway for the presence of anti-PD. To verify this hypothesis, PD model was induced by 100 mu M 6-hydroxydopamine (6-HODA) in PC12 cells and then treated with different concentration of APS. Results showed that APS could increase cell viability and the level of autophagy, improve the formation of autophagosome, promote the conversion of LC3-I to LC-II, showing APS could improve autophagy level. Moreover, APS could down-regulate the expression of pAICI and pmTOR, and up-regulate the expression of PTEN. While these proteins are involved in PI3K/AKT/mTOR pathway, we then knocked down (KD) endogenous P13K protein (the PI3K/AKT/mTOR pathway receptor protein) in PC12 cells. Results showed that these events regulated by APS were reversed in P13K KD cells, shown that APS activated autophagy through PI3K/AKT/mTOR pathway for treating PD. Altogether, APS has the role of increasing autophagy, and this event was responsible for inhibiting PI3K protein to activate PI3K/AKT/mTOR pathway. (C) 2020 Published by Elsevier B.V.