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

Int J Biol Macromol. 2020 Jun 15;153:349-356. doi: 10.1016/j.ijbiomac.2020.02.282. Epub 2020 Feb 26.


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 μM 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 LC3-II, showing APS could improve autophagy level. Moreover, APS could down-regulate the expression of pAKT 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 PI3K protein (the PI3K/AKT/mTOR pathway receptor protein) in PC12 cells. Results showed that these events regulated by APS were reversed in PI3K 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.

Keywords: Astragalus polysaccharide; Autophagy; Parkinson's disease.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Astragalus Plant / chemistry*
  • Autophagy / drug effects*
  • Cell Survival / drug effects
  • PC12 Cells
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation / drug effects
  • Polysaccharides / pharmacology*
  • Polysaccharides / therapeutic use
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Messenger / genetics
  • Rats
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Up-Regulation / drug effects


  • Polysaccharides
  • RNA, Messenger
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases