Protective Effect and Molecular Simulation of Astragaloside A on PC12Cells Damaged by Neurotoxin

This paper proved the protective effect of AS-IV (Astragaloside A) on PC12 cells damaged by the neurotoxin 6-OHDA (6-hydroxydopamine) and explored its mechanism through molecular simulation. The celldamage model of PC12 was established by 6-OHDA. This study examined cell proliferation rate, the release of LDH (lactate dehydrogenase), cell apoptosis, activity of SOD (superoxide dismutase), GSH (glutathione), level of T-AOC (total antioxidant capacity) and Nrf2 (nuclear factor erythroid 2-related factor 2) proteinexpression in cells to explore the protective effect of AS-IV on PC12 cells and its mechanism. The compound wasdocked to Keap1 (Kelch-like ECH-associated protein-1), a negative regulatory protein of Nrf2, and the molecular dynamics simulation system of the “compound target” complex was established to further study its interactionmode. The results showed that compared with 6-OHDA model group, 25, 50 μmol/L AS-IV could significantly increase the proliferation rate of cells after 6-OHDA injury, reduce the content of LDH, inhibit apoptosis, up-regulatethe levels of total GSH, T-AOC and SOD activity, and increase the expression of total Nrf2 in cells. The expressionof nuclear Nrf2 was up-regulated and cytoplasm Nrf2 was down-regulated. AS-IV was docked to Keap1, the negative regulatory protein of Nrf2, with a docking score of −7.03 kcal/mol, and the complex system remained stable inthe simulation time of 50 ns, and the protein conformation was stable. The results showed that AS-IV could reducethe damage of PC12 cells induced by oxidative stress and improve the endogenous antioxidant capacity of PC12cells, which might be related to the activation of transcription factor Nrf2.