Protective Effect and Molecular Simulation of Astragaloside A on PC12 Cells 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 cell damage model of PC 12 was established by 6-OHDA.This study examined cell proliferation rate,the re-lease of LDH(lactate dehydrogenase),cell apoptosis,activity of SOD(superoxide dismutase),GSH(glu-tathione),level of T-AOC(total antioxidant capacity)and Nrf2(nuclear factor erythroid 2-related factor 2)protein expression in cells to explore the protective effect of AS-Ⅳ on PC 12 cells and its mechanism.The compound was docked to Keap1(Kelch-like ECH-associated protein-1),a negative regulatory protein of Nrf2,and the molecu-lar dynamics simulation system of the"compound target"complex was established to further study its interaction mode.The results showed that compared with 6-OHDA model group,25,50 μmol/L AS-Ⅳ could significantly in-crease the proliferation rate of cells after 6-OHDA injury,reduce the content of LDH,inhibit apoptosis,up-regulate the levels of total GSH,T-AOC and SOD activity,and increase the expression of total Nrf2 in cells.The expression of nuclear Nrf2 was up-regulated and cytoplasm Nrf2 was down-regulated.AS-Ⅳ was docked to Keap1,the nega-tive regulatory protein of Nrf2,with a docking score of-7.03 kcal/mol,and the complex system remained stable in the simulation time of 50 ns,and the protein conformation was stable.The results showed that AS-Ⅳ could reduce the damage of PC 12 cells induced by oxidative stress and improve the endogenous antioxidant capacity of PC 12 cells,which might be related to the activation of transcription factor Nrf2.
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