Based on Nrf2/Keap1 signaling pathways of ginseng CK targeted regulating A beta molecular mechanism research to protect the damaged neurons

[Speaker] Na Li:1
[Co-author] Qing Yang:1, Xin Sui:1, Zheng Xiao Shi:1, Hua Xiao Li:1, Dong Han:1, Bo Xiao Qu:1, Jun Dian Sui:1
1:Changchun University of Chinese Medicine, China

Objective:To study the protective effect of ginseng Compound K (CK) on damaged neurons and the molecular mechanism of downstream Nrf2/Keap1 signaling pathway regulation based on the amyloid protein. Methods:The binding,dissociation and dissociation equilibrium constants of CK in vitro were determined by Open SPR.The effect of CK on disaggregation of the amyloid protein oligomers was researched by SDS-PAGE.The effects of CK on the survival rate of SH-SY5Y cells were detected,and the ROS of injured neurons was detected by DCFH-DA at the cellular levels.Western blotting was used to detect the expression of BACE1, PS1and IDE. Results:CK could increase disaggregation ability of the amyloid protein by Open SPR;The monomer(M)can spontaneously form various oligomer forms in vitro,mainly including tetramer(T)and high molecular weight oligomers (H).The results of this experiment showed that the two oligomers forms of T and H were produced after incubation with amyloid protein,and the two oligomers were inhibited when co-incubated with CK.It is suggested that CK can target the oligomers and reduce the deposition of amyloid protein by SDS-PAGE.CK could improve the survival rate of SH-SY5Y cells damaged by the amyloid protein,CK reduced the generation of the fluorescence intensity of ROS.CK could activate Nrf2/Keap1 signal pathway which inhibited the expression of expression and deposition of amyloid,BACE1 and PS1 protein,promoted the expression of IDE protein by western blotting.Conclusion:CK could target on the amyloid protein and promoted disaggregation of the amyloid protein oligomers,inhibited the production of ROS and reduced oxidative stress of neuro cell which could protect the degeneration of nerve cell.The molecular mechanism may be related to the disaggregation and down-regulation of oligomers the amyloid protein expression in neuron cell by CK,which could targeted the regulation of amyloid oligomers disaggregation which inhibited BACE1 and PS1 expression,promoted the expression of IDE of activation of Nrf2/Keap1 signal pathway.

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