Effects of ginsenoside on cellular model of Alzheimer disease induced by protein phosphatase inhibitor okadaic acid / 中国药理学通报

ABSTRACT

Aim To investigate the effects of ginsenoside(GS) on phosphorylation of tau protein,microtubule,cellular apoptosis and its related factors in cellular model of Alzheimer disease(AD) induced by the protein phosphatase 1 and 2A inhibitor okadaic acid(OA).Methods The human neuroblastoma cell line SK-N-SH cells were cultured with GS for 24 h,the culture medium was changed,and then incubated with OA 10 nmol?L-1 for 6 h.The changes of cell morphology were observed by inverted microscope.The laser confocal microscopy was used to observe the microtubule changes.Western blot was applied to determine the expression of phosphorylation of tau protein,and apoptosis-regulating factors Bcl-2,Bax and Caspase-3.The changes of apoptotic cells were observed by TUNEL method.Results The normal SK-N-SH cells spread well.OA-treated cells showed that the cell axons and the microtubules were broken and decreased under the inverted microscope and laser confocal microscope.Preincubation of GS demonstrated the significantly protective effects against the morphologic damage induced by OA.In OA-treated group,the phosphorylation of tau protein at Ser-199/202 and Ser-404 sites was higher than that in normal group,and the non-phosphorylation of tau protein at the same sites was lower;Incubation of GS at the dose of 50 mg?L-1 and 100 mg?L-1 with the cells decreased the phosphorylation of tau protein Ser-199/202 and Ser-404 sites.GS group at the dose of 50 mg?L-1 and 100 mg?L-1 decreased the expression of at non-phosphorylation of tau protein at the Ser202 site.The apoptotic cells were not found in normal group.The number of apoptotic cells were obviously increased.the expression of Bax and caspase-3 significantly enhanced,and Bcl-2 expression decreased in the OA-treated model group.GS significantly decreased the apoptotic cell number of nerve cells,inhibited the expression of Bax and caspase-3.Conclusion GS can protect the nerve cells from pathological change induced by OA.Maybe because it can inhibit the hyperphosphorylation of tau protein and protect the nerve cells from apoptosis,thus GS may have potential to treat Alzheimer disease.