[Mechanism of ginsenoside Rg1 regulating the activity of β secretase in N2a/APP695 cells].

Objective: To explore whether or not ginsenoside Rg1 can modify the metabolism of amyloid precursor protein (APP) and the generation of amyloid beta (Aβ) by nuclear factor-kappa B (NF-κB).

Methods: N2a/APP695 cells, a mutated APP-overexpressing neuronal cell line, was used to mimic the APP metabolism and Aβ generation in vitro. The BACE1 mRNA and protein levels were detected by RT-PCR (reverse transcription-polymerase chain reaction) and Western blot respectively. Then the expression levels and subcellular localization of NF-κB were detected by Western blot and confocal laser scanning microscope respectively.

Results: The treatment of ginsenoside Rg1 at a dose of 2.5 µmol/L decreased the levels of Aβ1-40 and Aβ1-42 (13.3 ± 4.3) ng/ml vs (12.0 ± 5.4) ng/ml in N2a/APP695 cells, decreased the protein level of BACE1 (BACE1/β-actin 0.26 ± 0.05), increased the protein level of NF-κB p65 (p-p65/p65 0.93 ± 0.02) and resulted in the translocation of NF-κB from cytoplasm to nucleus. Quinazoline inhibited the activation of NF-κB with a reduction of p-p65 and p-p65/p65 in N2a/APP695 cells and increased the BACE1 protein level. And the treatment of ginsenoside Rg1 showed similar changes in N2a/APP695 cells when compared with the treatment of quinazoline alone.

Conclusion: Ginsenoside Rg1 may modify the metabolism of APP by enhancing the nuclear binding of NF-κB to BACE1 promoter and inhibiting the transcription and translation of BACE1.