BACKGROUND: GSK-3β, has been shown to regulate APP cleavage resulting in the increased production of Aβ and the inhibition of the GSK-3β reduced the amyloid beta induced neurotoxicity in several studies.

OBJECTIVE: This study was designed to investigate the GSK-3β inhibitory effects of 6-gingerol and 6-shogaol the major components of Zingiber officinale could be able to recover the SHSY-5Y cells from Amyloid beta 1–42 oligomer and aggregate toxicity.

METHODS: SHSY-5Y (ATCC; CRL-2266) cells were maintained in Dulbecco’s modified eagle medium (DMEM, Gibco) containing 10% fetal calf serum, 100 U/mL penicillin, 50 μg/mL streptomycin, at 37°C and 5% CO2 in a humidified incubator. Cells were transferred to sterile 96-well e-plates at 5×10⁴ cells per well and followed real time for 78 hours via Xcelligence system. Ferulic acid was used as a positive control as a GSK-3β inhibitor at 4 μM dose and 6-gingerol and 6-shogaol were applied to the cells at 0.01 μM, 0.1 μM, 1 μM, 10 μM, 100 μM doses/50 μL with or without β-Amyloid 1–42 oligomers or aggregates. GSK-3β activity was determined by Kinase-Glo assay.

RESULTS: Both the amyloid beta aggregates and the oligomers had cytotoxic effect on SHSY-5Y cells followed by the real time cell analyzer system. 6-gingerol and 6 shogaol inhibited the GSK-3β enzyme up to % 20 levels in a dose dependent manner until 1 μM. However, parallel with the reduction of the inhibition for 6-shogaol over 1 μM, showed a toxicity itself on SHSY-5Y cells, whereas 6-gingerol did not show any cytotoxic effect at any doses applied.

CONCLUSIONS: 6-gingerol and 6-shogaol increased the cell viability followed in a real time manner after around 24 hours than the amyloid beta aggregate or oligomer toxicity as much as the ferulic acid could. Furthermore these effects supported the GSK-3β inhibitory effects of both compounds at low doses up to 1 μM. These results reveal that 6-gingerol and 6-shogaol the major components of Zingiber officinale help to recovery from amyloid beta toxicity which might further be investigated by clinical trials.

Search results

GSK-3beta inhibitory effects of 6-gingerol and 6-shogaol help to the recovery of SHSY-5Y cells after amyloid beta1–42 oligomer or aggregate toxicity