Ginkgo biloba extract increases neurite outgrowth and activates the Akt/mTOR pathway

Introduction Standardized Ginkgo biloba extract (GBE) has demonstrated efficacy in the cognitive functional neuropsychiatric symptoms of patients with Alzheimer's disease. With regard to its underlying molecular mode of action, first evidence was provided that GBE was able to modulate neuronal outgrowth in vitro, but the mechanisms underlying GBE effects on neuroplasticity remain unclear.

Aim In this study, we investigated the effect of GBE on neurite outgrowth using SH-SY5Y neuroblastoma cells.

Method The effects of the GBE LI1370 on neurite outgrowth in a 2D and 3D surface culture were compared to those of nerve growth factor (NGF, 50 ng/ml) which was used as a positive control. We evaluated several parameters of neurite outgrowth such as the neurite number, total neurite length and extend of branching. In addition, we assessed the effects of GBE on the Akt/mTOR pathway, which is known to promote neuroplasticity induced by nerve growth factors.

Results GBE (10 and 100 μg/ml) significantly increased neurite outgrowth in the 2D as well as 3D culture model after 3 days of treatment, the n effect was comparable to that of NGF. With respect to the Akt/mTOR pathway, GBE treatment induced an increase of phosphorylated IGF1R (Tyr1135/Tyr1136), Akt (Ser473), TSC2 (Ser939), mTOR (Ser2448), PTEN (Ser380) and GSK3β (Ser9).

Conclusion These findings indicate that GBE promotes neurite growth and activates the PI3K/Akt/mTOR pathway, suggesting that this plant extract supports neuronal plasticity.

Acknowledgements We thank Vifor Pharma Switzerland, the Swiss National Science Foundation (Grant #31003A_179294) and the Synapsis Foundation - Alzheimer Research Switzerland ARS for their financial support and fundings.

Publikationsverlauf

Artikel online veröffentlicht:
13. Juni 2022