Ginkgo biloba extract mediates HT22 cell proliferation and migration after oxygen-glucose deprivation/reoxygenation via regulating RhoA-ROCK2 signalling pathway.

Abstract

Vascular dementia (VD) is a neurocognitive disorder resulting from cerebral vascular disorders, leading to the demise of neurons and cognitive deficits, posing significant health concerns globally. Derived from Ginkgo biloba leaves, EGb761 is a potent bioactive compound widely recognized for its benefits in treating cerebrovascular diseases. Previous studies have demonstrated that the administration of EGb761 to VD rats enhances the proliferation, differentiation, and migration of neurons, effectively alleviating cognitive dysfunction. However, the specific mechanisms by which EGb761 exerts its remedial influence on VD persist in ambiguity. This investigation utilized an integrated approach incorporating network pharmacology with experimental procedures on HT-22 mouse hippocampal neuronal cells amidst oxygen-glucose deprivation and reoxygenation (OGD/R) to delve into certain repercussions of EGb761 on cell proliferation and migration. Results revealed that ras homolog family member A (RHOA) and B-cell lymphoma 2 (BCL-2) are potential targets of Ginkgo biloba leaves. Target genes are mainly enriched in pathways including those involved in growth hormone synthesis, secretion and action and the neurotrophin signalling pathway. Cellular experiments further demonstrated that the application of EGb761 notably enhanced the viability, proliferation, and migration of HT22 cells subjected to OGD/R through RhoA-ROCK2 pathway. In conclusion, our findings indicated that EGb761 significantly enhances neuronal proliferation and migration following OGD/R injury by targeting the RhoA-ROCK2 signalling pathway, thus offering valuable insights into its potential as a treatment for VD.