Glycyrrhizic Acid Inhibits Hippocampal Neuron Apoptosis by Activating the PI3K/ AKT Signaling Pathway

Glycyrrhizic acid (GA), one of the main active substances in Glycyrrhiza, has anti-inflammatory, anti-viral, and neuroprotective effects. GA can significantly reduce cerebral infarction size in middle cerebral artery occlusion (MCAO) rats and suppress inflammatory responses. However, the underlying mechanism by which GA protects the neuronal system remains poorly understood. Cell proliferation and viability were tested using CCK-8 and Edu assays. The effects of GA on apoptosis were detected using flow cytometry and Tunel assays. Western blotting was performed to assess protein expression. Behavioral experiments were conducted using the Morris water maze and rotation tests. Infarct size was observed using TTC staining. We report that GA protects neurons by inhibiting apoptosis, mainly through the PI3K/AKT pathway in oxygen-glucose deprivation/reoxygenation (OGD/R) and MCAO rat models. GA increases the viability and proliferation of oxygen- and glucose-deprived hippocampal neurons. Hippocampal neuron apoptosis decreased after GA treatment in vitro and in vivo. Furthermore, we determined that GA treatment increased the active state of PI3K and its downstream protein p-AKT, whereas when using a specific inhibitor of PI3K, Y294002, the levels of p-PI3K and p-AKT decreased. Finally, we showed that GA treatment improved spatial memory and motor coordination in MCAO rats, while TTC staining showed that GA decreased cerebral infarct size in MCAO rats. We reveal that GA protects hippocampal neurons by inhibiting their apoptosis, mainly through the PI3K/AKT signaling pathway.