Ginsenoside Rg1 protects against neuronal degeneration induced by chronic dexamethasone treatment by inhibiting NLRP-1 inflammasomes in mice

Glucocorticoids (GCs) are known to alter neuronal plasticity, impair learning and memory and play important roles in the generation and progression of Alzheimer's disease. There are no effective drug options for preventing neuronal injury induced by chronic GC exposure. Ginsenoside Rg1 (Rg1) is a steroidal saponin found in ginseng. The present study investigated the neuroprotective effect of Rg1 on neuroinflammation damage induced by chronic dexamethasone (5 mg/kg for 28 days) exposure in male mice. Our results showed that Rg1 (2 and 4 mg/kg) treatment increased spontaneous motor activity and exploratory behavior in an open field test, and increased the number of entries into the new object zone in a novel object recognition test. Moreover, Rg1 (2 and 4 mg/kg) treatment significantly alleviated neuronal degeneration and increased MAP2 expression in the frontal cortex and hippocampus. Additionally, inhibition of NLRP-1 inflammasomes was also involved in the mechanisms underlying the effect of Rg1 on GC-induced neuronal injury. We found that Rg1 (2 and 4 mg/kg) treatment increased the expression of glucocorticosteroid receptor and decreased the expression of NLRP-1, ASC, caspase-1, caspase-5, IL-1 beta and IL-18 in the hippocampus in male mice. The present study indicates that Rg1 may have protective effects on neuroinflammation and neuronal injury induced by chronic GC exposure.