Ginsenoside Rg1 protects against H(2)O(2)-induced neuronal damage due to inhibition of the NLRP1 inflammasome signalling pathway in hippocampal neurons in vitro

Oxidative stress and neuroinflammation are important in the pathogenesis of ageing and age-related neurodegenerative diseases, including Alzheimer’s disease. NADPH oxidase 2 (NOX2) is a major source of reactive oxygen species (ROS) in the brain. The nucleotide-binding oligomerisation domain (NOD)-like receptor protein 1 (NLRP1) inflammasome is responsible for the formation of pro-inflammatory molecules in neurons. Whether the NOX2-NLRP1 inflammasome signalling pathway is involved in neuronal ageing and age-related damage remains to be elucidated. Ginsenoside Rg1 (Rg1) is a steroidal saponin found in ginseng. In the present study, the primary hippocampal neurons were treated with H(2)O(2) (200 µM) and Rg1 (1, 5 and 10 µM) for 24 h to investigate the protective effects and mechanisms of Rg1 on H(2)O(2)-induced hippocampal neuron damage, which mimics age-related damage. The results showed that H(2)O(2) treatment significantly increased ROS production and upregulated the expression of NOX2 and the NLRP1 inflammasome, and led to neuronal senescence and damage to hippocampal neurons. Rg1 decreased ROS production, reducing the expression of NOX2 and the NLRP1 inflammasome in H(2)O(2)-treated hippocampal neurons. Furthermore, Rg1 and tempol treatment significantly decreased neuronal apoptosis and the expression of β-galactosidase, and alleviated the neuronal senescence and damage induced by H(2)O(2). The present study indicates that Rg1 may reduce NOX2-mediated ROS generation, inhibit NLRP1 inflammasome activation, and inhibit neuronal senescence and damage.