• Tan-Zhen Xu, Xiao-Yan Shen, Ling-Ling Sun, Ya-Li Chen, Bi-Qiong Zhang, Da-Ke Huang, and Wei-Zu Li.
• Department of Pharmacology, Key Laboratory of Anti‑inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
• Int. J. Mol. Med. 2019 Feb 1; 43 (2): 717-726.

AbstractOxidative 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 H2O2 (200 µM) and Rg1 (1, 5 and 10 µM) for 24 h to investigate the protective effects and mechanisms of Rg1 on H2O2‑induced hippocampal neuron damage, which mimics age‑related damage. The results showed that H2O2 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 H2O2‑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 H2O2. The present study indicates that Rg1 may reduce NOX2‑mediated ROS generation, inhibit NLRP1 inflammasome activation, and inhibit neuronal senescence and damage.

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