Numerous researches supported that oxidative stress and
inflammation play important roles in the development of
diabetic encephalopathy (
DEP).
Notoginsenoside R1 (NGR1), one major component of Panax notoginseng, is believed to have anti-oxidative, anti-inflammatory and neuroprotective properties. However, its
neuroprotective effects against
DEP and underlying mechanisms are still unknown. In this study, db/db mice as well as high-
glucose (HG)-treated HT22 hippocampal neurons were used as in vivo and in vitro models to estimate NGR1 neuroprotection. NGR1 administration for 10 weeks could ameliorate
cognitive dysfunction, depression-like behaviors,
insulin resistance,
hyperinsulinemia,
dyslipidemia, and
inflammation in db/db mice. NGR1 markedly decreased the oxidative stress induced by
hyperglycemia in hippocampal neurons. NGR1 significantly activated the
protein kinase B (Akt)/nuclear factor-erythroid 2-related factor2 (Nrf2) pathway, and inhibited NLRP3
inflammasome activation in hippocampal neurons, which might be essential for the
neuroprotective effects of NGR1. Further supporting these results, we observed that pretreatment with the
phosphatidylinositol 3-kinase inhibitor
LY294002 abolished NGR1-mediated
neuroprotective effects against oxidative stress and NLRP3
inflammasome activation in HG-treated HT22 hippocampal neurons. In conclusion, the present study demonstrates the
neuroprotective effects of NGR1 on
DEP by activating the Akt/Nrf2 pathway and inhibiting NLRP3
inflammasome activation. This study also provides a novel strategy for the application of NGR1 as a therapeutic agent for patients with
DEP.