Molecular mechanism of ginsenoside Rg1 alleviating cognitive impairment in T2DM rats

Cognitive impairment is a common manifestation in patients with T2DM mellitus (T2DM). Ginsenoside Rg1 (GRg1) is the main active substance extracted from ginseng or Panax notoginseng. T2DM was induced by feeding rats with a high-sugar and high-fat diet combined with a low-dose intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) on an empty stomach. Subsequently, different concentrations of GRg1 (25, 50, 100 mg/kg/d) were used to intervene for 8 weeks and explore its therapeutic effects and potential mechanisms on cognitive impairment in T2DM rats. Our data suggested that administration of GRg1 improved insulin resistance, specifically manifesting in a reduction of insulin resistance index by approximately 57.1 % with high doses of GRg1 (100 mg/kg/d). Besides, it has been observed to lower cholesterol, triglycerides, and low-density lipoprotein by approximately 20–50 % in T2DM rats. In addition, GRg1 treatment dramatically improved the spatial memory and learning ability in T2DM rats. Furthermore, administration of GRg1 to the T2DM rats dose-dependently up-regulated ERKs phosphorylation and blunted phosphorylation of JNKs and p38. Furthermore, GRg1 treatment also dose-dependently increased the expression of Bcl-2 but inhibited the expression of Bax and Caspase 3 expression in T2DM rats brain cortex and hippocampus neurons. GRg1 effectively improves mild cognitive impairment in T2DM rats by inhibiting oxidative stress and reducing the apoptosis of neurons in the cerebral cortex and hippocampus.