Available online 28 December 2022

Rg1 improved T2DM-induced cognitive dysfunction and neuronal lesion.

Rg1 ameliorated T2DM-induced Aβ generation and synaptic dysfunction.

Rg1 decreased ROS production and NOX2 expressions in brain of T2DM mice.

Rg1 suppressed PLC–CN–NFAT1 signaling in brain of T2DM mice.

As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) has promising neuroprotective properties, but the effect and mechanism in diabetes-associated cognitive dysfunction (DACD) deserve further investigation.

After establishing the T2DM model with a high-fat diet and STZ intraperitoneal injection, Rg1 was given for 8 weeks. The behavior alterations and neuronal lesions were judged using the open field test (OFT) and Morris water maze (MWM), as well as HE and Nissl staining. The protein or mRNA changes of NOX2, p-PLC, TRPC6, CN, NFAT1, APP, BACE1, NCSTN, and Aβ1-42 were investigated by immunoblot, immunofluorescence or qPCR. Commercial kits were used to evaluate the levels of IP3, DAG, and calcium ion (Ca2+) in brain tissues.

Rg1 therapy improved memory impairment and neuronal injury, decreased ROS, IP3, and DAG levels to revert Ca2+ overload, downregulated the expressions of p-PLC, TRPC6, CN, and NFAT1 nuclear translocation, and alleviated Aβ deposition in T2DM mice. In addition, Rg1 therapy elevated the expression of PSD95 and SYN in T2DM mice, which in turn improved synaptic dysfunction.

Rg1 therapy may improve neuronal injury and DACD via mediating PLC–CN–NFAT1 signal pathway to reduce Aβ generation in T2DM mice.

Type II Diabetes Mellitus

Cognitive dysfunction

Ginsenoside Rg1

Calcium homeostasis

Phospholipase C

One-way analysis of variance

Amyloid precursor protein

β-carboxy-terminal fragments

Diabetes-associated cognitive dysfunction

Inositol trisphosphate

Nuclear factor of activated T-cells 1

Postsynaptic density 95

Reactive oxygen species

Type II diabetes mellitus

Transient receptor potential channel 6

© 2022 The Korean Society of Ginseng. Publishing services by Elsevier B.V.