Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside Rg1 treatment protects against cognitive dysfunction via inhibiting PLC-CN-NFAT1 signaling in T2DM mice

  • Xianan Dong (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Liangliang Kong (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Lei Huang (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Yong Su (Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University) ;
  • Xuewang Li (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Liu Yang (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Pengmin Ji (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Weiping Li (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Weizu Li (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University)
  • Received : 2022.06.21
  • Accepted : 2022.12.20
  • Published : 2023.05.01
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Abstract

Background: 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. Methods: 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 Ab1-42 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. Results: 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. Conclusions: Rg1 therapy may improve neuronal injury and DACD via mediating PLC-CN-NFAT1 signal pathway to reduce Aβ generation in T2DM mice.

Keywords

Acknowledgement

This work was supported by the Major Projects of the Anhui Provincial Department of Education (KJ2020ZD14); the National Natural Science Foundation of China (81970630); and the Basic and Clinical Cooperative Research Promotion Program of Anhui Medical University (2019xkjT021).

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