The ameliorative effects of gastrodin on cognitive impairment in STZ-treated mice are associated with the modulation of hippocampal neurogenesis-related proteins and inhibition of the AGEs–RAGE axis

Hippocampal neurogenesis has been implicated in diabetic cognitive impairment (DCI). Gastrodin (Gas), the major bioactive ingredient of Gastrodia elata, has anti-inflammatory, antioxidant, and neuroprotective activities. This study investigated whether Gas protects against DCI and whether this is associated with the AGEs–RAGE axis and hippocampal neurogenesis-related proteins.

DCI was induced in mice by a high-fat diet plus streptozotocin. Mice received 25, 50, or 100 mg/kg Gas daily for four weeks, with metformin as positive control. Fasting blood glucose was monitored weekly.

Gas attenuated hyperglycemia and cognitive deficits in DCI mice. Gas treatment was accompanied by upregulation of neurogenesis- and synaptic-related proteins (C-Myc, Cyclin D1, NGN2, NeuroD1, PSD95, MAP2) and downregulation of AGEs, RAGE, GFAP, and pro-inflammatory factors. These findings suggest that Gas may alleviate HFD/STZ-induced cognitive impairment, possibly via AGEs–RAGE axis suppression and enhanced hippocampal neurogenesis-related protein expression.

However, this study was limited to a single animal model, relied mainly on correlative molecular data, and did not include pathway-blocking experiments. Further studies are needed to confirm causality and clinical relevance. We acknowledge the support and assistance provided by other members of the laboratory.

This research was funded by Hebei Provincial Administration of Traditional Chinese Medicine, grant number 2026046. Rui Li, Ri Gao and Runshi Zhao contributed equally to this work. Hebei University of Chinese Medicine, Shijiazhuang, 050200, China Rui Li, Jiali Yang, Lin Pei, Hu Chen & Guiqi Zhao The Fourth Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050000, China Rui Li, Jiali Yang, Yatao Du, Hongwei Yuan, Lin Pei, Hu Chen & Guiqi Zhao Hebei Provincial Center for Traditional Chinese Medicine Development, Shijiazhuang, 050057, China Beijing University of Chinese Medicine, Beijing, 100029, China Children’s Hospital of Hebei Province, Shijiazhuang, 050031, China The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050011, China Correspondence to Lin Pei, Hu Chen or Guiqi Zhao.

The authors declare no competing interests. The animal study protocol was approved by the Ethics Committee of Hebei University of Chinese Medicine (Ethics Approval No.: DWLL202303009). For research involving animals, the procedures followed were in accordance with the standards set forth in the eighth edition of “Guide for the Care and Use of Laboratory Animals”.