Neuroprotective effect of salidroside on hippocampal neurons in diabetic mice via PI3K/Akt/GSK-3β signaling pathway.

Abstract

BACKGROUND:

Diabetic encephalopathy is manifested by cognitive dysfunction. Salidroside, a nature compound isolated from Rhodiola rosea L, has the effects of anti-inflammatory and antioxidant, hypoglycemic and lipid-lowering, improving insulin resistance, inhibiting cell apoptosis, and protecting neurons. However, the mechanism by which salidroside alleviates neuronal degeneration and improves learning and memory impairment in diabetic mice remains unclear.

OBJECTIVE:

To investigate the effects and mechanisms of salidroside on hippocampal neurons in streptozotocin-induced diabetic mice.

MATERIALS AND METHODS:

C57BL/6 mice were randomly divided into 4 groups to receive either sham (control group (CON)), diabetes mellitus (diabetes group (DM)), diabetes mellitus + salidroside (salidroside group (DM + SAL)), and diabetes mellitus + salidroside + phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (diabetes mellitus + salidroside + LY294002 group (DM + SAL + LY294002)). After 12 weeks of diabetes onset, the cognitive behaviors were tested using Morris water maze. The number of hippocampal neurons was detected by Nissl staining. The expressions of PI3K, p-PI3K, Akt, p-Akt, GSK-3β, p-GSK-3β, cleaved caspase-3, caspase-3, Bax, Bcl-2, MAP2, and SYN in the hippocampus were detected by Western blot. Moreover, the expression of MAP2 and SYN in the hippocampus was further confirmed by immunofluorescence staining.

RESULTS:

Salidroside increased the time of diabetic mice in the platform quadrant and reduced the escape latency of diabetic mice. Salidroside also increased the expression of p-PI3K, p-Akt, p-GSK-3β, MAP2, SYN, Bcl-2, while suppressed the expression of cleaved caspase-3, caspase3, and Bax in the DM + SAL group compared with the DM group (P < 0.05). The Nissl staining showed that the number of hippocampus neurons in the DM + SAL group was increased with the intact, compact, and regular arrangement, compared with the DM groups (P < 0.05). Interestingly, the protective effects of salidroside on diabetic cognitive dysfunction, hippocampal morphological alterations, and protein expressions were abolished by inhibition of PI3K with LY294002.

CONCLUSIONS:

Salidroside exerts neuroprotective properties in diabetic cognitive dysfunction partly via activating the PI3K/Akt/GSK-3β signaling pathway.

• Authors: Xue-Hua Wang, Zhong-Fu Zuo, Lu Meng, Qi Yang, Pan Lv, Li-Pan Zhao, Xiao-Bai Wang, Yu-Fei Wang, Ying Huang, Cong Fu, Wen-Qiang Liu, Xue-Zheng Liu, De-Yu Zheng
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 240 Issue 9 Pg. 1865-1876 (Sep 2023) ISSN: 1432-2072 [Electronic] Germany
• PMID: 37490132 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• bcl-2-Associated X Protein
• Caspase 3
• Glycogen Synthase Kinase 3 beta
• Neuroprotective Agents
• Phosphatidylinositol 3-Kinase
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Proto-Oncogene Proteins c-bcl-2
• rhodioloside

Topics

• Animals
• Mice
• Apoptosis (drug effects)
• bcl-2-Associated X Protein (metabolism)
• Caspase 3 (metabolism)
• Diabetes Mellitus, Experimental (drug therapy, metabolism)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Hippocampus (drug effects, pathology)
• Mice, Inbred C57BL
• Neurons
• Neuroprotective Agents (pharmacology, therapeutic use)
• Phosphatidylinositol 3-Kinase (metabolism, pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism, pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Signal Transduction
• Brain Diseases (drug therapy)
• Hypoglycemia (drug therapy)