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已发表论文
黄芪甲苷通过减少 db/db 小鼠海马组织中β-淀粉样蛋白和 Tau 蛋白沉积改善认知障碍：一项基于 PET/CT 成像的研究
Authors Jiang L, Lu Y, Yin P, Liu D, Duan C, Wang Y
Received 3 March 2025
Accepted for publication 2 September 2025
Published 13 September 2025 Volume 2025:18 Pages 3477—3490
DOI https://doi.org/10.2147/DMSO.S526076
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Rebecca Conway
Lei Jiang,1,2,* Yanchao Lu,1,* Pei Yin,1 Dan Liu,1 Chengshuo Duan,1 Yong Wang1
1Department of Radiology and Nuclear Medicine, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, Shijiazhuang, Hebei, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yong Wang, Department of Radiology and Nuclear Medicine, The First Hospital of Hebei Medical University, No. 89, Donggang Road, Shijiazhuang, Hebei, People’s Republic of China, Email wangyong@hebmu.edu.cn
Purpose: Diabetic Cognitive Impairment is a frequent diabetes complication with few treatments. Astragaloside IV (AS-IV), a lanosterol-derived saponin, shows significant neuroprotection. This study used PET/CT to assess the effects of AS-IV on β-amyloid (Aβ) and tau protein buildup in the hippocampus of db/db mice and to investigate the underlying mechanisms involved.
Methods: Eighteen diabetic db/db mice were divided into three groups: a model group, and two treatment groups receiving AS-IV at 20 mg/kg and 40 mg/kg (n=6 each). A control group of db/m mice (n=6) was also included. Treated mice were administered AS-IV daily, while the model and control groups were administered saline for eight weeks. Biweekly, mice were assessed for body weight and fasting blood glucose. Insulin sensitivity was tested using the OGTT, and cognitive function was evaluated with the MWM. Aβ deposition was observed with 18F-AV45 PET and Congo red staining, tau protein deposition with 18F-MK6240 PET, and neurofibrillary tangles with silver staining. TNF-α levels and proteins related to the EGFR/NF-κB pathway were analyzed in blood and hippocampal tissue.
Results: The study found that AS-IV reduced weight gain (P < 0.05), lowered fasting glucose (P < 0.01– 0.001), and improved glucose tolerance (P < 0.05– 0.001) in db/db mice. Behavioral tests showed that AS-IV treatment decreased escape latency (P < 0.05– 0.01), increased time in the target quadrant (P < 0.05– 0.001), and raised the number of platform crossings (P < 0.05– 0.001). 18F-AV45 PET, 18F-MK6240 PET, Congo red staining and silver staining revealed reduced Aβ (P < 0.05– 0.001) and tau protein (P < 0.01) deposits in the hippocampus. ELISA and immunofluorescence assays indicated a significant decrease in TNF-α expression in serum (P < 0.05– 0.001) and hippocampus (P < 0.01– 0.001), while Western blot analyses showed inhibition of the EGFR/NF-κB signaling pathway.
Conclusion: This study found that AS-IV improved cognitive function in diabetic db/db mice by reducing the buildup of Aβ and tau proteins in the hippocampus via the TNF-α-activated EGFR/NF-κB pathway.
Keywords: astragaloside IV, diabetic cognitive impairment, β-amyloid, tau protein, in vivo, PET-CT
1Department of Radiology and Nuclear Medicine, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, Shijiazhuang, Hebei, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yong Wang, Department of Radiology and Nuclear Medicine, The First Hospital of Hebei Medical University, No. 89, Donggang Road, Shijiazhuang, Hebei, People’s Republic of China, Email wangyong@hebmu.edu.cn
Purpose: Diabetic Cognitive Impairment is a frequent diabetes complication with few treatments. Astragaloside IV (AS-IV), a lanosterol-derived saponin, shows significant neuroprotection. This study used PET/CT to assess the effects of AS-IV on β-amyloid (Aβ) and tau protein buildup in the hippocampus of db/db mice and to investigate the underlying mechanisms involved.
Methods: Eighteen diabetic db/db mice were divided into three groups: a model group, and two treatment groups receiving AS-IV at 20 mg/kg and 40 mg/kg (n=6 each). A control group of db/m mice (n=6) was also included. Treated mice were administered AS-IV daily, while the model and control groups were administered saline for eight weeks. Biweekly, mice were assessed for body weight and fasting blood glucose. Insulin sensitivity was tested using the OGTT, and cognitive function was evaluated with the MWM. Aβ deposition was observed with 18F-AV45 PET and Congo red staining, tau protein deposition with 18F-MK6240 PET, and neurofibrillary tangles with silver staining. TNF-α levels and proteins related to the EGFR/NF-κB pathway were analyzed in blood and hippocampal tissue.
Results: The study found that AS-IV reduced weight gain (P < 0.05), lowered fasting glucose (P < 0.01– 0.001), and improved glucose tolerance (P < 0.05– 0.001) in db/db mice. Behavioral tests showed that AS-IV treatment decreased escape latency (P < 0.05– 0.01), increased time in the target quadrant (P < 0.05– 0.001), and raised the number of platform crossings (P < 0.05– 0.001). 18F-AV45 PET, 18F-MK6240 PET, Congo red staining and silver staining revealed reduced Aβ (P < 0.05– 0.001) and tau protein (P < 0.01) deposits in the hippocampus. ELISA and immunofluorescence assays indicated a significant decrease in TNF-α expression in serum (P < 0.05– 0.001) and hippocampus (P < 0.01– 0.001), while Western blot analyses showed inhibition of the EGFR/NF-κB signaling pathway.
Conclusion: This study found that AS-IV improved cognitive function in diabetic db/db mice by reducing the buildup of Aβ and tau proteins in the hippocampus via the TNF-α-activated EGFR/NF-κB pathway.
Keywords: astragaloside IV, diabetic cognitive impairment, β-amyloid, tau protein, in vivo, PET-CT