Agnuside against spatial learning and memory deficits in a mouse model of vascular dementia

Abstract

Objective: Vascular dementia is the second most common cause of cognitive impairment in older adults, yet effective pharmacological treatments remain limited. Agnuside, a naturally occurring compound with antioxidant and anti-inflammatory properties, has shown vascular-protective potential; however, its role in vascular dementia remains unclear.

Methods: A mouse model of permanent bilateral common carotid artery occlusion was established to evaluate the effects of Agnuside. Cognitive function was assessed using the Morris water maze. Cerebral blood flow, tissue injury, and hippocampal cornu ammonis 1 neuronal apoptosis were evaluated using laser speckle imaging, triphenyltetrazolium chloride staining, Nissl staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Transcriptomic and pathway enrichment analyses were performed, and key targets were validated using quantitative real-time polymerase chain reaction and Western blotting.

Results: Agnuside improved spatial learning and memory, increased cerebral blood flow, reduced histopathological damage, and decreased neuronal apoptosis. Angiogenesis-related genes (Mmp3, IL1RN, and ALAS2) were differentially expressed, and selected genes were validated using quantitative real-time polymerase chain reaction. The PI3K-AKT and MAPK pathways were significantly enriched, and Agnuside restored AKT and ERK1/2 phosphorylation.

Conclusions: Agnuside exerts neurovascular protective effects in mice with vascular dementia, likely through modulation of angiogenesis-related genes and activation of AKT/ERK signaling. These findings provide evidence that Agnuside serves as a potential therapeutic candidate for vascular dementia.

Mutating ubiquitin carboxy terminal hydrolase L1 cysteine 152 ameliorates white matter injury and functional deficits in experimental vascular dementia
Zhiping Mi, Dennis J. Zeh, Jie Ma +7
Scientific Reports7 Oct 2026Peer-reviewedCC BY-NC-ND 4.0Full textNeurologyCrossref
Frontal Cerebral Blood Flow Deficits in Behavioral Variant Frontotemporal Dementia: Associations With Clinical Symptoms, Peripheral Vascular Biomarkers, and Neuroimaging Measures.
Jiahui Hou, Qianqian He, Xiuxia Fu +5
CNS neuroscience & therapeutics1 Nov 2026Peer-reviewedCC BYFull textPsychiatry & mental healthEurope PMCPMC
Cardio-pulmonary vascular deficits and progression to overt ischemic syndromes in ambulant long-COVID population
Narendran Gopalan, Prabhu Ethiraj, Guruprasad Sogunuru +25
Scientific Reports6 Oct 2026Peer-reviewedCC BY-NC-ND 4.0Full textNeurologyCrossref
Shared and Divergent Multisensory Emotion Perception Deficits across Mild Cognitive Impairment, Alzheimer’s Disease, and Frontotemporal Dementia: A Systematic Review and Hierarchical Bayesian Meta-Analysis
Yi Lin, Yangfan Lu, Enze Tang +1
PsyArXiv1 Oct 2026PreprintCC BY 4.0Full textPsychiatry & mental healthOSF
Motor Deficits in a Mouse Model of Frontotemporal Dementia: Cortical Tau Pathology and Reduced Nigrostriatal Dopaminergic Markers
Maciej Zadrożny, Patrycja Zadrożna, Wiktor Niewiadomski +5
Cells20 Oct 2026Peer-reviewedCC BY 4.0Full textPhysiologyCrossrefEurope PMC

Cite

BibTeX RIS

BibTeX

@article{li2026agnuside,
  title = {{Agnuside against spatial learning and memory deficits in a mouse model of vascular dementia}},
  author = {Shao-fa Li and Hui-min Wei and Jin-yong Teng and Xiao-qin Huang and Zai-zhi Yang and Ju-fang Chen and Yu-ji Huang and Ying Wu},
  journal = {The Journal of International Medical Research},
  year = {2026},
  month = sep,
  doi = {10.1177/03000605261483194},
  url = {https://doi.org/10.1177/03000605261483194},
  note = {CC BY-NC 4.0},
}

RIS

TY  - JOUR
TI  - Agnuside against spatial learning and memory deficits in a mouse model of vascular dementia
AU  - Shao-fa Li
AU  - Hui-min Wei
AU  - Jin-yong Teng
AU  - Xiao-qin Huang
AU  - Zai-zhi Yang
AU  - Ju-fang Chen
AU  - Yu-ji Huang
AU  - Ying Wu
PY  - 2026
DA  - 2026/09/29
JO  - The Journal of International Medical Research
DO  - 10.1177/03000605261483194
UR  - https://doi.org/10.1177/03000605261483194
AB  - Objective: Vascular dementia is the second most common cause of cognitive impairment in older adults, yet effective pharmacological treatments remain limited. Agnuside, a naturally occurring compound with antioxidant and anti-inflammatory properties, has shown vascular-protective potential; however, its role in vascular dementia remains unclear.  Methods: A mouse model of permanent bilateral common carotid artery occlusion was established to evaluate the effects of Agnuside. Cognitive function was assessed using the Morris water maze. Cerebral blood flow, tissue injury, and hippocampal cornu ammonis 1 neuronal apoptosis were evaluated using laser speckle imaging, triphenyltetrazolium chloride staining, Nissl staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Transcriptomic and pathway enrichment analyses were performed, and key targets were validated using quantitative real-time polymerase chain reaction and Western blotting.  Results: Agnuside improved spatial learning and memory, increased cerebral blood flow, reduced histopathological damage, and decreased neuronal apoptosis. Angiogenesis-related genes (Mmp3, IL1RN, and ALAS2) were differentially expressed, and selected genes were validated using quantitative real-time polymerase chain reaction. The PI3K-AKT and MAPK pathways were significantly enriched, and Agnuside restored AKT and ERK1/2 phosphorylation.  Conclusions: Agnuside exerts neurovascular protective effects in mice with vascular dementia, likely through modulation of angiogenesis-related genes and activation of AKT/ERK signaling. These findings provide evidence that Agnuside serves as a potential therapeutic candidate for vascular dementia.
SN  - 0300-0605
SN  - 1473-2300
ER  -

Abstract

Related

Cite