Journal Article

Edaravone-Dexborneol slows down pathological progression and cognitive decline via inhibiting S100A9 in APPswe/PS1dE9 mice

Shu, Shu, Bao, Xinyu, Zhu, Xiaolei, Xu, Yun, Xu, Siyi, Sun, Min, Hu, Mengsha, Chen, Jiang, Mao, Rui, Ye, Lei, Jia, Junqiu, Shao, Wenxuan

2025

Overview

Background Edaravone-Dexborneol (EDB) presents therapeutic effects due to its anti-inflammatory, antioxidant and anti-apoptotic properties, and has been widely used in ischemic stroke. However, the detailed efficacy and potential target of EDB in Alzheimer’s disease (AD) are still elusive. Methods Male APPswe/PS1dE9 mice were administered with EDB intraperitoneally from 3.5 to 8 months of age. The cognition of mice was assessed by behavioral tests. Synaptic alternations in the hippocampus were detected by electrophysiology and Golgi staining. β-amyloid (Aβ) pathology was mainly observed by immunofluorescence. Oxidative stress-related indicators were evaluated by dedicated kits, while quantitative PCR and ELISA were used to detect pro-inflammatory factors. Proteomics analysis further identified the potential target of EDB. Results EDB was capable of delaying the cognitive decline and ameliorating the synaptic loss in APPswe/PS1dE9 mice. In addition to the anti-inflammation and anti-oxidation effects, EDB treatment mightily ablated the Aβ plaque by promoting microglial phagocytosis. Particularly, we first discovered that EDB could directly bind to S100A9, a pathological molecule that aggravates Aβ pathology and induces oxidative stress and neuroinflammation. EDB inhibited the expression, functional threonine phosphorylation and self-assembly of S100A9. Conclusion Our results indicate that EDB can improve cognitive function and slow down AD progression, and it may serve as a potential agent for AD and other S100A9-related diseases.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Alzheimer Disease - drug therapy / Alzheimer Disease - metabolism / Alzheimer Disease - pathology / Alzheimer's disease / Animals / Antibodies / Biomarkers / Biomedical and Life Sciences / Biomedicine / Calgranulin B - metabolism / Cell culture / Cerebrospinal fluid / Cognitive Dysfunction - drug therapy / Cognitive Dysfunction - metabolism / Cognitive Dysfunction - pathology / Dementia / Development and progression / Disease Models, Animal / Disease Progression / Dosage and administration / Drug therapy / Drug therapy, Combination / Edaravone - administration & dosage / Edaravone - pharmacology / Edaravone-Dexborneol / Geriatric Psychiatry / Geriatrics/Gerontology / Hippocampus - drug effects / Hippocampus - metabolism / Hippocampus - pathology / Male / Memory / Mice / Mice, Transgenic / Neuroinflammation / Neurology / Neuroprotective agents / Neurosciences / Oxidative stress / Oxidative Stress - drug effects / Proteins / S100A9 / Software / Testing / β-amyloid