2. Academic Validation
  3. Edaravone-Dexborneol slows down pathological progression and cognitive decline via inhibiting S100A9 in APPswe/PS1dE9 mice

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

  • Alzheimers Res Ther. 2025 Jun 21;17(1):139. doi: 10.1186/s13195-025-01777-9.
Rui Mao # 1,  Shu Shu # 1,  Min Sun # 1,  Jiang Chen 1,  Mengsha Hu 2,  Lei Ye 1,  Siyi Xu 3,  Junqiu Jia 4,  Wenxuan Shao 1,  Xinyu Bao 1,  Yun Xu 5 6 7 8 9 10,  Xiaolei Zhu 11 12 13 14
Affiliations

Affiliations

  • 1 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
  • 2 Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, China.
  • 3 Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, 210008, China.
  • 4 Nanjing Drum Tower Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, 210008, China.
  • 5 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China. xuyun20042001@aliyun.com.
  • 6 Jiangsu Key Laboratory for Molecular Medicine, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, 210008, China. xuyun20042001@aliyun.com.
  • 7 Nanjing Neurology Clinical Medical Center, Nanjing Gulou Hospital Brain Disease and Brain Science Center, Nanjing, 210008, China. xuyun20042001@aliyun.com.
  • 8 Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, China. xuyun20042001@aliyun.com.
  • 9 Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, 210008, China. xuyun20042001@aliyun.com.
  • 10 Nanjing Drum Tower Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, 210008, China. xuyun20042001@aliyun.com.
  • 11 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China. zhuquelee@126.com.
  • 12 Jiangsu Key Laboratory for Molecular Medicine, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, 210008, China. zhuquelee@126.com.
  • 13 Nanjing Neurology Clinical Medical Center, Nanjing Gulou Hospital Brain Disease and Brain Science Center, Nanjing, 210008, China. zhuquelee@126.com.
  • 14 Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, China. zhuquelee@126.com.
  • # Contributed equally.
PMID: 40544243 DOI: 10.1186/s13195-025-01777-9
Abstract

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.

Keywords

Alzheimer's disease; Edaravone-Dexborneol; Neuroinflammation; Oxidative stress; S100A9; β-amyloid.

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