Therapeutic potential of hydrogen-rich water in zebrafish model of Alzheimer's disease: targeting oxidative stress, inflammation, and the gut-brain axis

Jiaxuan He; Peiye Xu; Ting Xu; Haiyang Yu; Lei Wang; Rongbing Chen; Kun Zhang; Yueliang Yao; Yanyan Xie; Qinsi Yang; Wei Wu; Da Sun; Dejun Wu

doi:10.3389/fnagi.2024.1515092

Therapeutic potential of hydrogen-rich water in zebrafish model of Alzheimer's disease: targeting oxidative stress, inflammation, and the gut-brain axis

Front Aging Neurosci. 2025 Jan 7:16:1515092. doi: 10.3389/fnagi.2024.1515092. eCollection 2024.

Authors

Jiaxuan He^#¹, Peiye Xu^#¹, Ting Xu^#¹, Haiyang Yu¹, Lei Wang², Rongbing Chen³, Kun Zhang⁴, Yueliang Yao⁵, Yanyan Xie⁶, Qinsi Yang⁷, Wei Wu⁸, Da Sun¹, Dejun Wu⁹

Affiliations

¹ Institute of Life Sciences and Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China.
² Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, China.
³ Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
⁴ Chongqing Municipality Clinical Research Center for Geriatric Diseases, Chongqing University Three Gorges Hospital, Chongqing, China.
⁵ Fuzhou Innovation Center for AI Drug, Fuzhou Medical College of Nanchang University, Fuzhou, China.
⁶ The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou, China.
⁷ Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China.
⁸ Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College, Chongqing University, Chongqing, China.
⁹ Department of Geriatric Medicine, Quzhou People's Hospital, Quzhou, China.

^# Contributed equally.

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder, with amyloid-beta (Aβ) aggregation playing a key role in its pathogenesis. Aβ-induced oxidative stress leads to neuronal damage, mitochondrial dysfunction, and apoptosis, making antioxidative strategies promising for AD treatment. This study investigates the effects of hydrogen-rich water (HRW) in a zebrafish AD model. Zebrafish were exposed to aluminum chloride to induce AD-like pathology and then treated with HRW using a nanobubble device. Behavioral assays, ELISA, Hematoxylin-eosin (H&E) staining, and reactive oxygen species (ROS) and neutrophil fluorescence labeling were employed to assess HRW's impact. Additionally, 16S rRNA sequencing analyzed HRW's effect on gut microbiota. HRW can significantly improve cognitive impairment and depression-like behavior in zebrafish AD model, reduce Aβ deposition (p < 0.0001), regulate liver Soluble epoxide hydrolase (sEH) levels (p < 0.05), reduce neuroinflammation, and reduce oxidative stress. Furthermore, HRW reduced the number of harmful bacteria linked to AD pathology by restoring the balance of microbiota in the gut. These findings suggest that HRW has potential as a therapeutic strategy for AD by targeting oxidative stress, inflammation, and gut-brain axis modulation.

Keywords: Alzheimer’s disease; alleviated neuroinflammation and oxidative stress; antioxidant; behavior; hydrogen-rich water; modulated liver sEH activity; reduced Aβ deposition; zebrafish.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was funded by The Science and Technology Research Project of the Jiangxi Provincial Department of Education (GJJ218110), the Graduate Scientific Research Foundation of Wenzhou University (3162024004102 and 3162024003057).