Oral nano-antioxidants improve sleep by restoring intestinal barrier integrity and preventing systemic inflammation

Zhanfeng Wu; Lei Liu; Lei Li; Xinran Cao; Wang Jia; Xiaodan Liao; Zhongpu Zhao; Hedong Qi; Guoqiang Fan; Huiqiang Lu; Chunying Shu; Mingming Zhen; Chunru Wang; Chunli Bai

doi:10.1093/nsr/nwad309

Oral nano-antioxidants improve sleep by restoring intestinal barrier integrity and preventing systemic inflammation

Natl Sci Rev. 2023 Dec 4;10(12):nwad309. doi: 10.1093/nsr/nwad309. eCollection 2023 Dec.

Authors

Zhanfeng Wu^{1

2}, Lei Liu^{1

2}, Lei Li^{1

2}, Xinran Cao^{1

2}, Wang Jia^{1

2}, Xiaodan Liao^{1

2}, Zhongpu Zhao^{1

2}, Hedong Qi^{1

2}, Guoqiang Fan³, Huiqiang Lu⁴, Chunying Shu^{1

2}, Mingming Zhen^{1

2}, Chunru Wang^{1

2}, Chunli Bai^{1

2}

Affiliations

¹ Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ School of Pharmacy, Wenzhou Medical University, Wenzhou 325000, China.
⁴ Center for Drug Screening and Research, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou 341000, China.

Abstract

Sleep deprivation (SD) is a severe public health threat that can cause systemic inflammation and nerve damage. Few effective and side-effect-free drugs are available to address SD. However, the bidirectional communications between the brain and gut provide new strategies for anti-SD therapeutics. Here we explored oral delivery of fullerene nano-antioxidants (FNAO) in the SD model to improve sleep by regulating abnormal intestinal barrier and systemic inflammation via the brain-gut axis. SD caused excessive reactive oxygen species (ROS) production and hyperactive inflammatory responses in the intestines of zebrafish and mouse models, leading to disturbed sleep patterns and reduced brain nerve activity. Of note, based on the property of the conjugated π bond of the C₆₀ structure to absorb unpaired electrons, oral FNAO efficiently reduced the excessive ROS in the intestines, maintained redox homeostasis and intestinal barrier integrity, and ameliorated intestinal and systemic inflammation, resulting in superior sleep improvement. Our findings suggest that maintaining intestinal homeostasis may be a promising avenue for SD-related nerve injury therapy.

Keywords: brain-gut axis; fullerene nano-antioxidants; inflammation; reactive oxygen species; sleep deprivation.