Shihong Zhou,1 Dandan Chen,1 Shuwei Wang,1 Xiaolin Jiang,2,3 Jiangnan Li,2,3 Jianzheng He,2– 4 Minghui Xiu1,4 

1College of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China; 2Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and University, Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China; 3College of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China; 4Key Laboratory of Dunhuang Medicine, Ministry of Education, Lanzhou, 730000, People’s Republic of China

Correspondence: Jianzheng He, Email hejianzheng1006@163.com Minghui Xiu, Email xiuminghui87@163.com

Background: Acute hypoxia-induced sleep disorders (AHISD) frequently occur in individuals exposed to high altitudes, yet current treatment options are limited. Danggui Buxue decoction (DBD) originated from the ancient medical book “NeiWaiShangBianHuo Lun” for more than 700 years, and is widely used to treat anemic diseases in clinical, with the potential to treat AHISD.
Methods: We employed a combination of behavioral assays, transcriptomics, neurotransmitter profiling, and in-silico approaches to evaluate the effects and mechanisms of DBD.
Results: DBD supplementation significantly alleviated sleep disorders in AHISD fruit flies, restoring the sleep time and the sleep structure. Mechanistically, DBD alleviated AHISD mainly by restoring neurotransmitter balance such as Glutamine (Gln) and Glutamic acid (Glu), modulating serotonin receptors (5-HT1A/1B), and suppressing neuroinflammatory Toll and Imd pathways. In addition, resveratrol, magnolol, and caffeic acid as the main active ingredients of DBD played an important role in alleviating AHISD.
Conclusion: These findings suggest DBD as a promising candidate for mitigating AHISD through neuroprotective and anti-inflammatory mechanisms.

Keywords: Danggui Buxue decoction, acute hypoxia-induced sleep disorder, neuroprotective mechanism, active ingredients, Drosophila melanogaster