Bromelain Alleviates Sleep Deprivation-Induced Intestinal Injury via TRPA1/5-HT Axis

  • J Agric Food Chem. 2025 Jul 23;73(29):18153-18164. doi: 10.1021/acs.jafc.5c02446.
Hai-Yi Zhang  1  2  3 ,  Yan Li  1  2  3 ,  Wen-Hao Wang  1  2  3 ,  Yao Deng  1  2  3 ,  Si-Ying Chen  1  2  3 ,  Zi-Jian Zheng  1  2  3 ,  Hao Ren  1  2  3 ,  Jian Sun  1  2  3
Affiliations
  • 1. State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China.
  • 2. Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, China.
  • 3. National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
PMID: 40662381 DOI: 10.1021/acs.jafc.5c02446
Abstract

Sleep deprivation (SD) significantly disrupts intestinal homeostasis and causes intestinal damage. Previous research conducted by our group has demonstrated that SD induces intestinal damage through intestinal hypoxia. Intestinal hypoxia is closely associated with ischemia. In this study, we found that bromelain (BR), a compound with anticoagulant and anti-inflammatory properties, mitigated SD-induced intestinal damage, and restored blood perfusion and clotting function. Mechanistically, we identified 5-HT as a key mediator during SD, and BR reduced 5-HT levels by inhibiting TRPA1-mediated calcium influx in Enterochromaffin (EC) cells. These findings define the TRPA1-5-HT axis as a novel therapeutic target for sleep disorder-related gastrointestinal pathologies and mechanistically expand BR's therapeutic potential from anticoagulation to direct modulation of 5-HT via calcium-dependent inhibition of TRPA1.

Keywords
5-HT; TRPA1; bromelain; enterochromaffin cells; intestinal barrier; sleep deprivation.
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