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

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.