Anticoagulant peptide LR from Whitmania pigra ameliorates cerebral ischemia-reperfusion injury.

Abstract

BACKGROUND: Ischemic stroke (IS) is a leading cause of death and disability worldwide. Hypercoagulability and thrombus formation play critical roles in its pathogenesis. Leech-derived peptides, especially those obtained from Whitmania pigra, have demonstrated potential antithrombotic and neuroprotective effects. This study aimed to investigate the therapeutic efficacy and underlying mechanisms of a leech peptide in a rat model of cerebral ischemia/reperfusion injury. METHODS: Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion followed by reperfusion to establish the IS model. Rats received low-dose or high-dose leech peptide, edaravone as a positive control, or saline. Behavioral assessments, infarct volume measurement, laser speckle imaging for cerebral perfusion, and histopathology were performed. Hemorheology and coagulation parameters were analyzed. Additionally, thrombin levels and fibrinolytic factors were evaluated using ELISA. Biosafety was assessed through hemolysis and histological evaluation of major organs. RESULTS: Leech peptide significantly reduced infarct volume, improved neurological scores, enhanced cerebral perfusion, and preserved brain tissue structure. It modulated thrombin-related parameters, ameliorated coagulation dysfunction, and modulated fibrinolysis-associated factors, thereby contributing to the restoration of coagulation-fibrinolysis homeostasis. Low-dose treatment showed comparable or superior efficacy to the high dose with better safety. No significant toxicity or hemolysis was observed. CONCLUSIONS: Leech peptide derived from Whitmania pigra exerts neuroprotective effects in cerebral ischemia/reperfusion injury through anticoagulation and thrombolysis. These findings support its potential as a novel candidate for IS therapy. TRIAL REGISTRATION: Not applicable. This study did not involve human participants.