Eumelanin from the skin of farm-raised giant salamanders promotes coagulation system homeostasis: a nutritional intervention for postoperative hemorrhage

Abstract

Background Postoperative hemorrhage is a serious problem that impacts patient recovery. While current hemostatic agents are effective, they also pose a thrombosis risk. Therefore, it is critical to develop safe and natural nutritional intervention strategies. Objective This study examines the regulatory effect of eumelanin from the skin of farm-raised giant salamanders (GS) on coagulation homeostasis and assesses its potential as a dietary supplement for postoperative recovery. Methods The structure and biosafety of GS eumelanin were analyzed using SEM-EDS and FTIR, along with various other detection methods. Male Wistar rats (114) were used to evaluate coagulation function and for metabolomic analysis. We assessed tail bleeding parameters and coagulation indices at 2 and 24 h after treatment and analyzed intestinal metabolites 2 h after gavage. Results SEM-EDS analysis reveals that the GS eumelanin has an irregular aggregated structure with Ca 2+ involved in its formation. Multi-technique characterization (UV–Vis, FTIR, and XPS) confirmed the material as eumelanin, with characteristic optical absorption, surface functional groups, and elemental composition. Untargeted and targeted metabolomic analyses revealed that tranexamic acid and aminocaproic acid were detected in the intestinal metabolites of GS eumelanin. It also increases the levels of several other amino acids, including lysine, aspartic acid, and arginine, as well as the Ca 2+ release. At 2 h post-gavage, the H-GS eumelanin group showed a 38.2% reduction in hemorrhage volume and a 27.0% reduction in hemostasis time compared with the CON group ( p < 0.01). At the same time point, PT was 15.8 ± 1.0 s in H-GS eumelanin, compared to 17.3 ± 1.1 s in CON ( p < 0.01). FIB was 230 ± 10 mg/dL in H-GS eumelanin versus 178 ± 7 mg/dL in CON ( p < 0.001). Both values remained within the rat physiological ranges: 13.32–17.37 s for PT and 180–504 mg/dL for FIB. This indicates a favorable hemostatic safety profile, without any evidence of hypercoagulability. Conclusion This study reveals that GS eumelanin regulates coagulation homeostasis through its nanostructure and intestinal metabolites. Our results provide a nutritional basis for using natural eumelanin as a functional food ingredient to help manage the risk of postoperative bleeding.