Anserine reduces mortality in experimental sepsis by preventing methylglyoxal-induced capillary leakage.

Summary

Using human observational data and mechanistic models, the study shows methylglyoxal drives endothelial barrier failure and early mortality in sepsis, and that the dipeptide anserine reverses these effects. Anserine reduced capillary leak and improved survival in vivo through RAGE–MAPK pathway modulation and suppression of junctional disruption.

Key Findings

• Methylglyoxal independently associated with higher 48-hour mortality and increased catecholamine/fluid needs after sepsis onset.
• Carbonyl stress disrupted endothelial junctional proteins via RAGE–MAPK signaling, producing capillary leak.
• Anserine reduced AGE formation, preserved junctional complexes in vitro, and decreased capillary leak and mortality in vivo.

Clinical Implications

Methylglyoxal could be adopted for early risk stratification, and anserine merits early-phase clinical trials as an adjunct to reduce capillary leak and vasopressor/fluid requirements in septic shock.

Limitations

• Preclinical efficacy; no randomized clinical trial yet to confirm benefit in humans.
• Exact dosing, timing, and safety profile of anserine in septic patients remain to be established.

Future Directions

Prospective trials testing methylglyoxal-guided risk stratification and phase I/II studies of anserine in septic shock with endothelial leak endpoints.