Investigation Into the Inhibition of Ferroptosis by Praeruptorin-A in Sepsis Based on Network Pharmacology

Praeruptorin A (PA), a monomer derived from the traditional Chinese medicine Peucedani Radix, is known for its therapeutic properties, including heat clearance, phlegm dissolution, and asthma relief. Sepsis, characterized as a systemic inflammatory response syndrome (SIRS), is triggered by a cytokine storm resulting from pathogenic Infection and can progress to multi-organ failure. This study investigates and predicts the effective molecular targets and potential mechanisms of PA in the context of sepsis through the application of network pharmacology. The identified targets were subsequently validated using an in vitro molecular model, thereby providing a robust theoretical basis for our findings. Our results indicate that PA significantly reduced malondialdehyde (MDA) accumulation, ameliorated glutathione (GSH) depletion, enhanced Glutathione Peroxidase 4 (GPX4) expression, and restored mitochondrial function. Notably, PA markedly decreased prostaglandin-endoperoxide synthase 2 (PTGS2) expression, which collectively suggests that PA may inhibit Ferroptosis. We propose that PA may exert its inhibitory effects on Ferroptosis in macrophages via modulation of PTGS2, highlighting its potential as a drug for sepsis treatment.

PTGS2; Praeruptorin A; ferroptosis; sepsis.