Hydroxysafflor Yellow A modulation of metabolite networks and inhibition of JAK2/STAT1 pathway in sepsis.

Abstract

Sepsis, a severe infectious disease causing multiple organ dysfunction, requires further exploration of its pathomechanisms and therapeutic options. Hydroxysafflor Yellow A (HYSA), extracted from Carthamus tinctorius L, has shown anti-inflammatory and antioxidant properties effective in treating sepsis, though its precise mechanism remains unclear. In this study, a cecum ligation puncture (CLP) model was used to evaluate HYSA's effects on sepsis-induced organ injury. HYSA (300 mg/kg) was administered intraperitoneally 4 h post-CLP. Results showed that HYSA inhibited the inflammatory response and improved pathological scores in the liver, lungs, and kidneys. Metabolomics analysis identified key metabolites and pathways influenced by HYSA, including nicotinate and nicotinamide metabolism and glycine/serine metabolism. Network pharmacology and molecular docking identified JAK2/STAT1 as potential targets, with Western blotting confirmed that HYSA inhibits JAK2/STAT1 phosphorylation. These findings suggest that HYSA protects against sepsis-induced organ injury by regulating metabolic networks and modulating the JAK2/STAT1 pathway.