Curcumae Radix polysaccharides alleviate sepsis in rats: Isolation and characterization of an active homogeneous...

Curcumae Radix (CR), a traditional Chinese herbal medicine, has shown potential in the treatment of sepsis, yet its active substances and mechanisms of action remain unclear. In this study, CR was separated into polysaccharide and non-polysaccharide fractions. Both fractions exhibited significant anti-inflammatory and anticoagulant effects in a rat model of sepsis induced by lipopolysaccharide (LPS) and carrageenan. These effects were mediated by sphingosine kinase 1 (SPHK1) signaling pathway inhibition, which protected the vascular endothelial barrier and consequently alleviated liver and lung tissue damage and mitigated sepsis symptoms. Additionally, activity-guided isolation in an LPS-induced human umbilical vein endothelial cell (HUVEC) injury model yielded a homogeneous polysaccharide, designated as CRP1-3 with a molecular weight of 5082 kDa. A physicochemical analysis and structural characterization revealed that CRP1-3 was a glucan with a backbone composed of →4)-α-D-Glcp-(1 → linkages. CRP1-3 demonstrated significant anti-inflammatory and endothelial-protective activity. These findings established that CRP is a substantially underestimated yet critical class of active substances contributing to the anti-sepsis efficacy of CR.