Sepsis is associated with exacerbated inflammatory response which subsequently results in multiple organ dysfunction. Sepsis accounts for high mortality and morbidity among newborns worldwide. Narciclasine is a plant alkaloid which has shown to possess anti-inflammatory properties. In this study we investigated the effect and mechanism of action of narciclasine in neonatal sepsis rat models. The excessive release of S100A8/A9 or calprotectin in neonatal sepsis could be detrimental as it could exacerbate the inflammatory responses. We found that narciclasine significantly reduced the plasma levels of S100A8/A9 and also suppressed its expression in the liver and lung. The systemic and local bacterial load was also reduced in the narciclasine treated rats. The systemic and local production of pro-inflammatory cytokines in plasma and organs (liver and lungs) was significantly reduced in the narciclasine treated rats. The histopathological studies showed that narciclasine prevents the organ damage associated with sepsis and improved the survival of neonatal rats. Sepsis increased the phosphorylated NF-κβ p65 protein expression in the liver. Narciclasine suppressed the phosphorylation of nf-κβ p65 and the degradation of NF-κβ inhibitory protein alpha. It could also suppress the expression of adaptor proteins of the toll like receptor signaling pathway viz., myeloid differentiation factor 88 (MyD88), Interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor associated factor 6 (TRAF6). These results suggest that narciclasine protects against sepsis in neonatal rats through the inhibition of calprotectin, pro-inflammatory cytokines and suppression of NF-κβ signaling pathway.Infection is the most important cause of morbidity and mortality in intensive care units worldwide. As the immune response to infection during the neonatal period is mostly immature it is characterized by high rates of morbidity and mortality 1-3 . Most adults are usually able to restrict the bacterial infection whereas neonates are not able to restrict the bacterial infection and develop a severe systemic inflammatory response. Sepsis is a life threatening health condition which occurs due to the severe and systemic inflammatory response to infection. This syndrome starts with dysregulated inflammation, systemic inflammatory response syndrome (SIRS) progressing to severe sepsis and septic shock 4 . It is the most common cause of death in critically ill patients in non-coronary intensive care units 5 .Despite the advancement of medical care, sepsis is one of the leading causes of morbidity and mortality among babies in the neonatal intensive care units 6 . This is mainly due to the non-specific signs and symptoms of neonatal sepsis 2 . Antibiotics and supportive care are the mainstay of treatment at present. The nosocomial pathogens are increasingly becoming resistant to the antimicrobials currently being used. Thus alternative therapeutic options such as anti-inflammatory drugs could be beneficial as neonatal sepsis is characterized by elev...

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