WITHDRAWN: Salvigenin promotes survival rate in Caecal ligation puncture induced sepsis rat model by regulating IL-17 pathway and Syk inhibition.

Sepsis is a systemic infection, associates' inflammation and multiple organ dysfunction. Patients suffering from sepsis has higher mortality rate and management of sepsis is still a challenge. Thus, given report evaluates the protective effect of salvigenin against sepsis. Caecal ligation puncture (CLP) method was used to induce sepsis in rats, grouped into four different groups such as Sham, CLP, Salvigenin 25 and 50 mg/kg group treated with salvigenin 25 and 50 mg/kg i.p. after the induction of sepsis for the duration of 7 days. Survival rate, oxidative stress parameters and inflammatory cytokines were estimated in salvigenin treated sepsis rats. Moreover, effect of salvigenin was estimated on vascular permeability, infiltration of neutrophil and mRNA expression of spleen tyrosine kinase (Syk) in sepsis rat. Histopathology of lung and spleen tissue were observed by Hematoxylin and Eosin (H&E) staining. Moreover, network pharmacology and docking study were performed on the assessment of molecular interaction of salvigenin in sepsis. Result of investigation shows that salvigenin improves the survival rate, reduces oxidative stress parameters and inflammatory cytokines than CLP group of rats. There was significant reduction in vascular permeability and infiltration of neutrophil in salvigenin treated group than CLP group of rats. Organ weight, percentage of water content in lung and lung injury score was reduced in salvigenin treated group than CLP group of rats. Treatment with salvigenin attenuates the altered expression of IL-17 and Syk proteins in the lung tissue of sepsis rats. Data of network pharmacology suggest that salvigenin interact with IL-17 and Syk targets of inflammatory pathway in sepsis and salvigenin interact with Syk protein with a binding strength of -7.1 Kcal/mol. In conclusion, salvigenin improves survival rate in CLP induced sepsis rats by reducing oxidative stress and inflammatory cytokines. Salvigenin promotes the immune cell function by inhibiting the expression of Syk.