In Vitro And In Vivo Mechanism Of Inhibiting Schistosomiasis-induced Liver Fibrosis By Corilagin Through IL4/IL13/STAT6 Signaling Pathways In Hepatic Alternative Activated Macrophage

Background: Schisotsimiasis-induced Liver fibrosis is a pathologic process result from Schistosoma egg granuloma which seriously threatens public health.hepatic alternative activated macrophages(M2)is considered important for the process.Corilagin has shown an extensive pharmacological efficacy,including anti-inflammatory,liver protection,anti-oxidant and anti-tumor activities.This study aims to explore inhibitory effect of post-parasiticide schistosomiasis-related hepatic fibrosis by Corilagin on IL-4/IL-13/STAT6 signaling pathway in hepatic alternative activated macrophage in vitro and in vivo.Method: The effect of Corilagin(Cor)will be investigated in interleukin(IL)-4/interleukin(IL)-13-stimulatedRAW264.7 macrophage cells and Schistosoma-infected mice which were established as cellular and animal models.And inhibitory effect was also confirmed in signal transducer and activator of transcription(STAT)6 overexpressed RAW264.7 cells based on the GV367-STAT6-EGFP lentiviral system and RAW264.7 cells which STAT6 were knock-downed with gene specific si-RNAs transfected into.A multitude of technologies including RT-PCR,Western blotting,ELISA,IF,HE and Masson staining were used to detect expression of effector molecules(STAT6/P-Stat6,SOCS1,KLF4,PPAR?,PPAR,FIZZ1,Ym1,TGF-?,CD68,CD206)of M2 pathway in the cell and liver.Results: As a result,Corilagin could prevent increases in protein level of Phospho-STAT6(P-STAT6).And level of downstream mediators suppressor of cytokine signaling(SOCS)1,Kruppel-like factor(KLF)4,peroxisome proliferator-activated receptor(PPAR)?,proliferator-activated receptor(PPAR)? both at mRNA and protein were markedly suppressedafter Corilagin treatment,and level of found in inflammatory zone(FIZZ1/Retnla),chitinase 3-like protein 3(Ym1),transforming growth factor ?(TGF-?)in serum were inhibited by Corilagin.By hematoxylin and eosin(HE)staining and Massonstaining,Pathological change and area of granulomas of the liver sections from the Corialgin group were alleviated significantly.The areas of positive cells of CD68,CD206 were significantly decreased by Corilagin stained by IF.Conclusions: Corilagin suppress the alternative activated macrophage via the inhibition of L-4/IL-13/STAT6 signaling pathway,Corilagin may act against schistosomiasis-induced liver fibrosis and provide a new therapy for schistosomiasis-induced liver fibrosis in vivo and in vitro.