Xiaochaihu decorction relieves liver fibrosis caused by Schistosoma japonicum infection via the HSP47/TGF-β pathway

Abstract

Background Hepatic fibrosis caused by chronic infection with Schistosoma japonica remains a serious public health problem in the world. Symptoms include inflammation, liver granuloma and fibrosis, whilst treatment options are still limited. This study aims to investigate whether and how traditional Chinese medicine Xiaochaihu decoction (XCH) could mitigate liver fibrosis caused by S. japonicum infection. Methods BALB/c mice were infected with S. japonicum cercariae and treated with XCH for 16 weeks. Liver pathological changes were assessed by H&E and Masson staining. NIH3T3 and Raw264.7 cells were treated with S. japonicum egg antigens with or without XCH treatment. Quantitative real-time PCR, western blot, immunfluorescence and ELISA were performed to determine the changes of levels of fibrogenic markers. Results XCH protected mouse liver from injuries and fibrosis caused by S. japonicum infection and considerably reduced egg burden in a dose-dependent manner. Infection with S. japonicum caused elevation of serum ALT, AST, ALP, HA and PIIINP levels and reduction of ALB and GLOB levels, which was markedly suppressed by XCH. The upregulation of TGF-β1, Hsp47, α-SMA, Col1A1 and Col3A1 in S. japonicum-infected mouse liver was also significantly inhibited by XCH. Schistosoma japonicum egg antigens promoted the expression of Hsp47, TGF-β1, Timp-1, α-SMA, Col1A1 and Col3A1 in NIH3T3 cells, and TGF-β1, CTGF, IL-13, IL-17 and IL-6 in Raw264.7 cells, which was inhibited by XCH, LY2157299 and shRNA-Hsp47. Conclusions These results demonstrated that the hepatic protective effects of Xiaochaihu decoction were mediated by HSP47/TGF-β axis.

Effect of Short-Term Tacrolimus Exposure on Rat Liver: An Insight into Serum Antioxidant Status, Liver Lipid Peroxidation, and Inflammation

“…Cytokines IL-10 and IL-13 are considered as anti-inflammatory and upregulated in acute liver injury and liver fibrosis to prevent the damage [ 23 , 45 , 46 ]. Song et al have reported that using sirolimus as an immunosuppressive drug resulted in increased level of IL-10 in liver transplant patients by affecting B cell regulatory cells [ 47 ].…”

“…Likewise, the cytokine profile is altered following liver injury. Proinflammatory cytokines, interleukin- (IL-) 10, and IL-13 exhibit an increased expression in rat liver injury to protect the tissue from damage [ 23 ]. A role of IL-10 has been previously described owing to progression of liver inflammation and oxidative stress-related liver injury.…”

Analysis of Intestinal Microflora and Metabolites From Mice With DSS-Induced IBD Treated With Schistosoma Soluble Egg Antigen

“…Although the pathogenesis of IBD remains to be further explored, most studies believe that IBD is related to immune imbalance ( Nanini et al, 2018 ; Neurath, 2019 ; Mitsialis et al, 2020 ). As a common chronic parasitic worm ( Huang et al, 2016a ; Huang et al, 2016b ; Deol et al, 2019 ), a schistosome develops a variety of mechanisms to manipulate the adaptive immune system of the host while infecting the host ( Huang et al, 2016a ; Huang et al, 2019 ; Huang et al, 2020a ; Huang et al, 2020b ; Buck et al, 2020 ; Zheng et al, 2020 ). Studies have shown that the host immune system gradually shifts from its own invasive T helper 1 (Th1) cell response to anti-inflammatory Th2 cell response 4–6 weeks after cercariae penetrated the skin of the host ( Dunne and Cooke, 2005 ).…”

Research on predicting the occurrence of hepatocellular carcinoma based on Notch signal-related genes using machine learning algorithms

“…The correlation analysis of our presented study also con rmed the signi cant positive correlation between LAMA4, RAD51 and TYMS and Macrophages M0. It has been reported that TGF-β1 is strongly positively correlated with macrophage in HCC [34]. Macrophages M0 can secrete a large amount of TGF-β1 [34].…”