Abstract
BackgroundHepatic 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.MethodsBALB/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.ResultsXCH 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.ConclusionsThese results demonstrated that the hepatic protective effects of Xiaochaihu decoction were mediated by HSP47/TGF-β axis.
Highlights
Hepatic fibrosis caused by chronic infection with Schistosoma japonica remains a serious public health problem in the world
Xiaochaihu decoction (XCH) alleviated liver granuloma and fibrosis in mice caused by S. japonicum Schistosoma japonicum infection caused destruction of the histological structure of mouse liver with a large number of S. japonicum eggs present around the portal veins (Fig. 1a, b)
XCH improved hepatic dysfunction and fibrosis caused by S. japonicum Schistosoma japonicum infection resulted in a drastic increase in serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) as well as hyaluronic acid (HA) and N-terminal propeptide of collagen III (PIIINP) levels and decreases of albumin (ALB) and globulin (GLOB) levels (Table 1)
Summary
Hepatic fibrosis caused by chronic infection with Schistosoma japonica remains a serious public health problem in the world. Schistosomiasis is highly debilitating with three distinct phases of clinical disease progression: acute infection; established active infection; and late chronic infection [2, 3]. Chronic and advanced schistosomiasis remain a serious public health problem in China. Schistosoma japonicum eggs cause granulomatous inflammation in the host liver during the acute phase and lead to chronic liver damage, which might progress. Liver cirrhosis is the advanced stage of fibrosis due to chronic inflammation [8]. Macrophage-produced TGF-β1 activates otherwise quiescent hepatic stellate cells which in turn secrete an extracellular matrix, leading to fibrosis [8, 11]
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