Genistein improves schistosomiasis liver granuloma and fibrosis via dampening NF-kB signaling in mice
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In schistosomiasis, egg deposition in the liver contributes to the formation of hepatic granuloma and fibrosis, which are the most serious clinical pathological features. It has been proposed that activation of the nuclear factor kappa B (NF-κB) signaling pathways is closely associated with the development of hepatic granuloma and fibrosis. Genistein has been shown to inhibit the activity of NF-κB signaling pathways, which might be a potential agent to protect against Schistosoma japonicum egg-induced liver granuloma and fibrosis. In this study, liver granuloma and fibrosis were induced by infecting BALB/c mice with 18 ± 3 cercariae of S. japonicum. At the beginning of egg granuloma formation (early phase genistein treatment from 4 to 6 weeks after infection) or after the formation of liver fibrosis (late phase genistein treatment from 6 to 10 weeks after infection), the infected mice were injected with genistein (25, 50 mg/kg). The results revealed that genistein treatment significantly decreased the extent of hepatic granuloma and fibrosis in infected mice. The activity of NF-κB signaling declined sharply after the treatment with genistein, as evidenced by the inhibition of NF-κB-p65, phospho-NF-κB-p65, and phospo-IκB-α expressions, as well as the expression of IκB-α and the messenger RNA (mRNA) expression of inflammatory cytokines (MCP1, TNFα, IL1β, IL4, IL10) mediated by NF-κB signaling pathways in the early phase of the infection. Moreover, western blot and immunohistochemistry assays demonstrated that the contents of α-smooth muscle actin (α-SMA) and transforming growth factor-β were dramatically reduced in liver tissue under the treatment of genistein in the late phase of the infection. At the same time, the mRNA expression of MCP1, TNFα, and IL10 was inhibited markedly. These results provided evidence that genistein reduces S. japonicum egg-induced liver granuloma and fibrosis, at least partly due to decreased NF-κB signaling, and subsequently decreased MCP1, TNFα, and IL10 expressions. This implies that genistein can be a potential natural agent against schistosomiasis.
KeywordsGenistein Schistosomiasis Liver granuloma Liver fibrosis
The authors would like to thank the Animal Research Center of China Three Gorges University staff for their technical support. Additionally, we would like to acknowledge the invaluable technical assistance provided by Lei Wang.
CW, FJ, ZM, and WH designed the study protocol; CW, FJ, KY, and LY were responsible for the conduct of the study; and KY and WH drafted the first version of the manuscript which was then substantially revised by all authors. All authors read and approved the final manuscript.
Compliance with ethical standards
Funding for this study was provided by National Natural Science Foundation of China (No. 81100281) and Hubei Province Health and Family Planning Scientific Research Project (No. WJ2015XB018).
Conflict of interest
The authors declare that they have no conflict of interest.
Availability of data and materials
The datasets supporting the conclusions of this article are included within the article.
Consent for publication
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