Genistein improves schistosomiasis liver granuloma and fibrosis via dampening NF-kB signaling in mice.
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.
Department of Microbiology and Immunology, Medical College, China Three Gorges University, Yichang, Hubei, 443002, China.|Jiangxi Key Laboratory for Postharvest Technology and Nondestructive Testing of Fruits and Vegetables, College of Agronomy, Jiangxi Agricultural University, Nanchang, Jiangxi, 330045, China.
Chunpeng
C
Wan
Department of Microbiology and Immunology, Medical College, China Three Gorges University, Yichang, Hubei, 443002, China.
Fen
F
Jin
Department of Microbiology and Immunology, Medical College, China Three Gorges University, Yichang, Hubei, 443002, China.
Youqin
Y
Du
Department of Microbiology and Immunology, Medical College, China Three Gorges University, Yichang, Hubei, 443002, China.
Kang
K
Yang
Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330006, People's Republic of China.
Liangliang
L
Yao
Department of Microbiology and Immunology, Medical College, China Three Gorges University, Yichang, Hubei, 443002, China. meizhigang@ctgu.edu.cn.
Zhigang
Z
Mei
Department of Microbiology and Immunology, Medical College, China Three Gorges University, Yichang, Hubei, 443002, China. huangweifeng@ctgu.edu.cn.
Weifeng
http://orcid.org/0000-0001-8546-1591
W
Huang
D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D058487:Cercaria / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D004789:Enzyme Activation; D019833:Genistein / Q000627:therapeutic use*; D006099:Granuloma / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000469:parasitology / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D012549:Schistosoma japonicum / Q000187:drug effects* / Q000235:genetics; D012554:Schistosomiasis japonica / Q000188:drug therapy* / Q000469:parasitology; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000981:Antiprotozoal Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C556062:IL10 protein, mouse; D012333:RNA, Messenger; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019833:Genistein; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase
Genistein; Liver fibrosis; Liver granuloma; Schistosomiasis