A boswellic acid-containing extract ameliorates schistosomiasis liver granuloma and fibrosis through regulating NF-κB signaling in mice.

Abstract

Boswellic acid (BA)-containing extracts such as BSE have anti-inflammatory and immunomodulatory activity. In chronic schistosomiasis, the hepatic granuloma and fibrosis induced by egg deposition in the liver is the most serious pathological manifestations. However, little is known regarding the role of BAs in Schistosoma japonicum (S. japonicum) egg-induced liver granuloma and fibrosis. In order to investigate the effect of a water-soluble complex preparation of BSE, BSE-CD, on S. japonicum egg-induced liver pathology, liver granuloma and fibrosis were induced by infecting C57BL/6 mice with 18-22 cercariae of S. japonicum. S. japonicum cercariae infected mice were injected with BSE-CD at the onset of egg granuloma formation (early phase BSE-CD treatment after 4 weeks infection) or after the formation of liver fibrosis (late phase BSE-CD treatment after 7 weeks infection). Our data show that treatment of infected mice with BSE-CD significantly reduced both the extent of hepatic granuloma and fibrosis. Consistent with an inhibition of NF-κB signaling as evidenced by reduced IκB kinase (IKK) activation, the mRNA expression of VEGF (vascular endothelial growth factor, VEGF), TNF-α (tumor necrosis factor-alpha TNF-α) and MCP-1 (monocyte chemotactic protein 1, MCP-1) was decreased. Moreover, immunohistochemical analysis (IHC) revealed that the content of α-SMA in liver tissue of BSE-CD treated mice was dramatically decreased. Our findings suggest that BSE-CD treatment attenuates S. japonicum egg-induced hepatic granulomas and fibrosis, at least partly due to reduced NF-κB signaling and the subsequently decreased expression of VEGF, TNF-α, and MCP-1. Suppression of the activation of hepatic stellate cells (HSC) may also be involved in the therapeutic efficacy of BSE-CD.

• Authors: Miao Liu, Qingsi Wu, Peng Chen, Berthold Büchele, Maohong Bian, Shengjian Dong, Dake Huang, Cuiping Ren, Yuxia Zhang, Xin Hou, Thomas Simmet, Jijia Shen
• Journal: PloS one (PLoS One) Vol. 9 Issue 6 Pg. e100129 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24941000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Anthelmintics
• Ccl2 protein, mouse
• Chemokine CCL2
• NF-kappa B
• Plant Extracts
• Triterpenes
• Tumor Necrosis Factor-alpha
• Vascular Endothelial Growth Factor A
• alpha-smooth muscle actin, mouse
• vascular endothelial growth factor A, mouse
• boswellic acid

Topics

• Actins (genetics, metabolism)
• Animals
• Anthelmintics (chemistry, pharmacology)
• Cercaria (drug effects, physiology)
• Chemokine CCL2 (genetics, metabolism)
• Gene Expression Regulation
• Granuloma (drug therapy, genetics, parasitology, pathology)
• Hepatic Stellate Cells (drug effects, metabolism, parasitology)
• Liver (drug effects, metabolism, parasitology)
• Liver Cirrhosis (drug therapy, genetics, parasitology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (antagonists & inhibitors, genetics, metabolism)
• Parasite Egg Count
• Plant Extracts (chemistry, pharmacology)
• Schistosoma japonicum (drug effects, physiology)
• Schistosomiasis japonica (drug therapy, genetics, parasitology, pathology)
• Signal Transduction
• Triterpenes (pharmacology)
• Tumor Necrosis Factor-alpha (genetics, metabolism)
• Vascular Endothelial Growth Factor A (genetics, metabolism)