PMID- 24941000 OWN - NLM STAT- MEDLINE DCOM- 20151009 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 6 DP - 2014 TI - A boswellic acid-containing extract ameliorates schistosomiasis liver granuloma and fibrosis through regulating NF-kappaB signaling in mice. PG - e100129 LID - 10.1371/journal.pone.0100129 [doi] LID - e100129 AB - 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-kappaB signaling as evidenced by reduced IkappaB kinase (IKK) activation, the mRNA expression of VEGF (vascular endothelial growth factor, VEGF), TNF-alpha (tumor necrosis factor-alpha TNF-alpha) and MCP-1 (monocyte chemotactic protein 1, MCP-1) was decreased. Moreover, immunohistochemical analysis (IHC) revealed that the content of alpha-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-kappaB signaling and the subsequently decreased expression of VEGF, TNF-alpha, and MCP-1. Suppression of the activation of hepatic stellate cells (HSC) may also be involved in the therapeutic efficacy of BSE-CD. FAU - Liu, Miao AU - Liu M AD - Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China; Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China. FAU - Wu, Qingsi AU - Wu Q AD - Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China; Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China. FAU - Chen, Peng AU - Chen P AD - College of Clinical Medical Sciences, Anhui Medical University, Hefei, Anhui, People's Republic of China. FAU - Buchele, Berthold AU - Buchele B AD - Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, Ulm, Germany. FAU - Bian, Maohong AU - Bian M AD - Department of Blood Transfusion, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China. FAU - Dong, Shengjian AU - Dong S AD - Department of Clinical Laboratory, Hefei Second People's Hospital, Hefei, Anhui, People's Republic of China. FAU - Huang, Dake AU - Huang D AD - Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China; Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China. FAU - Ren, Cuiping AU - Ren C AD - Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China; Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China. FAU - Zhang, Yuxia AU - Zhang Y AD - Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China. FAU - Hou, Xin AU - Hou X AD - Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China; Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China. FAU - Simmet, Thomas AU - Simmet T AD - Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, Ulm, Germany. FAU - Shen, Jijia AU - Shen J AD - Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China; Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140618 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Actins) RN - 0 (Anthelmintics) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) RN - 0 (Triterpenes) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (alpha-smooth muscle actin, mouse) RN - 0 (vascular endothelial growth factor A, mouse) RN - 631-69-6 (boswellic acid) SB - IM MH - Actins/genetics/metabolism MH - Animals MH - Anthelmintics/chemistry/*pharmacology MH - Cercaria/drug effects/physiology MH - Chemokine CCL2/genetics/metabolism MH - Gene Expression Regulation MH - Granuloma/*drug therapy/genetics/parasitology/pathology MH - Hepatic Stellate Cells/drug effects/metabolism/parasitology MH - Liver/drug effects/metabolism/parasitology MH - Liver Cirrhosis/*drug therapy/genetics/parasitology/pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/*antagonists & inhibitors/genetics/metabolism MH - Parasite Egg Count MH - Plant Extracts/chemistry/*pharmacology MH - Schistosoma japonicum/drug effects/physiology MH - Schistosomiasis japonica/*drug therapy/genetics/parasitology/pathology MH - Signal Transduction MH - Triterpenes/*pharmacology MH - Tumor Necrosis Factor-alpha/genetics/metabolism MH - Vascular Endothelial Growth Factor A/genetics/metabolism PMC - PMC4062494 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/06/19 06:00 MHDA- 2015/10/10 06:00 PMCR- 2014/06/18 CRDT- 2014/06/19 06:00 PHST- 2013/12/23 00:00 [received] PHST- 2014/05/22 00:00 [accepted] PHST- 2014/06/19 06:00 [entrez] PHST- 2014/06/19 06:00 [pubmed] PHST- 2015/10/10 06:00 [medline] PHST- 2014/06/18 00:00 [pmc-release] AID - PONE-D-13-52605 [pii] AID - 10.1371/journal.pone.0100129 [doi] PST - epublish SO - PLoS One. 2014 Jun 18;9(6):e100129. doi: 10.1371/journal.pone.0100129. eCollection 2014.