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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2008, Vol. 2 Issue (2) : 154-165    https://doi.org/10.1007/s11684-008-0029-7
Paeoniflorin prevents hepatic fibrosis of by inhibiting TGF-β1 production from macrophages in mice
CHU Deyong1, LI Conglei1, SHEN Jilong1, WU Qiang2
1.Institute of Zoonoses of Anhui Medical University and the Key Laboratory of Gene Resource Utilization for Severe Diseases, Anhui Medical University; 2.Department of Pathology, Anhui Medical University
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Abstract In order to investigate the effect of paeoniflorin (PAE) on hepatic fibrosis of mice with Schistosomiasis japonica in vivo and in vitro, a model of hepatic fibrosis caused by schistosomiasis was established in mice infected with cercariae of Schistosoma japonicum. Then, PAE was orally administered before and after praziquantel treatment and both therapeutics were given simultaneously at different time points after the infection. The concentration of serum hyaluronic acid (HA) was determined by radioimmunoassay (RIA). Hepatic granuloma and fibrosis were evaluated via HE and Masson staining. The expression of ?-smooth muscle actin (?-SMA), transforming growth factor ?1 (TGF-?1) and collagen I (Col I) protein was detected by immunohistochemistry. The effect of soluble egg antigen (SEA) and PAE on the production of TGF-?1 from mouse peritoneal macrophages (PM?s) was investigated by RT-PCR, Western blotting and ELISA. The effect of TGF-?1 in optimum macrophage-conditioned medium (OPMCM) on the proliferation of hepatic stellate cells (HSCs) and collagen secretion from HSCs with anti-TGF-?1 antibody was explored by MTT assay and ELISA. The results show that PAE could significantly reduce the concentration of serum HA, the size of egg granuloma, the severity of hepatic fibrosis and the expression of ?-SMA, TGF-?1 and Col I protein in the pre-treatment group. However, in sim- or post-treatment group, PAE did not have any significant therapeutic effect. TGF-?1 could be secreted from PM?s stimulated by SEA. Meanwhile, the production of TGF-?1 from PM?s could be depressed significantly by PAE in a concentration-dependent manner. TGF-?1 could promote the proliferation of HSCs and the secretion of collagens. In a word, PAE can prevent hepatic granuloma and fibrosis caused by schistosomiasis japonica through the inhibition of the secretion of TGF-?1 from PM?s, the proliferation and activation of HSCs and the secretion of collagens from HSCs.
Issue Date: 05 June 2008
 Cite this article:   
LI Conglei,CHU Deyong,WU Qiang, et al. Paeoniflorin prevents hepatic fibrosis of by inhibiting TGF-β1 production from macrophages in mice[J]. Front. Med., 2008, 2(2): 154-165.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-008-0029-7
https://academic.hep.com.cn/fmd/EN/Y2008/V2/I2/154
1 Gryseels B Polman K Clerinx J Kestens L Human SchistosomiasisLancet 2006 368(9541)11061118.
doi:10.1016/S0140‐6736(06)69440‐3
2 Cioli D Pica-Mattoccia L PraziquantelParasitol Res 2003 90(Supp 1)S39
3 Southgate V R Rollinson D Tchuem Tchuente L A Hagan P Towardscontrol of Schistosomiasis in sub-Saharan AfricaJ Helminthol 2005 79(3)181185.
doi:10.1079/JOH2005307
4 Boros D L Immunopathologyof Schistosoma mansoni infectionClin MicrobiolRev 1989 2(3)250269
5 Chang D Ramalho L N Ramalho F S Martinelli A L Zucoloto S Hepatic stellate cells in humanSchistosomiasis mansoni: A comparative immunohistochemical study withliver cirrhosisActa Trop 2006 97(3)318323.
doi:10.1016/j.actatropica.2005.12.006
6 Bartley P B Ramm G A Jones M K Ruddell R G Li Y McManus D P A contributoryrole for activated hepatic stellate cells in the dynamics of Schistosomajaponicum egg-induced fibrosisInt J Parasitol 2006 36(9)9931001.
doi:10.1016/j.ijpara.2006.04.015
7 Xiong L J Zhu J F Luo D D Zen L L Cai S Q Effects of pentoxifylline on the hepaticcontent of TGF-beta1 and collagen in Schistosomiasis japonica micewith liver fibrosisWorld J Gastroenterol 2003 9(1)152154
8 Czaja M J Weiner F R Flanders K C Giambrone M A Wind R Biempica L Zern M A In vitro andin vivo association of transforming growth factor-beta 1 with hepaticfibrosisJ Cell Biol 1989 108(6)24772482.
doi:10.1083/jcb.108.6.2477
9 Matsuoka M Zhang M Y Tsukamoto H Sensitization of hepatic lipocytes by high-fat diet tostimulatory effects of Kupffer cell-derived factors: implication inalcoholic liver fibrogenesisHepatology 1990 11(2)173182.
doi:10.1002/hep.1840110204
10 Mansy S S Cellularconstituent and intercellular adhesion in Schistosoma mansoni granuloma:An ultrastructural studyJ Egypt Soc Parasitol 1998 28(1)169181
11 Wu J Zern M A Hepatic stellate cells: A targetfor the treatment of liver fibrosisJ Gastroenterol 2000 35(9)665672.
doi:10.1007/s005350070045
12 Tsuboi H Hossain K Akhand A A Takeda K Du J Rifa'i M Dai Y Hayakawa A Suzuki H Nakashima I Paeoniflorininduces apoptosis of lymphocytes through a redox-linked mechanismJ Cell Biochem 2004 93(1)162172.
doi:10.1002/jcb.20134
13 Yamahara J Yamada T Kimura H Sawada T Fujimura H Biologically active principles of crudedrugs. anti-allergic principles of “shoseiryu-to.” i.effect on delayed-type allergy reactionYakugaku Zasshi 1982 102(9)881886
14 Chen F Cai W Chen Z Chen X Liu R Dynamic changes in the collagen metabolism of liver fibrosisat the transcription level in rabbits with Schistosomiasis japonicaChin Med J (Engl) 2002 115(11)16371640
15 Nouohi T Tanaka Y Tsukada T Sato C Marumo F Appearance of alpha-smooth-muscle-actin-positivecells in hepatic fibrosisLiver 1991 11(2)100105
16 Chu D Y Luo Q L Li C L Gao Y F Yu L Wei W Wu Q Shen J L Paeoniflorininhibits TGF-beta1-mediated collagen production by Schistosoma japonicumsoluble egg antigen in vitroParasitology 2007 134(Pt 11)16111621
17 Lappalainen K Jaaskelainen I Syrjanen K Urtti A Syrjanen S Comparison of cell proliferation and toxicityassays using two cationic liposomesPharmRes 1994 11(8)11271131.
doi:10.1023/A:1018932714745
18 Vetter M Chen Z J Chang G D Che D Liu S Chang C H Cyclosporina disrupts bradykinin signaling through superoxideHypertension 2003 41(5)11361142.
doi:10.1161/01.HYP.0000068201.48340.3B
19 Lowry O H Rosebrough N J Farr A L Randall R J Protein measurementwith the folin phenol reagentJ Biol Chem 1951 193(1)265275
20 Zhang X Yu W P Gao L Wei K B Ju J L Xu J Z Effectsof lipopolysaccharides stimulated Kupffer cells on activation of rathepatic stellate cellsWorld J Gastroenterol 2004 10(4)610613
21 Kopke-Aguiar L A Martins J R Passerotti C C Toledo C F Nader H B Borges D R Serumhyaluronic acid as a comprehensive marker to assess severity of liverdisease in SchistosomiasisActa Trop 2002 84(2)117126.
doi:10.1016/S0001‐706X(02)00136‐5
22 Pearce E J MacDonald A S The immunobiology of SchistosomiasisNat Rev Immunol 2002 2(7)499511.
doi:10.1038/nri843
23 Noel W Raes G Hassanzadeh Ghassabeh G De Baetselier P Beschin A Alternatively activated macrophagesduring parasite infectionsTrends Parasitol 2004 20(3)126133.
doi:10.1016/j.pt.2004.01.004
24 Song E Ouyang N Horbelt M Antus B Wang M Exton M S Influenceof alternatively and classically activated macrophages on fibrogenicactivities of human fibroblastsCell Immunol 2000 204(1)1928.
doi:10.1006/cimm.2000.1687
25 Hesse M Modolell M La Flamme A C Schito M Fuentes J M Cheever A W Pearce E J Wynn T A Differential regulation of nitric oxide synthase-2 andarginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathologyis shaped by the pattern of l-arginine metabolismJ Immunol 2001 167(11)65336544
26 Wynn T A Il-13effector functionsAnnu Rev Immunol 2003 21425456.
doi:10.1146/annurev.immunol.21.120601.141142
27 Dooley S Delvoux B Lahme B Mangasser-Stephan K Gressner A M Modulation of transforminggrowth factor beta response and signaling during transdifferentiationof rat hepatic stellate cells to myofibroblastsHepatology 2000 31(5)10941106.
doi:10.1053/he.2000.6126
28 Otsuka M Tsuchiya S Aramaki Y Involvement of erk, a map kinase, in the production ofTGF-beta by macrophages treated with liposomes composed of phosphatidylserineBiochem Biophys Res Commun 2004 324(4)14001405.
doi:10.1016/j.bbrc.2004.09.198
29 Chen Y X Lu C H Xie W F Zhang X R Zhang Z B Wei L X Jin Y X Guo Y J Effects of ribozyme targeting platelet-derived growth factorreceptor beta subunit gene on the proliferation and apoptosis of hepaticstellate cells in vitroChin Med J (Engl) 2005 118(12)982988
30 Maher J J Interactionsbetween hepatic stellate cells and the immune systemSemin Liver Dis 2001 21(3)417426.
doi:10.1055/s‐2001‐17555
31 Verrecchia F Chu M L Mauviel A Identification of novel TGF-beta/Smad gene targets in dermalfibroblasts using a combined cDNA microarray/promoter transactivationapproachJ Biol Chem 2001 276(20)1705817062.
doi:10.1074/jbc.M100754200
32 Goumans M J Lebrin F Valdimarsdottir G Controlling the angiogenic switch: a balancebetween two distinct TGF-b receptor signaling pathwaysTrends Cardiovasc Med 2003 13(7)301307.
doi:10.1016/S1050‐1738(03)00142‐7
33 Techau M E Johansen M V Aasted B Lind P Ornbjerg N Oswald I P Cytokinemrna profiles in pigs exposed prenatally and postnatally to SchistosomajaponicumVet Res 2007 38(1)2536.
doi:10.1051/vetres:2006042
34 Farah I O Mola P W Kariuki T M Nyindo M Blanton R E King C L Repeatedexposure induces periportal fibrosis in Schistosoma mansoni-infectedbaboons: role of TGF-beta and IL-4J Immunol 2000 164(10)53375343
35 Roberts A B Sporn M B Assoian R K Smith J M Roche N S Wakefield L M Heine U I Liotta L A Falanga V Kehrl J H et al.Transforming growth factor typebeta: rapid induction of fibrosis and angiogenesis in vivo and stimulationof collagen formation in vitroProc NatlAcad Sci USA 1986 83(12)41674171.
doi:10.1073/pnas.83.12.4167
36 Varga J Rosenbloom J Jimenez S A Transforming growth factor beta (TGF Beta) causes a persistentincrease in steady-state amounts of type I and type III collagen andfibronectin mrnas in normal human dermal fibroblastsBiochem J 1987 247(3)597604
37 Kaviratne M Hesse M Leusink M Cheever A W Davies S J McKerrow J H Wakefield L M Letterio J J Wynn T A IL-13 Activatesa mechanism of tissue fibrosis that is completely TGF-beta independentJ Immunol 2004 173(6)40204029
38 Bachman K E Park B H Duel nature of TGF-beta signaling:tumor suppressor vs. tumor promoter.CurrOpin Oncol 2005 17(1)4954.
doi:10.1097/01.cco.0000143682.45316.ae
39 Purps O Lahme B Gressner A M Meindl-Beinker N M Dooley S Loss of TGF-beta dependentgrowth control during hsc transdifferentiationBiochem Biophys Res Commun 2007 353(3)841847.
doi:10.1016/j.bbrc.2006.12.125
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