title: Xia-yu-xue decoction (XYXD) reduces carbon tetrachloride (CCl4)-induced liver fibrosis through inhibition hepatic stellate cell activation by targeting NF-κB and TGF-β1 signaling pathways.
abstract: BACKGROUND
  Hepatic stellate cell (HSC) activation is activated mainly by endotoxin and transforming growth factor (TGF-β1) in chronic liver injury, consequently, can be important therapeutic targets. Xia-yu-xue decoction (XYXD), a classical recipe used in China to treat liver fibrosis, and has been revealed to inhibit hepatic fibrosis in animal models, the mechanism of action of XYXD remains elusive. In the present study, we evaluated whether XYXD reduced endotoxin and pro-fibrogenic pathways induced by lipopolysaccharide (LPS) and TGF-β1 in HSCs.
  
  
  METHODS
  The in vivo effect of XYXD on fibrosis progression was assessed in mice model induced by carbon tetrachloride (CCl4), The in vitro effect of XYXD on mice GFP-Col-HSC cells was evaluated using LPS and TGF-β1 stimulation.
  
  
  RESULTS
  XYXD treatment reduced CCl4-induced liver fibrosis and decreased hepatic hydroxyproline (Hyp) content, the mRNA levels of smooth muscle actin (α-SMA) and Col 1(α1) in fibrotic liver. XYXD suppressed nuclear factor-κB (NF-κB) activation induced by LPS and TGF-β1 assessed by using NF-κB-luciferase reporter. The expression of NF-κB target genes, chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 2 (CXCL2) induced by LPS was suppressed after XYXD treatment. The expression of TGF-β1 targets genes, Col1(α1) and tissue inhibitor of metalloproteinases (TIMP1) induced by TGF-β1 was inhibit after XYXD treatment.
  
  
  CONCLUSIONS
  XYXD treatment attenuates liver fibrosis by inhibiting HSC activation via inhibition of NF-κB and TGF-β1 signaling pathway, thereby blocking the synthesis of Col1 (α1) and TIMP-1. These findings from present study suggest that XYXD may be a therapeutic decoction for liver fibrosis in which NF-κB and TGF-β1 are thought to take part.
authors.affiliation: Experimental Research Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. liucheng0082010@163.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. xiaxia06220509@126.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Infectious Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. 285967304@qq.com.
authors.forename: Le
authors.initials: L
authors.lastname: Tao
authors.affiliation: Experimental Research Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. czan0907@126.com.
authors.forename: Zhuoan
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Experimental Research Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. daixiuqin1989@163.com.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Pathology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. shengxia021@hotmail.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Infectious Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. dongying11@citiz.net.
authors.forename: Dongying
authors.initials: D
authors.lastname: Xue
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride