Protective Effects of Calycosin Against CCl4-Induced Liver Injury with Activation of FXR and STAT3 in Mice

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• 作者：Xinli Chen (1) (2)
  Qiang Meng (1) (2)
  Changyuan Wang (1) (2)
  Qi Liu (1) (2)
  Huijun Sun (1)
  Xiaokui Huo (1) (2)
  Pengyuan Sun (1) (2)
  Xiaobo Yang (1) (2)
  Jinyong Peng (1)
  Kexin Liu (1) (2)
  
  1. Department of Clinical Pharmacology ; College of Pharmacy ; Dalian Medical University ; 9 West Section ; Lvshun South Road ; Lvshunkou District ; Dalian ; Liaoning ; 116044 ; People鈥檚 Republic of China
  2. Provincial Key Laboratory for Pharmacokinetics and Transport ; Liaoning ; Dalian Medical University ; Dalian ; Liaoning ; People鈥檚 Republic of China
  
• 关键词：acute liver injury ; bile acid metabolism ; cholesterol 7伪 ; hydroxylase ; farnesoid X receptor ; STAT3
• 刊名：Pharmaceutical Research
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：32
• 期：2
• 页码：538-548
• 全文大小：6,130 KB
• 参考文献：1. Tirkey N, Pilkhwal S, Kuhad A, Chopra K. Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney. BMC Pharmacol. 2005;5:2. CrossRef
  2. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA. 2002;287:2215鈥?0. CrossRef
  3. Thames G. Drug-induced liver injury: what you need to know. Gastroenterol Nurs. 2004;27:31鈥?. CrossRef
  4. Paine AJ. Heterogeneity of cytochrome P450 and its toxicological significance. Hum Exp Toxicol. 1995;14:1鈥?. CrossRef
  5. Williamsand AT, Burk RF. Carbon tetrachloride hepatotoxicity: an example of free radical-mediated injury. Semin Liver Dis. 1990;10:279鈥?4. CrossRef
  6. Fiorucci S, Antonelli E, Rizzo G, Renga B, Mencarelli A, Riccardi L, / et al. The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis. Gastroenterology. 2004;127:1497鈥?12. CrossRef
  7. Vaquero J, Briz O, Herraez E, Muntane J, Marin JJ. Activation of the nuclear receptor FXR enhances hepatocyte chemoprotection and liver tumor chemoresistance against genotoxic compounds. Biochim Biophys Acta. 1833;2013:2212鈥?.
  8. Meng Z, Wang Y, Wang L, Jin W, Liu N, Pan H, / et al. FXR regulates liver repair after CCl4-induced toxic injury. Mol Endocrinol. 2010;24:886鈥?7. CrossRef
  9. Chen WD, Wang YD, Zhang L, Shiah S, Wang M, Yang F, / et al. Farnesoid X receptor alleviates age-related proliferation defects in regenerating mouse livers by activating forkhead box m1b transcription. Hepatology. 2010;51:953鈥?2. CrossRef
  10. Huang W, Ma K, Zhang J, Qatanani M, Cuvillier J, Liu J, / et al. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration. Science. 2006;312:233鈥?. CrossRef
  11. Liu Y, Binz J, Numerick MJ, Dennis S, Luo G, Desai B, / et al. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis. J Clin Invest. 2003;112:1678鈥?7. CrossRef
  12. Howarth DL, Law SH, Law JM, Mondon JA, Kullman SW, Hinton DE. Exposure to the synthetic FXR agonist GW4064 causes alterations in gene expression and sublethal hepatotoxicity in eleutheroembryo medaka (Oryzias latipes). Toxicol Appl Pharmacol. 2010;243:111鈥?1. CrossRef
  13. Gao B. Cytokines, STATs and liver disease. Cell Mol Immunol. 2005;2:92鈥?00.
  14. Sleeman MW, Anderson KD, Lambert PD, Yancopoulos GD, Wiegand SJ. The ciliary neurotrophic factor and its receptor. CNTFR Alpha Pharm Acta Helv. 2000;74:265鈥?2. CrossRef
  15. Taub R. Hepatoprotection via the IL-6/Stat3 pathway. J Clin Invest. 2003;112:978鈥?0. CrossRef
  16. Hong F, Radaeva S, Pan HN, Tian Z, Veech R, Gao B. Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease. Hepatology. 2004;40:933鈥?1. CrossRef
  17. Bohm F, Kohler UA, Speicher T, Werner S. Regulation of liver regeneration by growth factors and cytokines. EMBO Mol Med. 2010;2:294鈥?05. CrossRef
  18. Demirdag K, Bahcecioglu IH, Ozercan IH, Ozden M, Yilmaz S, Kalkan A. Role of L-carnitine in the prevention of acute liver damage induced by carbon tetrachloride in rats. J Gastroenterol Hepatol. 2004;19:333鈥?. CrossRef
  19. Balunasand MJ, Kinghorn AD. Drug discovery from medicinal plants. Life Sci. 2005;78:431鈥?1. CrossRef
  20. Dong H, Lu FE, Zhao L. Chinese herbal medicine in the treatment of nonalcoholic fatty liver disease. Chin J Integr Med. 2012;18:152鈥?0. CrossRef
  21. Sun WY, Wei W, Gui SY, Wu L, Wang H. Protective effect of extract from Paeonia lactiflora and Astragalus membranaceus against liver injury induced by bacillus Calmette-Guerin and lipopolysaccharide in mice. Basic Clin Pharmacol Toxicol. 2008;103:143鈥?. CrossRef
  22. Yan F, Zhang QY, Jiao L, Han T, Zhang H, Qin LP, / et al. Synergistic hepatoprotective effect of Schisandrae lignans with Astragalus polysaccharides on chronic liver injury in rats. Phytomedicine. 2009;16:805鈥?3. CrossRef
  23. Gui SY, Wei W, Wang H, Wu L, Sun WY, Chen WB, / et al. Effects and mechanisms of crude astragalosides fraction on liver fibrosis in rats. J Ethnopharmacol. 2006;103:154鈥?. CrossRef
  24. Fan Y, Wu DZ, Gong YQ, Zhou JY, Hu ZB. Effects of calycosin on the impairment of barrier function induced by hypoxia in human umbilical vein endothelial cells. Eur J Pharmacol. 2003;481:33鈥?0. CrossRef
  25. Kovalovich K, DeAngelis RA, Li W, Furth EE, Ciliberto G, Taub R. Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice. Hepatology. 2000;31:149鈥?9. CrossRef
  26. Shomer NH, Dangler CA, Schrenzel MD, Fox JG. Helicobacter bilis-induced inflammatory bowel disease in scid mice with defined flora. Infect Immun. 1997;65:4858鈥?4.
  27. Sang Y, Yang J, Ross CR, Rowland RR, Blecha F. Molecular identification and functional expression of porcine Toll-like receptor (TLR) 3 and TLR7. Vet Immunol Immunopathol. 2008;125:162鈥?. CrossRef
  28. Asaoka K, Ikeda K, Hishinuma T, Horie-Inoue K, Takeda S, Inoue S. A retrovirus restriction factor TRIM5alpha is transcriptionally regulated by interferons. Biochem Biophys Res Commun. 2005;338:1950鈥?. CrossRef
  29. Downes M, Verdecia MA, Roecker AJ, Hughes R, Hogenesch JB, Kast-Woelbern HR, / et al. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol Cell. 2003;11:1079鈥?2. CrossRef
  30. Bleibel W, Kim S, D鈥橲ilva K, Lemmer ER. Drug-induced liver injury: review article. Dig Dis Sci. 2007;52:2463鈥?1. CrossRef
  31. Antti Zitting GS. Juha Nickels, Heikki Savolainen. acute toxic effects of trinitrotoluene on rat brain, liver and kidney: role of radical production. Arch Toxicol. 1982;51:12.
  32. Wang MY, Anderson G, Nowicki D, Jensen J. Hepatic protection by noni fruit juice against CCl(4)-induced chronic liver damage in female SD rats. Plant Foods Hum Nutr. 2008;63:141鈥?. CrossRef
  33. Seol W, Choi HS, Moore DD. An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Science. 1996;272:1336鈥?. CrossRef
  34. Thompsonand R, Strautnieks S. BSEP: function and role in progressive familial intrahepatic cholestasis. Semin Liver Dis. 2001;21:545鈥?0. CrossRef
  35. Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, / et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell. 2000;6:517鈥?6. CrossRef
  36. Ye H, Holterman AX, Yoo KW, Franks RR, Costa RH. Premature expression of the winged helix transcription factor HFH-11B in regenerating mouse liver accelerates hepatocyte entry into S phase. Mol Cell Biol. 1999;19:8570鈥?0.
  37. Brattin WJ, Glende Jr EA, Recknagel RO. Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radic Biol Med. 1985;1:27鈥?8. CrossRef
  38. Batallerand R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115:209鈥?8. CrossRef
  39. Duncan SA. Transcriptional regulation of liver development. Dev Dyn. 2000;219:131鈥?2. CrossRef
  40. Wang X, Quail E, Hung NJ, Tan Y, Ye H, Costa RH. Increased levels of forkhead box M1B transcription factor in transgenic mouse hepatocytes prevent age-related proliferation defects in regenerating liver. Proc Natl Acad Sci U S A. 2001;98:11468鈥?3. CrossRef
  41. Zachariaeand W, Nasmyth K. Whose end is destruction: cell division and the anaphase-promoting complex. Genes Dev. 1999;13:2039鈥?8. CrossRef
  42. Urizar NL, Liverman AB, Dodds DT, Silva FV, Ordentlich P, Yan Y, / et al. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science. 2002;296:1703鈥?. CrossRef
  43. Moh A, Iwamoto Y, Chai GX, Zhang SS, Kano A, Yang DD, / et al. Role of STAT3 in liver regeneration: survival, DNA synthesis, inflammatory reaction and liver mass recovery. Lab Invest. 2007;87:1018鈥?8. CrossRef
  44. Takehara T, Tatsumi T, Suzuki T, Rucker 3rd EB, Hennighausen L, Jinushi M, / et al. Hepatocyte-specific disruption of Bcl-xL leads to continuous hepatocyte apoptosis and liver fibrotic responses. Gastroenterology. 2004;127:1189鈥?7. CrossRef
  45. Jo D, Liu D, Yao S, Collins RD, Hawiger J. Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis. Nat Med. 2005;11:892鈥?. CrossRef
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Pharmacy
  Biochemistry
  Medical Law
  Biomedical Engineering
  
• 出版者：Springer Netherlands
• ISSN：1573-904X

文摘

Purpose Investigating the hepatoprotective effect of calycosin against acute liver injury in association with FXR activation and STAT3 phosphorylation. Methods The acute liver injury model was established by intraperitoneal injection of CCl4 in C57BL/6 mice. Serum alanine aminotransferase, aspartate aminotransferase, HE staining and TUNEL assay were used to identify the amelioration of the liver histopathological changes and hepatocytes apoptosis after calycosin treatment. ELISA kit and 5-bromo-2-deoxyuridine immunohistochemistry were used to measure the liver bile acid concentration and hepatocyte mitotic rate in vivo. The relation between calycosin and activation of FXR and STAT3 was comfirmed using the Luciferase assay, Molecular docking, Real-time PCR and Western Blot in vitro. Results The liver histopathological changes, hepatocytes apoptosis, liver bile acid overload and hepatocyte mitosis showed significant changes after calycosin treatment. Calycosin promoted the expression of FXR target genes such as FoxM1B and SHP but the effect was reversed by FXR suppressor guggulsterone. Molecular docking results indicated that calycosin could be embedded into the binding pocket of FXR, thereby increasing the expressions of STAT3 tyrosine phosphorylation and its target genes, Bcl-xl and SOCS3. Conclusions Calycosin plays a critical role in hepatoprotection against liver injury in association with FXR activation and STAT3 phosphorylation.