Biomolecules & Therapeutics

  • 제21권4호
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  • Pages.264-269
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  • 2013
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Silymarin's Protective Effects and Possible Mechanisms on Alcoholic Fatty Liver for Rats

  • Zhang, Wei (Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Key Laboratory of Digestive Disease of Anhui Province) ;
  • Hong, Rutao (Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Key Laboratory of Digestive Disease of Anhui Province) ;
  • Tian, Tulei (Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Key Laboratory of Digestive Disease of Anhui Province)
  • 투고 : 2013.03.05
  • 심사 : 2013.07.05
  • 발행 : 2013.07.31
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초록

Silymarin has been introduced fairly recently as a hepatoprotective agent. But its mechanisms of action still have not been well established. The aim of this study was to make alcoholic fatty liver model of rats in a short time and investigate silymarin's protective effects and possible mechanisms on alcoholic fatty liver for rats. The model of rat's alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. Histopathological changes were assessed by hematoxylin and eosin staining (HE). The activities of alanine transarninase (ALT) and aspartate aminotransferase (AST), the levels of total bilirubin (TBIL), total cholesterol (TC) and triglyceride (TG) in serum were detected with routine laboratory methods using an autoanalyzer. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in liver homogenates were measured by spectrophotometry. The TG content in liver tissue was determined by spectrophotometry. The expression of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in the liver were analyzed by immunohistochemistry. Silymarin effectively protected liver from alcohol-induced injury as evidenced by improving histological damage situation, reducing ALT and AST activities and TBIL level in serum, increasing SOD and GPx activities and decreasing MDA content in liver homogenates and reducing TG content in liver tissue. Additionally, silymarin markedly downregulated the expression of NF-${\kappa}B$ p65, ICAM-1 and IL-6 in liver tissue. In conclusion, Silymarin could protect against the liver injury caused by ethanol administration. The effect may be related to alleviating lipid peroxidation and inhibiting the expression of NF-${\kappa}B$.

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참고문헌

  1. Arteel, G. E. (2003) Oxidants and antioxidants in alcohol-induced liver disease. Gastroenterology 124, 778-790. https://doi.org/10.1053/gast.2003.50087
  2. Ajamieh, H. H., Menendez, S., Martenez-Sanchez, G., Candelario-Jalil, E., Re, L., Giuliani, A. and Fernandez, O. S. (2004) Effects of ozone oxidative preconditioning on nitric oxide generation and cellular redox balance in a rat model of hepatic ischaemia-reperfusion. Liver Int. 24, 55-62. https://doi.org/10.1111/j.1478-3231.2004.00885.x
  3. Barnes, P. J. and Karin, M. (1997) Nuclear factor $\kappa{B}$-a pivotal factor in chronic infl ammatory diseases. N. Engl. J. Med. 336, 1066-1071. https://doi.org/10.1056/NEJM199704103361506
  4. Banerjee, A., Rose, R., Johnson, G. A., Burghardt, R. C. and Ramaiah, S. K. (2009) The infl uence of estrogen on hepatobiliary osteopontin (SPP1) expression in a female rodent model of alcoholic steatohepatitis. Toxicol. Pathol. 37, 492-501. https://doi.org/10.1177/0192623309335633
  5. Chen, F., Castranova, V., Shi, X. and Demers, L. M. (1999) New insights into the role of nuclear factor-$\kappa{B}$, a ubiquitous transcription factor in the initiation of diseases. Clin. Chem. 45, 7-17.
  6. Chen, S. L., Hong, R. T., Diao, L., Ruan, H. L., Xu, J. and Mei, Q. (2010) Silymarin protects against acute ethanol-induced liver injury in rats. Acta Universitatis Medicinalis Anhui. 45, 209-212.
  7. Eagon, P. K. (2010) Alcoholic liver injury: Infl uence of gender and hormones. World J. Gastroenterol. 16,1377-1384. https://doi.org/10.3748/wjg.v16.i11.1377
  8. Fraschini, F., Demartini, G. and Esposti, D. (2002) Pharmacology of silymarin. Clin. Drug Invest. 22, 51-65. https://doi.org/10.2165/00044011-200222010-00007
  9. Kiruthiga, P. V., Shafreen, R. B., Pandian, S. K. and Devi, K. P. (2007) Silymarin protection against major reactive oxygen species released by environmental toxins: exogenous $H_{2}O_{2}$ exposure in erythrocytes. Basic Clin. Pharmacol. Toxicol. 100, 414-419. https://doi.org/10.1111/j.1742-7843.2007.00069.x
  10. Luper, S. (1998) A review of plants used in the treatment of liver disease: part 1. Altern. Med. Rev. 3, 410-421.
  11. Nanji, A. A. (2004) Role of different dietary fatty acids in the pathogenesis of experimental alcoholic liver disease. Alcohol 34, 21-25. https://doi.org/10.1016/j.alcohol.2004.08.005
  12. Nanji, A. A., Jokelainen, K., Rahemtulla, A., Miao, L., Fogt, F., Matsumoto, H., Tahan, S. R. and Su, G. L. (1999) Activation of nuclear factor $\kappa{B}$ and cytokine imbalance in experimental alcoholic liver disease in the rat. Hepatology 30, 934-943. https://doi.org/10.1002/hep.510300402
  13. Nanji, A. A., Jokelainen, K., Tipoe, G. L., Rahemtulla, A., Thomas, P. and Dannenberg, A. J. (2003) Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-$\kappa{B}$dependent genes. Am. J. Physiol. Gastrointest. Liver Physiol. 284, G321-327. https://doi.org/10.1152/ajpgi.00230.2002
  14. Neurath, M. F., Pettersson, S., Meyer zum Buschenfelde, K. H. and Strober W. (1996) Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-$\kappa{B}$ abrogates established experimental colitis in mice. Nat. Med. 2, 998-1004. https://doi.org/10.1038/nm0996-998
  15. Polyak, S. J., Morishima, C., Lohmann, V., Pal, S., Lee, D. Y., Liu, Y., Graf, T. N. and Oberlies, N. H. (2010) Identifi cation of hepatoprotective fl avonolignans from silymarin. Proc. Natl. Acad Sci. U.S.A. 107, 5995-5999. https://doi.org/10.1073/pnas.0914009107
  16. Purohit, V., Russo, D. and Coates, P. M. (2004) Role of fatty liver, dietary fatty acid supplements, and obesity in the progression of alcoholic liver disease: introduction and summary of the symposium. Alcohol 34, 3-8. https://doi.org/10.1016/j.alcohol.2004.06.008
  17. Polavarapu, R., Spitz, D. R., Sim, J. E., Follansbee, M. H., Oberley, L. W., Rahemtulla, A. and Nanji, A. A. (1998) Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fi sh oil. Hepatology 27,1317-1323. https://doi.org/10.1002/hep.510270518
  18. Song, Z., Deaciuc, I., Song, M., Lee, D. Y., Liu, Y., Ji, X. and McClain, C. (2006) Silymarin protects against acute ethanol-induced hepatotoxicity in mice. Alcohol Clin. Exp. Res. 30, 407-413. https://doi.org/10.1111/j.1530-0277.2006.00063.x
  19. Saller, R., Meier, R. and Brignoli, R. (2001) The use of silymarin in the treatment of liver diseases. Drugs 61, 2035-2063. https://doi.org/10.2165/00003495-200161140-00003
  20. Shi, Q. Z., Wang, L. W., Zhang, W. and Gong, Z. J. (2010) Betaine inhibits Toll-like receptor 4 expression in rats with ethanol-induced liver injury. World J. Gastroenterol. 16, 897-903.
  21. Tilg, H. and Diehl, A. M. (2000) Cytokines in alcoholic and nonalcoholic steatohepatitis. N. Engl. J. Med. 343,1467-1476. https://doi.org/10.1056/NEJM200011163432007
  22. Zhou, J., Zhai, Y., Mu, Y., Gong, H., Uppal, H., Toma, D., Ren, S., Evans, R. M. and Xie, W. (2006) A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J. Biol. Chem. 281, 15013-15020. https://doi.org/10.1074/jbc.M511116200

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  1. Dietary umbelliferone attenuates alcohol-induced fatty liver via regulation of PPARα and SREBP-1c in rats vol.48, pp.7, 2014, https://doi.org/10.1016/j.alcohol.2014.08.008
  2. Down-Regulation of NFkB, Bax,TGF-β, Smad-2mRNA expression in the Livers of Carbon Tetrachloride Treated Rats using Different Natural Antioxidants vol.59, pp.0, 2016, https://doi.org/10.1590/1678-4324-2016150553
  3. Inhibition of ERK1/2 by silymarin in mouse mesangial cells vol.21, pp.1, 2017, https://doi.org/10.4196/kjpp.2017.21.1.117
  4. Melatonin Upregulates the Activity of AMPK and Attenuates Lipid Accumulation in Alcohol-induced Rats vol.51, pp.1, 2016, https://doi.org/10.1093/alcalc/agv126
  5. Dual effect of silymarin on experimental non-alcoholic steatohepatitis induced by irinotecan vol.327, 2017, https://doi.org/10.1016/j.taap.2017.04.023
  6. Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination? vol.22, pp.1, 2016, https://doi.org/10.3748/wjg.v22.i1.8
  7. Beneficial Effects of Silymarin After the Discontinuation of CCl4-Induced Liver Fibrosis vol.19, pp.8, 2016, https://doi.org/10.1089/jmf.2015.0104
  8. The impact of silymarin on antioxidant and oxidative status in patients with β-thalassemia major: A crossover, randomized controlled trial vol.35, 2017, https://doi.org/10.1016/j.ctim.2017.08.007
  9. Protective effects of combined β-caryophyllene and silymarin against ketoprofen-induced hepatotoxicity in rats vol.94, pp.7, 2016, https://doi.org/10.1139/cjpp-2015-0607
  10. Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo vol.21, pp.12, 2016, https://doi.org/10.3390/molecules21111456
  11. Coordinated regulation of scopoletin at adipose tissue–liver axis improved alcohol-induced lipid dysmetabolism and inflammation in rats vol.237, pp.3, 2015, https://doi.org/10.1016/j.toxlet.2015.06.016
  12. Silymarin Inhibits Morphological Changes in LPS-Stimulated Macrophages by Blocking NF-κB Pathway vol.19, pp.3, 2015, https://doi.org/10.4196/kjpp.2015.19.3.211
  13. Plasma metabonomic analysis reveals the effects of salvianic acid on alleviating acute alcoholic liver damage vol.5, pp.46, 2015, https://doi.org/10.1039/C5RA00823A
  14. Multicolor Fluorescence Detection-Based Microfluidic Device for Single-Cell Metabolomics: Simultaneous Quantitation of Multiple Small Molecules in Primary Liver Cells vol.88, pp.17, 2016, https://doi.org/10.1021/acs.analchem.6b01775
  15. Apigenin protects against alcohol-induced liver injury in mice by regulating hepatic CYP2E1-mediated oxidative stress and PPARα-mediated lipogenic gene expression vol.275, 2017, https://doi.org/10.1016/j.cbi.2017.08.006
  16. Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway vol.22, pp.4, 2014, https://doi.org/10.4062/biomolther.2014.072
  17. A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives vol.90, pp.1, 2016, https://doi.org/10.1007/s00204-015-1580-z
  18. Iron-chelating effect of silymarin in patients with β-thalassemia major: A crossover randomised control trial vol.32, pp.3, 2017, https://doi.org/10.1002/ptr.5995
  19. Plant-derived antivirals against hepatitis c virus infection vol.15, pp.1, 2018, https://doi.org/10.1186/s12985-018-0945-3
  20. -Galactosamine-Induced Acute Liver Injury in Rats vol.21, pp.10, 2018, https://doi.org/10.1089/jmf.2018.4178
  21. Silybin Alleviates Hepatic Steatosis and Fibrosis in NASH Mice by Inhibiting Oxidative Stress and Involvement with the Nf-κB Pathway pp.1573-2568, 2018, https://doi.org/10.1007/s10620-018-5268-0
  22. Enhancement of Silymarin Anti-fibrotic Effects by Complexation With Hydroxypropyl (HPBCD) and Randomly Methylated (RAMEB) β-Cyclodextrins in a Mouse Model of Liver Fibrosis vol.9, pp.1663-9812, 2018, https://doi.org/10.3389/fphar.2018.00883
  23. Resveratrol Ameliorates Experimental Alcoholic Liver Disease by Modulating Oxidative Stress vol.2017, pp.None, 2013, https://doi.org/10.1155/2017/4287890
  24. Protective effects of silymarin on triptolide-induced acute hepatotoxicity in rats vol.17, pp.1, 2013, https://doi.org/10.3892/mmr.2017.7958
  25. Apigenin inhibits ethanol-induced oxidative stress and LPS-induced inflammatory cytokine production in cultured rat hepatocytes vol.16, pp.1, 2013, https://doi.org/10.1016/j.jab.2017.11.006
  26. A therapeutic insight of carbohydrate and fixed oil from Plantago ovata L. seeds against ketoprofen-induced hepatorenal toxicity in rats vol.42, pp.1, 2013, https://doi.org/10.1186/s42269-018-0031-4
  27. Magnolol Prevents Acute Alcoholic Liver Damage by Activating PI3K/Nrf2/PPARγ and Inhibiting NLRP3 Signaling Pathway vol.10, pp.None, 2019, https://doi.org/10.3389/fphar.2019.01459
  28. Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats vol.55, pp.5, 2013, https://doi.org/10.3390/medicina55050181
  29. Nonalcoholic Fatty Liver Disease: Pathogenesis and Treatment in Traditional Chinese Medicine and Western Medicine vol.2020, pp.None, 2013, https://doi.org/10.1155/2020/8749564
  30. Modulation of the TLR4/MyD88/NF- κ B Pathway by Humulus japonicus Extract Protects Against Alcohol-Induced Liver Injury in a Rat Model vol.24, pp.1, 2013, https://doi.org/10.1089/jmf.2019.4650
  31. Effect of Silymarin and Quercetin in a Miniaturized Scaffold in Wistar Rats against Non-alcoholic Fatty Liver Disease vol.6, pp.32, 2013, https://doi.org/10.1021/acsomega.1c00555