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Protective Effect of Myeongganbo Extract on Acetaminophen-Induced Liver Injury

명간보(明肝補) 추출물의 Acetaminophen 유도 간 손상에 대한 보호효과

  • Kim, Hong-Jun (Department of Oriental Medical Prescription, Woosuk University) ;
  • Mok, Ji-Ye (School of Alternative Medicine & Health Science, College of Alternative Medicine, Jeonju University) ;
  • Park, Kwang-Hyun (Department of Biochemistry, Chonbuk National University Medical School) ;
  • Jeon, In-Hwa (School of Alternative Medicine & Health Science, College of Alternative Medicine, Jeonju University) ;
  • Kim, Hyeon-Soo (School of Alternative Medicine & Health Science, College of Alternative Medicine, Jeonju University) ;
  • Hwang, Sung-Yeoun (Department of Oriental Medical Prescription, Woosuk University) ;
  • Jang, Seon-Il (School of Alternative Medicine & Health Science, College of Alternative Medicine, Jeonju University)
  • 김홍준 (우석대학교 한의과대학 방제학교실) ;
  • 목지예 (전주대학교 대체의학대학 대체건강관리학부) ;
  • 박광현 (전북대학교 의학전문대학 생화학교실) ;
  • 전인화 (전주대학교 대체의학대학 대체건강관리학부) ;
  • 김현수 (전주대학교 대체의학대학 대체건강관리학부) ;
  • 황성연 (우석대학교 한의과대학 방제학교실) ;
  • 장선일 (전주대학교 대체의학대학 대체건강관리학부)
  • Received : 2012.02.07
  • Accepted : 2012.03.16
  • Published : 2012.03.30

Abstract

Objective : Myeongganbo (MGB) composited with Hovenia Semen, Puerariae Radix and Dioscoreae Rhizoma is the prescription for protection of liver function. The purpose of this study was to investigate the effects of MGB extract against acetaminophen (APAP)-induced liver injury in mice. Methods : MGB extract was prepared by extracting with hot distilled water. The extract was freeze-dried following filtration through vacuum distillation system. Mice fasted for overnight were orally administrated with or without MGB extract of different doses (25-200 mg/kg/day). After 30 min, APAP was orally applied with a single dose (400 mg/kg). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in plasmas of mice. Glutathione (GSH), glutathione peroxidase GSH-px), cyclooxygenase-2 (COX-2) activity and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level were investigated in liver homogenates. Liver sections were stained with haematoxylin & eosin, anti-TNF-${\alpha}$ and anti-mouse COX-2 antibodies. Results : APAP treatment remarkably increased AST and ALT activities in plasma but inhibited GSH and GSH-px levels in liver homogenates. Also, liver injury was significantly accelerated by APAP treatment. Furthermore, APAP remarkably elevated COX-2 activity and TNF-${\alpha}$ levels in liver homogenates. However, administration of MGB extract was able to counteract these effects. Histological studies provided supportive evidence for biochemical and molecular analysis Conclusions : These results suggest that MGB extract has potent hepatoprotective effect against APAP-induced liver injury, these properties may contribute to liver disease care.

Keywords

References

  1. Herbology Editorial Committee of Korean Medicine schools. Herbology[Boncho-hak]. Seoul:Young-Lim Press. 2007:184, 580, 734.
  2. Dae-Hwan Youn, Jong-Gil Jeong, Chang-Su Na. Effects of Propolis oral administration according to mixture with Hovenia dulcis Thunb. and Artemisia capillaris Thunb. on D-galactosamine-induced liver injury in rats. The Korea journal of herbology. 2006;21:7-19.
  3. Jong Ho Kim, Young Min Seo, Ju Hyun Kim,, Sun Hee Hyun, Sang Lee, Chun Hwa Kim, Mi Jeong Kang, Tae Won Jeon, Soo Hong Yoon, Tae Cheon Jeong. Protective Effects of the Water Extracts of Hovenia dulcis Thunb Against Ethanol-Induced Toxicity in Primary Cultured Rat Hepatocytes. Yakhak Hoeji. 2008;52:56-61.
  4. Jeong-Min Yang, Yung-Joon Jun, Ju-Young Nam, Mi-Young Son, Jung-Suk Sung, Dong-Il Kim. The Cell Protective Effects of Dioscoreae Rhizoma by Antioxidant Activities on HeLa Cells. The Journal of oriental obstetrics & gynecology. 2008;21: 97-107.
  5. Ga-young Choi, Byoung-woo Kim. Experimental Study on the Antioxidant and Antimicrobial Properties of Dioscoreae Rhizoma. Journal of korean oriental internal medicine. 2010;31: 290-7.
  6. Kyung-Hye Jeon, Yoon-Bum Kook. Literature on Applications of Prescriptions Including Pueraria Thunbergiana Bentham in Dongueibogam. The Korean journal of oriental medical prescription. 2009;17:29-43.
  7. Dong Hwan Hyun, Sun Yeong Jung, Sang Shin Jung, Ki Tae Ha, Cheol Ho Kim, Dong Wook Kim, June Ki Kim, Dall Yeong Choi. The Study of Protective Effect of Puerariae Radix against $CCl_{4}$ -induced Hepatotoxicity. Korean journal of oriental physiology & pathology. 2003;17:297-307.
  8. Heyong-Gyoo Park, Jang-Hoon Lee, Hong-Jung Woo. The Effects of Some Oriental Herbs Which Have Been Used in the Treatment of Alcoholic Diseases on Alcoholic Metabolism and Alcoholic Liver Damages. Journal of Korean oriental medical society. 2000;21:186-98.
  9. Ray SD, Mumaw VR, Raje RR, Fariss MW. Protection of acetaminophen-induced hepatocellular apoptosis and necrosis by cholesteryl hemisuccinole pretreatment. J Pharmacol Exp Ther. 1996;279: 1470-83.
  10. Webster PA, Roberts DW, Benson RW, Kearns GL. Acetaminophen toxicity in children:diagnostic confirmation using a specific antigenic biomarker. J Clin Pharmacol. 1996;36:397-402. https://doi.org/10.1002/j.1552-4604.1996.tb05025.x
  11. Albano E, Rundgren M, Harvison PJ, Nelson SD, Moldeus P. Mechanisms of N-acetyl-pbenzoquinone- imine cytotoxicity. Mol Pharmacology. 1985;28:306-11.
  12. Kyle ME, Miccadei S, Nakae D, Farber JL. Superoxide dismutase and catalase protect cultured hepatocytes from the cytotoxicity of acetaminophen. Biochem Biophys Res Commun. 1987;149:889-94. https://doi.org/10.1016/0006-291X(87)90491-8
  13. Mahadevan SB, McKiernan PJ, Davies P, Kelly DA. Paracetamol induced hepatotoxicity. Arch Dis Child. 2006:91:598-603. https://doi.org/10.1136/adc.2005.076836
  14. Ishida Y, Kondo T, Tsuneyama K, Lu P, Takayasu T, Mukaida N. The pathogenic roles of tumor necrosis factor receptor p55 in acetaminopheninduced liver injury in mice. J Leukoc Biol. 2004;75:59-67. https://doi.org/10.1189/jlb.0403152
  15. Hogaboam CM, Bone-Larson CL, Steinhauser ML, Matsukawa A, Gosling J, Boring L, Charo IF, Simpson KJ, Lukacs NW, Kunkel SL. Exaggerated hepatic injury due to acetaminophen challenge in mice lacking C-C chemokine receptor 2.. Am J Pathol. 2000; 156:1245-52. https://doi.org/10.1016/S0002-9440(10)64995-4
  16. Bhave VS, Donthamsetty S, Latendresse JR, Cunningham ML, Mehendale HM. Secretory phospholipase $A_{2}$-mediated progression of hepatotoxicity initiated by acetaminophen is exacerbated in the absence of hepatic COX-2. Toxicol Appl Pharmacol. 2011;251:173-80. https://doi.org/10.1016/j.taap.2011.01.013
  17. Prescott LF. Paracetamol, alcohol and the liver. Br J Clin Pharmacol. 2000;49:291-301. https://doi.org/10.1046/j.1365-2125.2000.00167.x
  18. Burnett BP, Bitto A, Altavilla D, Squadrito F, Levy RM, Pillai L. Flavocoxid inhibits phospholipase A2, peroxidase moieties of the cyclooxygenases (COX), and 5-lipoxygenase, modifies COX-2 gene expression, and acts as an antioxidant. Mediators Inflamm. 2011;2011: 385780.
  19. Du J, He D, Sun LN, Han T, Zhang H, Qin LP, Rahman K. Semen Hoveniae extract protects against acute alcohol-induced liver injury in mice. Pharm Biol. 2010 ; 48:953-958. https://doi.org/10.3109/13880200903300196
  20. Fang HL, Lin HY, Chan MC, Lin WL, Lin WC. Treatment of chronic liver injuries in mice by oral administration of ethanolic extract of the fruit of Hovenia dulcis. Am J Chin Med. 2007;35: 693-703. https://doi.org/10.1142/S0192415X07005181
  21. Hinson JA, Pohl LR, Monks TJ, Gillele JR, Guengerich FP. 3-Hydroxyacetaminophen. A microsomal metabolites of acetaminophen. Evidence against an epoxide as the reactive metabolite of acetaminophen. Drug Metab Dispos. 1980;8:289-94.
  22. Rajesh B, Parames CS. The protein fraction of Phyllanthus niruri plays a protective role against acetaminophen induced hepatic disorder via its antioxidant properties. Phytother Res. 2006;l20: 595-601. https://doi.org/10.1002/ptr.1933
  23. Adamson GM, Harman AW. A role for the glutathione peroxidase/reductase enzyme system in the protection from paracetamol toxicity in isolated mouse hepatocytes. Biochem Pharmacol 1989;38:3323-30. https://doi.org/10.1016/0006-2952(89)90630-8
  24. Ding LS, Liang QL, Teng YF. Study on flavonoids in seeds of Hovenia dulcis . Yao Xue Xue Bao. 1997;32:600-602.
  25. Hase K, Ohsugi M, Xiong Q, Basnet P, Kadota S, Namba T. Hepatoprotective effect of Hovenia dulcis THUNB. on experimental liver injuries induced by carbon tetrachloride or Dgalactosamine/ lipopolysaccharide. Biol Pharm Bull. 1997;20:381-385. https://doi.org/10.1248/bpb.20.381
  26. Jin M, Lu Y, Yang JH, Jo TH, Park YI, Lee CK, Park SJ, Son KH, Chang HW. Anti-inflammatory activity of 6-hydroxy-2,7-dimethoxy-1,4- henanthraquinone from tuberous roots of yam (Dioscorea batatas ) through inhibition of prostaglandin $D_{2}$ and leukotriene $D_{4}$ production in mouse bone marrow-derived mast cells. Arch Pharm Res. 2011;34:1495-1501. https://doi.org/10.1007/s12272-011-0911-8
  27. Xiong Y, Yang Y, Yang J, Chai H, Li Y, Yang J, Jia Z, Wang Z. Tectoridin, an isoflavone glycoside from the flower of Pueraria lobata, prevents acute ethanol-induced liver steatosis in mice. Toxicology. 2010;276:64-72. https://doi.org/10.1016/j.tox.2010.07.007