DOI QR코드

DOI QR Code

Protective effect of ultrasonication-processed ginseng berry extract on the D-galactosamine/lipopolysaccharide-induced liver injury model in rats

  • Nam, Yoonjin (Department of Pharmacology, College of Pharmacy, Chung-Ang University) ;
  • Bae, Jinhyung (Department of Pharmacology, College of Pharmacy, Chung-Ang University) ;
  • Jeong, Ji Hoon (Department of Pharmacology, College of Medicine, Chung-Ang University) ;
  • Ko, Sung Kwon (Department of Oriental Medical Food & Nutrition, Semyung University) ;
  • Sohn, Uy Dong (Department of Pharmacology, College of Pharmacy, Chung-Ang University)
  • 투고 : 2017.05.30
  • 심사 : 2017.07.20
  • 발행 : 2018.10.15

초록

Background: Acute hepatic failure is a life-threatening critical condition associated with rapid deterioration of liver function and liver transplantation. Several studies have shown that Panax ginseng Mayer has antidiabetic and hepatoprotective effects. However, the hepatoprotective effect of ginseng berry is still unveiled. In this study, we evaluated the hepatoprotective effects of ultrasonication-processed ginseng berry extract (UGBE) on acute hepatic failure model in rats. Methods: Ginseng berry extract (GBE) was ultrasonically processed. The GBE, silymarin, and UGBE were orally administered to male Sprague-Dawley rats for 4 wk. Twenty-four h after the last administration, rats were challenged with D-galactosamine (D-GalN)/lipopolysaccharide (LPS). Results: After ultrasonication, the component ratio of ginsenosides Rg2, Rg3, Rh1, Rh4, Rk1, Rk3, and F4 in GBE had been elevated. Administration of UGBE significantly increased the survival rate of D-GalN/LPS-challenged rats. Pretreatment with UGBE significantly decreased serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels in D-GalN/LPS-challenged rats in a dose-dependent manner. The levels of enzymatic markers for oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and glutathione) were increased by UGBE treatment in a dose-dependent manner. Tumor necrosis factor alphalevel, inducible nitric oxide synthase activities, and nitric oxide productions were reduced by UGBE treatment. In addition, hemeoxygenase-1 levels in liver were also significantly increased in the UGBE-treated group. The protein expression of toll-like receptor 4 was decreased by UGBE administration. Hematoxylin and eosin staining results also supported the results of this study showing normal appearance of liver histopathology in the UGBE-treated group. Conclusion: UGBE showed a great hepatoprotective effect on D-GalN/LPS-challenged rats via the toll-like receptor 4 signaling pathway.

키워드

참고문헌

  1. Zhang S, Yang N, Ni S, Li W, Xu L, Dong P, Lu M. Pretreatment of lipopolysaccharide (LPS) ameliorates D-GalN/LPS induced acute liver failure through TLR4 signaling pathway. Int J Clin Exp Pathol 2014;7:6626-34.
  2. Bernal W, Wendon J. Acute liver failure. N Engl J Med 2013;369:2525-34. https://doi.org/10.1056/NEJMra1208937
  3. Schiodt FV, Lee WM. Fulminant liver disease. Clin Liver Dis 2003;7:331-49. vi. https://doi.org/10.1016/S1089-3261(03)00026-6
  4. Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Lancet 2010;376:190-201. https://doi.org/10.1016/S0140-6736(10)60274-7
  5. Wang Y, Li Y, Xie J, Zhang Y, Wang J, Sun X, Zhang H. Protective effects of probiotic Lactobacillus casei Zhang against endotoxin- and D-galactosamineinduced liver injury in rats via anti-oxidative and anti-inflammatory capacities. Int Immunopharmacol 2013;15:30-7. https://doi.org/10.1016/j.intimp.2012.10.026
  6. Zhou R, Li Z, He C, Li R, Xia H, Li C, Xiao J, Chen ZY. Human umbilical cord mesenchymal stem cells and derived hepatocyte-like cells exhibit similar therapeutic effects on an acute liver failure mouse model. PloS One 2014;9:e104392. https://doi.org/10.1371/journal.pone.0104392
  7. Decker K, Keppler D. Galactosamine hepatitis: key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev Physiol Biochem Pharmacol 1974;71:77-106.
  8. Galanos C, Freudenberg MA, Reutter W. Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci U S A 1979;76:5939-43. https://doi.org/10.1073/pnas.76.11.5939
  9. Rietschel ET, Brade H. Bacterial endotoxins. Sci Am 1992;267:54-61.
  10. Nowak M, Gaines GC, Rosenberg J, Minter R, Bahjat FR, Rectenwald J, MacKay SL, Edwards 3rd CK, Moldawer LL. LPS-induced liver injury in Dgalactosamine-sensitized mice requires secreted TNF-alpha and the TNF-p55 receptor. Am J Physiol Regul Integr Comp Physiol 2000;278:R1202-9. https://doi.org/10.1152/ajpregu.2000.278.5.R1202
  11. Su GL. Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation. Am J Physiol Gastrointest Liver Physiol 2002;283:G256-65. https://doi.org/10.1152/ajpgi.00550.2001
  12. El-Agamy DS, Makled MN, Gamil NM. Protective effects of agmatine against Dgalactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice. Inflammopharmacology 2014;22:187-94. https://doi.org/10.1007/s10787-013-0188-2
  13. Inoue T, Horiai H, Aoki C, Kawamura I, Ota M, Mizuhara H, Tomoi M, Mutoh S. Insulin-like growth factor-I prevents lethal acute liver failure induced by dgalactosamine and lipopolysaccharide in rats. Vivo 2003;17:293-9.
  14. Yun TK. Panax ginsengda non-organ-specific cancer preventive? Lancet Oncol 2001;2:49-55. https://doi.org/10.1016/S1470-2045(00)00196-0
  15. Yang SO, Park HR, Sohn ES, Lee SW, Kim HD, Kim YC, Kim KH, Na SW, Choi HK, Arasu MV, et al. Classification of ginseng berry (Panax ginseng C.A. Meyer) extract using 1h NMR spectroscopy and its inhibition of lipid accumulation in 3 T3-L1 cells. BMC Complement Altern Med 2014;14:455. https://doi.org/10.1186/1472-6882-14-455
  16. Ma L, Liu H, Xie Z, Yang S, Xu W, Hou J, Yu B. Ginsenoside rb3 protects cardiomyocytes against ischemia-reperfusion injury via the inhibition of JNKmediated NF-kappab pathway: a mouse cardiomyocyte model. PloS One 2014;9:e103628. https://doi.org/10.1371/journal.pone.0103628
  17. Kim CK, Cho DH, Lee KS, Lee DK, Park CW, Kim WG, Lee SJ, Ha KS, Goo Taeg O, Kwon YG, et al. Ginseng berry extract prevents atherogenesis via antiinflammatory action by upregulating phase II gene expression. Evid Based Complement Altern Med 2012;2012:490301.
  18. Jang HJ, Han IH, Kim YJ, Yamabe N, Lee D, Hwang GS, Oh M, Choi KC, Kim SN, Ham J, et al. Anticarcinogenic effects of products of heat-processed ginsenoside re, a major constituent of ginseng berry, on human gastric cancer cells. J Agric Food Chem 2014;62:2830-6. https://doi.org/10.1021/jf5000776
  19. Kim YK, Yoo DS, Xu H, Park NI, Kim HH, Choi JE, Park SU. Ginsenoside content of berries and roots of three typical Korean ginseng (Panax ginseng) cultivars. Nat Prod Commun 2009;4:903-6.
  20. Quan HY, Yuan HD, Jung MS, Ko SK, Park YG, Chung SH. Ginsenoside Re lowers blood glucose and lipid levels via activation of AMP-activated protein kinase in HepG2 cells and high-fat diet fed mice. Int J Mol Med 2012;29:73-80.
  21. Liu Y, Ma H, Zhang JW, Deng MC, Yang L. Influence of ginsenoside Rh1 and F1 on human cytochrome p450 enzymes. Planta Med 2006;72:126-31. https://doi.org/10.1055/s-2005-873197
  22. Sung KC, Ryan MC, Kim BS, Cho YK, Kim BI, Reaven GM. Relationships between estimates of adiposity, insulin resistance, and nonalcoholic fatty liver disease in a large group of nondiabetic Korean adults. Diabetes Care 2007;30:2113-8. https://doi.org/10.2337/dc07-0512
  23. Jung H, Bae J, Ko SK, Sohn UD. Ultrasonication processed Panax ginseng berry extract induces apoptosis through an intrinsic apoptosis pathway in HepG2 cells. Arch Pharm Res 2016;39:855-62. https://doi.org/10.1007/s12272-016-0760-6
  24. Lee SA, Jo HK, Im BO, Kim S, Whang WK, Ko SK. Changes in the contents of prosapogenin in the red ginseng (Panax ginseng) depending on steaming batches. J Ginseng Res 2012;36:102-6. https://doi.org/10.5142/jgr.2012.36.1.102
  25. Paul S, Shin HS, Kang SC. Inhibition of inflammations and macrophage activation by ginsenoside-Re isolated from Korean ginseng (Panax ginseng C.A. Meyer). Food Chem Toxicol 2012;50:1354-61. https://doi.org/10.1016/j.fct.2012.02.035
  26. Kim MH, Lee YC, Choi SY, Cho CW, Rho J, Lee KW. The changes of ginsenoside patterns in red ginseng processed by organic acid impregnation pretreatment. J Ginseng Res 2011;35:497-503. https://doi.org/10.5142/jgr.2011.35.4.497
  27. Park HM, Kim SJ, Kim JS, Kang HS. Reactive oxygen species mediated ginsenoside Rg3- and Rh2-induced apoptosis in hepatoma cells through mitochondrial signaling pathways. Food Chem Toxicol 2012;50:2736-41. https://doi.org/10.1016/j.fct.2012.05.027
  28. Kim YJ, Kwon HC, Ko H, Park JH, Kim HY, Yoo JH, Yang HO. Anti-tumor activity of the ginsenoside rk1 in human hepatocellular carcinoma cells through inhibition of telomerase activity and induction of apoptosis. Biol Pharm Bull 2008;31:826-30. https://doi.org/10.1248/bpb.31.826
  29. Ko H, Kim YJ, Park JS, Park JH, Yang HO. Autophagy inhibition enhances apoptosis induced by ginsenoside Rk1 in hepatocellular carcinoma cells. Biosci Biotechnol Biochem 2009;73:2183-9. https://doi.org/10.1271/bbb.90250
  30. Lee CK, Park KK, Chung AS, Chung WY. Ginsenoside Rg3 enhances the chemosensitivity of tumors to cisplatin by reducing the basal level of nuclear factor erythroid 2-related factor 2-mediated heme oxygenase-1/nad(p)h quinone oxidoreductase-1 and prevents normal tissue damage by scavenging cisplatin-induced intracellular reactive oxygen species. Food Chem Toxicol 2012;50:2565-74. https://doi.org/10.1016/j.fct.2012.01.005
  31. Park EK, Choo MK, Han MJ, Kim DH. Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities. Int Arch Allergy Immunol 2004;133:113-20. https://doi.org/10.1159/000076383
  32. Chen B, Shen YP, Zhang DF, Cheng J, Jia XB. The apoptosis-inducing effect of ginsenoside F4 from steamed notoginseng on human lymphocytoma JK cells. Nat Prod Res 2013;27:2351-4. https://doi.org/10.1080/14786419.2013.828290
  33. Maezona K, Mawatari K, Kajiwara K, Shinkai A, Maki T. Effect of alanine on Dgalactosamine induced acute liver failure in rats. J Hepatol 1996;24:1211-6.
  34. Lu J, Chen YP, Wan R, Guo CY, Wang XP. Protective effects of ulinastatin on acute liver failure induced by lipopolysaccharide/D-galactosamine. Digest Dis Sci 2012;57:399-404. https://doi.org/10.1007/s10620-011-1927-0
  35. Singal AK, Jampana SC, Weinman SA. Antioxidants as therapeutic agents for liver disease. Liver Int 2011;31:1432-48. https://doi.org/10.1111/j.1478-3231.2011.02604.x
  36. Esrefoglu M. Oxidative stress and benefits of antioxidant agents in acute and chronic hepatitis. Hepat Mon 2012;12:160-7. https://doi.org/10.5812/hepatmon.5090
  37. Ai G, Liu Q, Hua W, Huang Z, Wang D. Hepatoprotective evaluation of the total flavonoids extracted from flowers of Abelmoschus manihot (L.) Medic: in vitro and in vivo studies. J Ethnopharmacol 2013;146:794-802. https://doi.org/10.1016/j.jep.2013.02.005
  38. Xia X, Su C, Fu J, Zhang P, Jiang X, Xu D, Hu L, Song E, Song Y. Role of alphalipoic acid in LPS/D-GalN induced fulminant hepatic failure in mice: studies on oxidative stress, inflammation and apoptosis. Int Immunopharmacol 2014;22:293-302. https://doi.org/10.1016/j.intimp.2014.07.008
  39. Bray RC, Cockle SA, Fielden EM, Roberts PB, Rotilio G, Calabrese L. Reduction and inactivation of superoxide dismutase by hydrogen peroxide. Biochem J 1974;139:43-8. https://doi.org/10.1042/bj1390043
  40. Kono Y, Fridovich I. Superoxide radical inhibits catalase. J Biol Chem 1982;257:5751-4.
  41. Tabatabaie T, Floyd RA. Susceptibility of glutathione peroxidase and glutathione reductase to oxidative damage and the protective effect of spin trapping agents. Arch Biochem Biophys 1994;314:112-9. https://doi.org/10.1006/abbi.1994.1418
  42. Neihorster M, Inoue M, Wendel A. A link between extracellular reactive oxygen and endotoxin-induced release of tumour necrosis factor alpha in vivo. Biochem Pharmacol 1992;43:1151-4.
  43. Liu TZ, Lee KT, Chern CL, Cheng JT, Stern A, Tsai LY. Free radical-triggered hepatic injury of experimental obstructive jaundice of rats involves overproduction of proinflammatory cytokines and enhanced activation of nuclear factor kappab. Ann Clin Lab Sci 2001;31:383-90.
  44. El-Beshbishy HA. Aqueous garlic extract attenuates hepatitis and oxidative stress induced by galactosamine/lipopolysaccharide in rats. Phytother Res 2008;22:1372-9. https://doi.org/10.1002/ptr.2505
  45. Roller J, Laschke MW, Scheuer C, Menger MD. Heme oxygenase (HO)-1 protects from lipopolysaccharide (LPS)-mediated liver injury by inhibition of hepatic leukocyte accumulation and improvement of microvascular perfusion. Langenbeck Arch Surgery 2010;395:387-94. https://doi.org/10.1007/s00423-010-0603-8
  46. Gomes AS, Gadelha GG, Lima SJ, Garcia JA, Medeiros JV, Havt A, Lima AA, Ribeiro RA, Brito GA, Cunha FQ, et al. Gastroprotective effect of hemeoxygenase 1/biliverdin/CO pathway in ethanol-induced gastric damage in mice. Eur J Pharmacol 2010;642:140-5. https://doi.org/10.1016/j.ejphar.2010.05.023
  47. Lekic N, Canova NK, Horinek A, Farghali H. The involvement of heme oxygenase 1 but not nitric oxide synthase 2 in a hepatoprotective action of quercetin in lipopolysaccharide-induced hepatotoxicity of D-galactosamine sensitized rats. Fitoterapia 2013;87:20-6. https://doi.org/10.1016/j.fitote.2013.03.016
  48. Stadler K, Bonini MG, Dallas S, Jiang J, Radi R, Mason RP, Kadiiska MB. Involvement of inducible nitric oxide synthase in hydroxyl radical-mediated lipid peroxidation in streptozotocin-induced diabetes. Free Radic Biol Med 2008;45:866-74. https://doi.org/10.1016/j.freeradbiomed.2008.06.023
  49. Loguercio C, Federico A. Oxidative stress in viral and alcoholic hepatitis. Free Radic Biol Med 2003;34:1-10. https://doi.org/10.1016/S0891-5849(02)01167-X
  50. Mandrekar P, Szabo G. Signalling pathways in alcohol-induced liver inflammation. J Hepatol 2009;50:1258-66. https://doi.org/10.1016/j.jhep.2009.03.007
  51. Inokuchi S, Tsukamoto H, Park E, Liu ZX, Brenner DA, Seki E. Toll-like receptor 4 mediates alcohol-induced steatohepatitis through bone marrowderived and endogenous liver cells in mice. Alcohol Clin Exp Res 2011;35:1509-18.
  52. Szabo G, Bala S. Alcoholic liver disease and the gut-liver axis. World J Gastroenterol 2010;16:1321-9. https://doi.org/10.3748/wjg.v16.i11.1321

피인용 문헌

  1. Protective Effects of Sesquiterpenoids from the Root of Panax ginseng on Fulminant Liver Injury Induced by Lipopolysaccharide/D-Galactosamine vol.66, pp.29, 2018, https://doi.org/10.1021/acs.jafc.8b02627
  2. Hepatoprotective effect of sodium hydrosulfide on hepatic encephalopathy in rats vol.23, pp.4, 2019, https://doi.org/10.4196/kjpp.2019.23.4.263
  3. Effects of Harvest Time on Phytochemical Constituents and Biological Activities of Panax ginseng Berry Extracts vol.24, pp.18, 2018, https://doi.org/10.3390/molecules24183343
  4. Protective effect of hypoglycemic granule against diabetes‐induced liver injury by alleviating glycolipid metabolic disorder and oxidative stress vol.121, pp.5, 2018, https://doi.org/10.1002/jcb.29588
  5. Recent nano-, micro- and macrotechnological applications of ultrasonication in food-based systems vol.61, pp.4, 2018, https://doi.org/10.1080/10408398.2020.1740646