Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Protective effect of wild ginseng cambial meristematic cells on ᴅ-galactosamine-induced hepatotoxicity in rats

  • Received : 2015.02.26
  • Accepted : 2015.04.13
  • Published : 2015.10.15
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Panax ginseng has a wide range of biological activities including anti-inflammatory, antioxidant, and immunomodulatory functions. Wild ginseng cambial meristematic cells (CMCs) were obtained from P. ginseng cambium. This study examined the protective mechanism of wild ginseng CMCs against $\small{D}$-galactosamine (GalN)-induced liver injury. GalN, a well-known hepatotoxicant, causes severe hepatocellular inflammatory damage and clinical features similar to those of human viral hepatitis in experimental animals. Methods: Hepatotoxicity was induced in rats using GalN (700 mg/kg, i.p.). Wild ginseng CMCs was administered orally once a day for 2 wks, and then 2 h prior to and 6 h after GalN injection. Results: Wild ginseng CMCs attenuated the increase in serum aminotransferase activity that occurs 24 h after GalN injection. Wild ginseng CMCs also attenuated the GalN-induced increase in serum tumor necrosis factor-${\alpha}$, interleukin-6 level, and hepatic cyclooxygenase-2 protein and mRNA expression. Wild ginseng CMCs augmented the increase in serum interleukin -10 and hepatic heme oxygenase-1 protein and mRNA expression that was induced by GalN, inhibited the increase in the nuclear level of nuclear factor-kappa B, and enhanced the increase in NF-E2-related factor 2. Conclusion: Our findings suggest that wild ginseng CMCs protects liver against GalN-induced inflammation by suppressing proinflammatory mediators and enhancing production of anti-inflammatory mediators.

Keywords

References

  1. 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
  2. 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.
  3. Ghosh M, Das J, Sil PC. D(+) galactosamine induced oxidative and nitrosative stress-mediated renal damage in rats via NF-kappaB and inducible nitric oxide synthase (iNOS) pathways is ameliorated by a polyphenol xanthone, mangiferin. Free Radic Res 2012;46:116-32. https://doi.org/10.3109/10715762.2011.644240
  4. Immenschuh S, Baumgart-Vogt E, Mueller S. Heme oxygenase-1 and iron in liver inflammation: a complex alliance. Curr Drug Targets 2010;11:1541-50. https://doi.org/10.2174/1389450111009011541
  5. Shukla R, Kumar M. Role of Panax ginseng as an antioxidant after cadmiuminduced hepatic injuries. Food Chem Toxicol 2009;47:769-73. https://doi.org/10.1016/j.fct.2009.01.002
  6. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93. https://doi.org/10.1016/S0006-2952(99)00212-9
  7. Hofseth LJ, Wargovich MJ. Inflammation, cancer, and targets of ginseng. J Nutr 2007;137:183S-5S. https://doi.org/10.1093/jn/137.1.183S
  8. Yun UW, Yan Z, Amir R, Hong S, Jin YW, Lee EK, Loake GJ. Plant natural products: history, limitations and the potential of cambial meristematic cells. Biotechnol Genet Eng Rev 2012;28:47-59. https://doi.org/10.5661/bger-28-47
  9. Asano S, Otobe K. Production of phytochemicals by using habituated and longterm cultured cells. Plant Biotechnol J 2011;28:51-62. https://doi.org/10.5511/plantbiotechnology.10.1109a
  10. Lee EK, Jin YW, Park JH, Yoo YM, Hong SM, Amir R, Yan Z, Kwon E, Elfick A, Tomlinson S, et al. Cultured cambial meristematic cells as a source of plant natural products. Nat Biotechnol 2010;28:1213-7. https://doi.org/10.1038/nbt.1693
  11. Choi JH, Kang JW, Kim DW, Sung YK, Lee SM. Protective effects of mg-CUD against D-galactosamine-induced hepatotoxicity in rats. Eur J Pharmacol 2011;657:138-43. https://doi.org/10.1016/j.ejphar.2011.01.030
  12. Kang JW, Kim SJ, Kim HY, Cho SH, Kim KN, Lee SG, Lee SM. Protective effects of HV-P411 complex against D-galactosamine-induced hepatotoxicity in rats. Am J Chin Med 2012;40:467-80. https://doi.org/10.1142/S0192415X1250036X
  13. Kang TJ, Moon JS, Lee SY, Yim DS. Polyacetylene compound from Cirsium japonicum var ussuriense inhibits the LPS-induced inflammatory reaction via suppression of NF-${\kappa}$B activity in RAW 264.7 Cells. Biomol ther 2011;19:97-101. https://doi.org/10.4062/biomolther.2011.19.1.097
  14. Yun TK. Brief introduction of Panax ginseng C.A. Meyer. J Korean Med Sci 2001;16:3-5. https://doi.org/10.3346/jkms.2001.16.S.S3
  15. Ahn IO, Lee SS, Lee JH, Lee MJ, Jo BG. Comparison of ginsenoside contents and pattern similarity between root parts of new cultivars in Panax ginseng C.A. Meyer. J Ginseng Res 2008;32:15-8. https://doi.org/10.5142/JGR.2008.32.1.015
  16. Kim YS, Hahn EJ, Murthy HN, Paek KY. Adventitious root growth and ginsenoside accumulation in Panax ginseng cultures as affected by methyl jasmonate. Biotechnol Lett 2004;26:1619-22. https://doi.org/10.1007/s10529-004-3183-2
  17. Stachlewitz RF, Seabra V, Bradford B, Bradham CA, Rusyn I, Germolec D, thurman RG. Glycine and uridine prevent d-galactosamine hepatotoxicity in the rat: role of Kupffer cells. Hepatology 1999;29:737-45. https://doi.org/10.1002/hep.510290335
  18. Komatsu Y, Shiratori Y, Kawase T, Hashimoto N, Han K, Shiina S, Matsumura M, Niwa Y, Kato N, Tada M. Role of polymorphonuclear leukocytes in galactosamine hepatitis: mechanism of adherence to hepatic endothelial cells. Hepatology 1994;20:1548-56. https://doi.org/10.1002/hep.1840200626
  19. Shito M, Balis UJ, Tompkins RG, Yarmush ML, Toner M. A fulminant hepatic failure model in the rat: involvement of interleukin-1beta and tumor necrosis factor-alpha. Dig Dis Sci 2001;46:1700-8. https://doi.org/10.1023/A:1010653504568
  20. Wanner GA, Ertel W, Muller P, Hofer Y, Leiderer R, Menger MD, Messmer K. Liver ischemia and reperfusion induces a systemic inflammatory response through Kupffer cell activation. Shock 1996;5:34-40.
  21. Han C, Li G, Lim K, DeFrances MC, Gandhi CR, Wu T. Transgenic expression of cyclooxygenase-2 in hepatocytes accelerates endotoxin-induced acute liver failure. J Immunol 2008;181:8027-35. https://doi.org/10.4049/jimmunol.181.11.8027
  22. Berzsenyi MD, Roberts SK, Preiss S, Woollard DJ, Beard MR, Skinner NA, Bowden DS, Visvanathan K. Hepatic TLR2 & TLR4 expression correlates with hepatic inflammation and TNF-${\alpha}$ in HCV & HCV/HIV infection. J Viral Hepat 2011;18:852-60. https://doi.org/10.1111/j.1365-2893.2010.01390.x
  23. Soares JB, Pimentel-Nunes P, Afonso L, Rolanda C, Lopes P, Roncon-Albuquerque Jr R, Goncalves N, Boal-Carvalho I, Pardal F, Lopes S, et al. Increased hepatic expression of TLR2 and TLR4 in the hepatic inflammation-fibrosis-carcinoma sequence. Innate Immun 2012;18:700-8. https://doi.org/10.1177/1753425912436762
  24. Mahmoud MF, Hamdan DI, Wink M, El-Shazly AM. Hepatoprotective effect of limonin, a natural limonoid from the seed of Citrus aurantium var. bigaradia, on d-galactosamine-induced liver injury in rats. Naunyn Schmiedebergs Arch Pharmacol 2014;387:251-61. https://doi.org/10.1007/s00210-013-0937-1
  25. Poligone B, Baldwin AS. Positive and negative regulation of NF-kappaB by COX-2: roles of different prostaglandins. J Biol Chem 2001;276:38658-64. https://doi.org/10.1074/jbc.M106599200
  26. Kawai T, Akira S. TLR signaling. Cell Death Differ 2006;13:816-25. https://doi.org/10.1038/sj.cdd.4401850
  27. Kang JW, Kim DW, Choi JS, Kim YS, Lee SM. Scoparone attenuates d-galactosamine/lipopolysaccharide-induced fulminant hepatic failure through inhibition of toll-like receptor 4 signaling in mice. Food Chem Toxicol 2013;57:132-9. https://doi.org/10.1016/j.fct.2013.03.016
  28. Knolle P, Schlaak J, Uhrig A, Kempf P. Meyer zum Buschenfelde KH, Gerken G. Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge. J Hepatol 1995;22:226-9. https://doi.org/10.1016/0168-8278(95)80433-1
  29. Nagaki M, Tanaka M, Sugiyama A, Ohnishi H, Moriwaki H. Interleukin-10 inhibits hepatic injury and tumor necrosis factor-alpha and interferon-gamma mRNA expression induced by staphylococcal enterotoxin B or lipopolysaccharide in galactosamine-sensitized mice. J Hepatol 1999;31:815-24. https://doi.org/10.1016/S0168-8278(99)80282-7
  30. Paine A, Eiz-Vesper B, Blasczyk R, Immenschuh S. Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential. Biochem Pharmacol 2010;80:1895-903. https://doi.org/10.1016/j.bcp.2010.07.014
  31. Sun L, Shi T, Qiao H, Jiang X, Jiang H, Krissansen GW, Sun X. Hepatic overexpression of heme oxygenase-1 improves liver allograft survival by expanding T regulatory cells. J Surg Res 2011;166:187-94. https://doi.org/10.1016/j.jss.2010.11.917
  32. Alam J, Cook JL. Transcriptional regulation of the heme oxygenase-1 gene via the stress response element pathway. Curr Pharm Des 2003;9:2499-511. https://doi.org/10.2174/1381612033453730
  33. Liu J, Wu KC, Lu YF, Ekuase E, Klaassen CD. Nrf2 protection against liver injury produced by various hepatotoxicants. Oxid Med Cell Longev 2013;2013:305861.
  34. Das J, Ghosh J, Roy A, Sil PC. Mangiferin exerts hepatoprotective activity against D-galactosamine induced acute toxicity and oxidative/nitrosative stress via Nrf2-NFkappaB pathways. Toxicol Appl Pharmacol 2012;260:35-47. https://doi.org/10.1016/j.taap.2012.01.015

Cited by

  1. MAPK/AP-1-Targeted Anti-Inflammatory Activities of Xanthium strumarium vol.44, pp.6, 2015, https://doi.org/10.1142/s0192415x16500622
  2. Applicability of Sunsik with Cultivated Wild Ginseng Powder as a Beauty Food vol.16, pp.2, 2015, https://doi.org/10.20402/ajbc.2017.0176
  3. Effectiveness and Safety of Panax ginseng Extract on Hepatic Dysfunction: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial vol.2020, pp.None, 2020, https://doi.org/10.1155/2020/2689565
  4. Renoprotective and therapeutic effects of newly water, ethanol, and butanol ginseng fractions in hypertensive and chronic kidney disease with L-NAME vol.142, pp.None, 2015, https://doi.org/10.1016/j.biopha.2021.111978
  5. Renoprotective and therapeutic effects of newly water, ethanol, and butanol ginseng fractions in hypertensive and chronic kidney disease with L-NAME vol.142, pp.None, 2015, https://doi.org/10.1016/j.biopha.2021.111978