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Acanthopanax koreanum Nakai modulates the immune response by inhibiting TLR 4-dependent cytokine production in rat model of endotoxic shock

  • Jung, Myung-Gi (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Do, Gyeong-Min (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Shin, Jae-Ho (Department of Biomedical Laboratory Science, Eulji University) ;
  • Ham, Young Min (Jeju Biodiversity Research Institute, Jeju Technopark) ;
  • Park, Soo-Yeong (Jeju Biodiversity Research Institute, Jeju Technopark) ;
  • Kwon, Oran (Department of Nutritional Science and Food Management, Ewha Womans University)
  • Received : 2013.05.24
  • Accepted : 2013.07.15
  • Published : 2013.12.01

Abstract

The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced liver failure rats compared with that of acanthoic acid (AA) isolated from AE. Although D-GalN/LPS (250 mg/kg body weight/$10{\mu}g/kg$ body weight, i.p.) induced hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA, equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the result of a significant decrease in the activity of alanine transaminase. Concomitantly, both the nitric oxide and IL-6 levels in the plasma were significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS control (AE0). This response resulted from the regulation of pro-inflammatory signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3 and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and inflammatory cell infiltrates compared to the AE0. In conclusion, these results suggest that especially high-dose AE are capable of alleviating D-GalN/LPS-induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR 4-dependent cytokine release. The anti-inflammatory effect of AE could be contributing to that of AA and AE is better than AA.

Keywords

References

  1. 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.
  2. Mayer AM, Spitzer JA. Modulation of superoxide anion generation by manoalide, arachidonic acid and staurosporine in liver infiltrated neutrophils in a rat model of endotoxemia. J Pharmacol Exp Ther 1993;267:400-9.
  3. Fiuza C, Suffredini AF. Human models of innate immunity: local and systemic inflammatory responses. J Endotoxin Res 2001;7:385-8. https://doi.org/10.1177/09680519010070050701
  4. Ben Ari Z, Avlas O, Pappo O, Zilbermints V, Cheporko Y, Bachmetov L, Zemel R, Shainberg A, Sharon E, Grief F, Hochhauser E. Reduced hepatic injury in Toll-like receptor 4-deficient mice following D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure. Cell Physiol Biochem 2012;29:41-50. https://doi.org/10.1159/000337585
  5. Medvedev AE, Kopydlowski KM, Vogel SN. Inhibition of lipopolysaccharide- induced signal transduction in endotoxin-tolerized mouse macrophages: dysregulation of cytokine, chemokine, and toll-like receptor 2 and 4 gene expression. J Immunol 2000;164: 5564-74. https://doi.org/10.4049/jimmunol.164.11.5564
  6. Kang HS, Kim YH, Lee CS, Lee JJ, Choi I, Pyun KH. Suppression of interleukin-1 and tumor necrosis factor-α production by acanthoic acid, (-)-pimara-9(11),15-dien-19-oic acid, and it antifibrotic effects in vivo. Cell Immunol 1996;170:212-21. https://doi.org/10.1006/cimm.1996.0154
  7. Park EJ, Zhao YZ, Kim YH, Lee JJ, Sohn DH. Acanthoic acid from Acanthopanax koreanum protects against liver injury induced by tert-butyl hydroperoxide or carbon tetrachloride in vitro and in vivo. Planta Med 2004;70:321-7. https://doi.org/10.1055/s-2004-818943
  8. Nan JX, Jin XJ, Lian LH, Cai XF, Jiang YZ, Jin HR, Lee JJ. A diterpenoid acanthoic acid from Acanthopanax koreanum protects against D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice. Biol Pharm Bull 2008;31:738-42. https://doi.org/10.1248/bpb.31.738
  9. Wu YL, Jiang YZ, Jin XJ, Lian LH, Piao JY, Wan Y, Jin HR, Joon Lee J, Nan JX. Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminophen-induced hepatic toxicity in mice. Phytomedicine 2010;17:475-9. https://doi.org/10.1016/j.phymed.2009.07.011
  10. Seki E, De Minicis S, Gwak GY, Kluwe J, Inokuchi S, Bursill CA, Llovet JM, Brenner DA, Schwabe RF. CCR1 and CCR5 promote hepatic fibrosis in mice. J Clin Invest 2009;119:1858-70.
  11. Qureshi ST, Gros P, Malo D. Host resistance to infection: genetic control of lipopolysaccharide responsiveness by TOLL-like receptor genes. Trends Genet 1999;15:291-4. https://doi.org/10.1016/S0168-9525(99)01782-5
  12. Kitazawa T, Tsujimoto T, Kawaratani H, Fujimoto M, Fukui H. Expression of Toll-like receptor 4 in various organs in rats with D-galactosamine-induced acute hepatic failure. J Gastroenterol Hepatol 2008;23:e494-8. https://doi.org/10.1111/j.1440-1746.2007.05246.x
  13. Lee WM. Acute liver failure. N Engl J Med 1993;329:1862-72. https://doi.org/10.1056/NEJM199312163292508
  14. Nakama T, Hirono S, Moriuchi A, Hasuike S, Nagata K, Hori T, Ido A, Hayashi K, Tsubouchi H. Etoposide prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure resulting in reduction of lethality. Hepatology 2001;33:1441-50. https://doi.org/10.1053/jhep.2001.24561
  15. Kawai T, Akira S. TLR signaling. Cell Death Differ 2006;13: 816-25. https://doi.org/10.1038/sj.cdd.4401850
  16. Kawaguchi K, Kikuchi S, Hasegawa H, Maruyama H, Morita H, Kumazawa Y. Suppression of lipopolysaccharide-induced tumor necrosis factor-release and liver injury in mice by naringin. Eur J Pharmacol 1999;368:245-50. https://doi.org/10.1016/S0014-2999(98)00867-X
  17. Wang XL, Mahaney MC, Sim AS, Wang J, Wang J, Blangero J, Almasy L, Badenhop RB, Wilcken DE. Genetic contribution of the endothelial constitutive nitric oxide synthase gene to plasma nitric oxide levels. Arterioscler Thromb Vasc Biol 1997;17: 3147-53. https://doi.org/10.1161/01.ATV.17.11.3147

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