DOI QR코드

DOI QR Code

Evidence of hydrolyzed traditional Korean red ginseng by malted barley on activation of receptor interacting proteins 2 and IkappaB kinase-beta in mouse peritoneal macrophages

  • Rim, Hong-Kun (Department of Pharmacology, College of Oriental Medicine, Institute of Oriental Medicine, Oriental Medical Science Center, Kyung Hee University) ;
  • Kim, Kyu-Yeob (Department of Pharmacology, College of Oriental Medicine, Institute of Oriental Medicine, Oriental Medical Science Center, Kyung Hee University) ;
  • Moon, Phil-Dong (Department of Pharmacology, College of Oriental Medicine, Institute of Oriental Medicine, Oriental Medical Science Center, Kyung Hee University)
  • Received : 2012.05.21
  • Accepted : 2012.08.20
  • Published : 2012.08.31

Abstract

Red ginseng, which has a variety of biological and pharmacological activities including antioxidant, anti-inflammatory, antimutagenic and anticarcinogenic effects, has been used for thousands of years as a general tonic in traditional oriental medicine. Here, we tested the immune regulatory activities of hydrolyzed red ginseng by malted barley (HRG) on the expressions of receptor interacting proteins (Rip) 2 and $I{\kappa}B$ kinase-beta (IKK-${\beta}$) in mouse peritoneal macrophages. We show that HRG increased the activations of Rip 2 and IKK-${\beta}$ for the first time. When HRG was used in combination with recombinant interferon-${\gamma}$ (rIFN-${\gamma}$), there was a marked cooperative induction of nitric oxide (NO) production. The increased expression of inducible NO synthase from rIFN-${\gamma}$ plus HRG-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor-${\kappa}B$ (NF-${\kappa}B$). In addition, the treatment of peritoneal macrophages with rIFN-${\gamma}$ plus HRG caused significant increases in tumor necrosis factor (TNF)-${\alpha}$ mRNA expression and production. Because NO and TNF-${\alpha}$ play an important role in the immune function and host defense, HRG treatment can modulate several aspects of the host defense mechanisms as a result of the stimulations of the inducible nitric oxide synthase and NF-${\kappa}B$. In conclusion, our findings demonstrate that HRG increases the productions of NO and TNF-${\alpha}$ from rIFN-${\gamma}$-primed macrophages and suggest that Rip2/IKK-${\beta}$ plays a critical role in mediating these immune regulatory effects of HRG.

Keywords

References

  1. An HJ, Seo MJ, Choi IY, Park RK, Jeoug S, Lee JY, Kim HM, Um JY, Hong SH. Induction of nitric oxide & tumour necrosis factor-alpha by Psoralea corylifolia. Indian J Med Res. 2008;128:752-758.
  2. Baldwin AS Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev lmmunol. 1996;14:649-683. https://doi.org/10.1146/annurev.immunol.14.1.649
  3. Choi HS, Kim KH, Sohn E, Park JD, Kim BO, Moon EY, Rhee DK, Pyo S. Red ginseng acidic polysaccharide (RGAP) in combination with IFN-ganuna results in enhanced macrophage function through activation of the NF -kappaB pathway. Biosci Biotechnol Biochem. 2008;72:1817-1825. https://doi.org/10.1271/bbb.80085
  4. Chung HS, An HJ, Jeong HJ, Won JH, Hong SH, Kim HM. Water extract isolated from Chelidonium majus enhances nitric oxide and tumour necrosis factor-alpha production via nuclear factor-kappaB activation in mouse peritoneal macrophages. J Pharm Pharmacol. 2004;56:129-134. https://doi.org/10.1211/0022357022467
  5. Fontanini D, Jones BL. Study of metallopeptidase isozyrnes from malted barley (Hordeum vulgare cv.Morex). J Agr Food Chem. 2001;49:4903-4911. https://doi.org/10.1021/jf0104331
  6. Gantt KR, Goldman TL, McCormick ML, Miller MA, Jeronimo SM, Nascimento ET, Britigan BE, Wilson ME. Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi. J Immunol. 2001;167:893-901. https://doi.org/10.4049/jimmunol.167.2.893
  7. Ghosh S, May MJ, Kopp EB. NF-kB and ReI proteins: evolutionarily conserved mediators of immune responses. Ann Rev immunol. 1998;16:225-260. https://doi.org/10.1146/annurev.immunol.16.1.225
  8. Gorjanovic S, Cvetkovic A, Suznjevic D, Beljanski M, Vrvic M, Hranisavljevic J. Isolation and characterization of highly liganded protein from brewer's barley grain. Biosci Biotech Bioch. 2002;66:1940-1944. https://doi.org/10.1271/bbb.66.1940
  9. Ha DC, Lee JW, Ryu GH. Change in ginsenosides andmaltol in dried rawginseng during extrusion process. Food Sci Biotechnol. 2005;14:363-367.
  10. Inohara N, del Peso L, Koseki T, Chen S, Nllllez G. RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. J BioI Chem. 1998;273:12296-12300. https://doi.org/10.1074/jbc.273.20.12296
  11. Inohara N, Koseki T, Lin J, del Peso L, Lucas PC, Chen FF, Ogura Y, Nunez G. An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways. J BioI Chem. 2000;275:27823-27831.
  12. Jeong HJ, Hong SH, Lee DJ, Park JH, Kim KS, Kim HM. Role of Ca(2+) on TNF-alpha and IL-6 secretion from RBL-2H3 mast cells. Cell Signal. 2002;14:633-639. https://doi.org/10.1016/S0898-6568(02)00005-0
  13. Joo SS, Won TJ, Kim MS, Lee DI. Hematopietic effect of ginsenoside Rg3 in ICR mouse primary cultures and its application to a biological response modifier. Fitoterapia. 2004;75:337-341. https://doi.org/10.1016/j.fitote.2004.02.008
  14. Karin M. The beginning of the end: IkappaB kinase (IKK) and NF-kappaB activation. J BioI Chem. 1999;274:27339-27342. https://doi.org/10.1074/jbc.274.39.27339
  15. Kim WY, Kim JM, Han SB, Lee SK, Kim ND, Park MK, Kim CK, Park JH. Steaming of ginseng at high temperature enhances biological activity. J Nat Prod. 2000;63: 1702-1704. https://doi.org/10.1021/np990152b
  16. Kobayashi K, Inohara N, Hernandez LD, Galan JE, Nunez G, Janeway CA, Medzhitov R, Flavell RA. RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive lmmune systems. Nature. 2002;416: 194-199. https://doi.org/10.1038/416194a
  17. Lee TK. Radioprotective potential of ginseng. Mutagenesis. 2005;20:237-239. https://doi.org/10.1093/mutage/gei041
  18. Nam KY. The comparative understanding between red ginseng and white ginseng, processed ginseng (Panax ginseng C.A. Meyer). J Ginseng Res. 2005;29:1-18. https://doi.org/10.5142/JGR.2005.29.1.001
  19. Nathan C. Nitric oxide as a secretory product of mammalian cells. Faseb J. 1992;6:3051-3064. https://doi.org/10.1096/fasebj.6.12.1381691
  20. Park JD. Recent studies on the chemical constituents of Korean ginseng (Panax ginseng C.A.Meyer). Korean J Ginseng Sci. 1996;20:389-415.
  21. Park JH, Cha HY, Seo JJ, Hong JT, Han K, Oh KW. Anxiolytic-like effects of ginseng in the elevated plus-maze model: comparison of red ginseng and Sun ginseng. Prog Neuro-Psychoph. 2005;29:895-900. https://doi.org/10.1016/j.pnpbp.2005.04.016
  22. Rhim H, Kim H, Lee DY, Oh TH, Nah SY. Ginseng and ginsenoside Rg3, a newly identified active ingredient of ginseng, modulate Ca2+ channel currents in rat sensory neurons. Eur J Pharmcol. 2002;436:151-158. https://doi.org/10.1016/S0014-2999(01)01613-2
  23. Scherer DC, Brockman JA, Chen Z, Maniatis T, Ballard DW Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination. Proc Natl Acad Sci USA. 1995;92:11259-11263. https://doi.org/10.1073/pnas.92.24.11259
  24. Shin HM, Kim MH, Kim BH, Jung SH, Kim YS, Park HJ, Hong JT, Min KR, Kim Y. Inhibitory action of novel aromatic diamine compound on lipopolysaccharide-induced nuclear translocation of NF-kappaB without affecting IkappaB degradation. FEBS Lett. 2004;571:50-54. https://doi.org/10.1016/j.febslet.2004.06.056
  25. Stewart ML, Slavin JL. Molecular weight of guar gum affects short-chain fatty acid profile in model intestinal fermentation. Mol Nutr Food Res. 2006;50:971-976. https://doi.org/10.1002/mnfr.200600024
  26. Takagu T, Kameda K, Matsuura Y, Sekiya K, Okuda H. Studies on insulin-like substances in Korean red ginseng. Planta Med. 1990;56:27-30. https://doi.org/10.1055/s-2006-960877
  27. Tao H, Yao M, Zou S, Zhao D, Qiu H. Effect of angiogenesis inhibitor Rg3 on the growth and metastasis of gastric cancer in SCID mice. Zhounghua Wai Ke Za Zhi. 2002;40:606-608.
  28. Thanos D, Maniatis T. NF-kB: a lesson in family values. Cell. 1995;80:529-532. https://doi.org/10.1016/0092-8674(95)90506-5
  29. Tian JW, Fu FH, Geng MY, Jiang YT, Yang JX, Jiang WL, Wang CY, Liu K. Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia In rats. Neurosci Lett. 2005;374:92-97. https://doi.org/10.1016/j.neulet.2004.10.030
  30. Yun TK. Experimental and epidemiological evidence on non-organ specific cancer preventive effect of Korean ginseng and identification of active compounds. Mutat Res. 2003;523:63-74. https://doi.org/10.1016/S0027-5107(02)00322-6
  31. Yun TK, Lee YS, Lee YH, Kim SI, Yun HY. Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds. J Korean Med Sci. 2001;16:6-18. https://doi.org/10.3346/jkms.2001.16.S.S6