Advertisement

Inflammation

, Volume 35, Issue 4, pp 1232–1241 | Cite as

Rehmannia glutinosa Suppresses Inflammatory Responses Elicited by Advanced Glycation End Products

  • Gui-Hyun Baek
  • Yong-Suk Jang
  • Seung-Il Jeong
  • Jaeho Cha
  • Myungsoo Joo
  • Sang-Woo Shin
  • Ki-Tae Ha
  • Han-Sol Jeong
Article

Abstract

Fresh rhizome of Rehmannia glutinosa Libosch. (Saeng-jihwang in Korean: SJH) has been prescribed for the treatment of diabetes-associated complications. The purpose of the present study is to investigate the underlying mechanisms of the efficacy of SJH in diabetes-related complications. Decoction was obtained after boiling SJH in water and subsequent lyophilization. The cellular toxicity of SJH was determined by MTT assay. The antioxidant activity of SJH was measured by DPPH and DCFH-DA assays. The effects of SJH on inflammatory responses elicited by AGEs were assessed by western blotting and semi-quantitative RT-PCR analyses. The water extract of SJH had a high free radical scavenging activity in vitro and decreased the level of intracellular ROS in THP-1 cells treated with AGEs. SJH suppressed the expression of pro-inflammatory genes, including TNF-α, MCP-1, IP-10, COX-2, and iNOS; the activation of NF-κB; and the expression of RAGE, a receptor for AGEs, where the expressions of which were induced by AGEs. These results suggest the possibility that SJH can be an alternative therapeutics for diabetes-associated diseases.

KEY WORDS

Rehmannia glutinosa advanced glycation end products THP-1 NF-κB pro-inflammation 

Notes

Acknowledgments

This work was in part supported by a grant from Ministry of Education Science and Technology KGM2250911 (M.J.).

Supplementary material

10753_2012_9433_MOESM1_ESM.doc (142 kb)
Esm. 1 (DOC 142 kb)

REFERENCES

  1. 1.
    Ahmed, N. 2005. Advanced glycation endproducts—role in pathology of diabetic complications. Diabetes Research and Clinical Practice 67: 3–21.PubMedCrossRefGoogle Scholar
  2. 2.
    Bierhaus, A., M.A. Hofmann, R. Ziegler, and P.P. Nawroth. 1998. AGEs and their interaction with AGE-receptors in vascular disease and diabetes mellitus. I. The AGE concept. Cardiovascular Research 37: 586–600.PubMedCrossRefGoogle Scholar
  3. 3.
    Singh, R., A. Barden, T. Mori, and L. Beilin. 2001. Advanced glycation end-products: a review. Diabetologia 44: 129–146.PubMedCrossRefGoogle Scholar
  4. 4.
    Turk, Z., S. Ljubic, N. Turk, and B. Benko. 2001. Detection of autoantibodies against advanced glycation endproducts and AGE-immune complexes in serum of patients with diabetes mellitus. Clinica chimica acta; international journal of clinical chemistry 303: 105–115.PubMedCrossRefGoogle Scholar
  5. 5.
    Yamamoto, Y., I. Kato, T. Doi, H. Yonekura, S. Ohashi, M. Takeuchi, et al. 2001. Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice. The Journal of Clinical Investigation 108: 261–268.PubMedGoogle Scholar
  6. 6.
    Harja, E., D.X. Bu, B.I. Hudson, J.S. Chang, X. Shen, K. Hallam, et al. 2008. Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE-/- mice. The Journal of Clinical Investigation 118: 183–194.PubMedCrossRefGoogle Scholar
  7. 7.
    Forbes, J.M., L.T. Yee, V. Thallas, M. Lassila, R. Candido, K.A. Jandeleit-Dahm, et al. 2004. Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. Diabetes 53: 1813–1823.PubMedCrossRefGoogle Scholar
  8. 8.
    Wada, R., and S. Yagihashi. 2005. Role of advanced glycation end products and their receptors in development of diabetic neuropathy. Annals of the New York Academy of Sciences 1043: 598–604.PubMedCrossRefGoogle Scholar
  9. 9.
    Peyroux, J., and M. Sternberg. 2006. Advanced glycation endproducts (AGEs): pharmacological inhibition in diabetes. Pathologie-Biologie 54: 405–419.PubMedCrossRefGoogle Scholar
  10. 10.
    Fosmark, D.S., P.A. Torjesen, B.K. Kilhovd, T.J. Berg, L. Sandvik, K.F. Hanssen, et al. 2006. Increased serum levels of the specific advanced glycation end product methylglyoxal-derived hydroimidazolone are associated with retinopathy in patients with type 2 diabetes mellitus. Metabolism, Clinical and Experimental 55: 232–236.CrossRefGoogle Scholar
  11. 11.
    Huebschmann, A.G., J.G. Regensteiner, H. Vlassara, and J.E. Reusch. 2006. Diabetes and advanced glycoxidation end products. Diabetes Care 29: 1420–1432.PubMedCrossRefGoogle Scholar
  12. 12.
    Desai, K., and L. Wu. 2007. Methylglyoxal and advanced glycation endproducts: new therapeutic horizons? Recent Patents on Cardiovascular Drug Discovery 2: 89–99.PubMedCrossRefGoogle Scholar
  13. 13.
    Edelstein, D., and M. Brownlee. 1992. Mechanistic studies of advanced glycosylation end product inhibition by aminoguanidine. Diabetes 41: 26–29.PubMedCrossRefGoogle Scholar
  14. 14.
    Nakamura, S., Z. Makita, S. Ishikawa, K. Yasumura, W. Fujii, K. Yanagisawa, et al. 1997. Progression of nephropathy in spontaneous diabetic rats is prevented by OPB-9195, a novel inhibitor of advanced glycation. Diabetes 46: 895–899.PubMedCrossRefGoogle Scholar
  15. 15.
    Doggrell, S.A. 2001. ALT-711 decreases cardiovascular stiffness and has potential in diabetes, hypertension and heart failure. Expert Opinion on Investigational Drugs 10: 981–983.PubMedCrossRefGoogle Scholar
  16. 16.
    Oturai, P.S., M. Christensen, B. Rolin, K.E. Pedersen, S.B. Mortensen, and E. Boel. 2000. Effects of advanced glycation end-product inhibition and cross-link breakage in diabetic rats. Metabolism, Clinical and Experimental 49: 996–1000.CrossRefGoogle Scholar
  17. 17.
    Stitt, A., T.A. Gardiner, N.L. Alderson, P. Canning, N. Frizzell, N. Duffy, et al. 2002. The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes 51: 2826–2832.PubMedCrossRefGoogle Scholar
  18. 18.
    Figarola, J.L., S. Scott, S. Loera, C. Tessler, P. Chu, L. Weiss, et al. 2003. LR-90 a new advanced glycation endproduct inhibitor prevents progression of diabetic nephropathy in streptozotocin-diabetic rats. Diabetologia 46: 1140–1152.PubMedCrossRefGoogle Scholar
  19. 19.
    Huang, W.J., H.S. Niu, M.H. Lin, J.T. Cheng, and F.L. Hsu. 2010. Antihyperglycemic effect of catalpol in streptozotocin-induced diabetic rats. Journal of Natural Products 73: 1170–1172.PubMedCrossRefGoogle Scholar
  20. 20.
    Kubo, M., T. Asano, H. Shiomoto, and H. Matsuda. 1994. Studies on rehmanniae radix. I. Effect of 50% ethanolic extract from steamed and dried rehmanniae radix on hemorheology in arthritic and thrombosic rats. Biological and Pharmaceutical Bulletin 17: 1282–1286.PubMedCrossRefGoogle Scholar
  21. 21.
    Kiho, T., T. Watanabe, K. Nagai, and S. Ukai. 1992. Hypoglycemic activity of polysaccharide fraction from rhizome of Rehmannia glutinosa Libosch. f. hueichingensis Hsiao and the effect on carbohydrate metabolism in normal mouse liver. Yakugaku zasshi: Journal of the Pharmaceutical Society of Japan 112: 393–400.PubMedGoogle Scholar
  22. 22.
    Yokozawa, T., H.Y. Kim, and N. Yamabe. 2004. Amelioration of diabetic nephropathy by dried rehmanniae radix (Di Huang) extract. The American Journal of Chinese Medicine 32: 829–839.PubMedCrossRefGoogle Scholar
  23. 23.
    Kang, D.G., E.J. Sohn, M.K. Moon, Y.M. Lee, and H.S. Lee. 2005. Rehmannia glutinose ameliorates renal function in the ischemia/reperfusion-induced acute renal failure rats. Biological and Pharmaceutical Bulletin 28: 1662–1667.PubMedCrossRefGoogle Scholar
  24. 24.
    Kim, H.M., C.S. An, K.Y. Jung, Y.K. Choo, J.K. Park, and S.Y. Nam. 1999. Rehmannia glutinosa inhibits tumour necrosis factor-alpha and interleukin-1 secretion from mouse astrocytes. Pharmacological research: the official journal of the Italian Pharmacological Society 40: 171–176.CrossRefGoogle Scholar
  25. 25.
    Ashoor, S.H., and J.B. Zent. 1984. Maillard browning of common amino-acids and sugars. Journal of Food Science 49: 1206–1207.CrossRefGoogle Scholar
  26. 26.
    Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65: 55–63.PubMedCrossRefGoogle Scholar
  27. 27.
    Brandwilliams, W., M.E. Cuvelier, and C. Berset. 1995. Use of a free-radical method to evaluate antioxidant activity. Food Sci Technol-Lebensm-Wiss Technol 28: 25–30.Google Scholar
  28. 28.
    Ramasamy, R., S.J. Vannucci, S.S. Yan, K. Herold, S.F. Yan, and A.M. Schmidt. 2005. Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 15: 16R–28R.PubMedCrossRefGoogle Scholar
  29. 29.
    Baeuerle, P.A., and D. Baltimore. 1996. NF-kappa B: ten years after. Cell 87: 13–20.PubMedCrossRefGoogle Scholar
  30. 30.
    Barnes, P.J., and M. Karin. 1997. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. The New England Journal of Medicine 336: 1066–1071.PubMedCrossRefGoogle Scholar
  31. 31.
    May, M.J., and S. Ghosh. 1997. Rel/NF-kappa B and I kappa B proteins: an overview. Seminars in Cancer Biology 8: 63–73.PubMedCrossRefGoogle Scholar
  32. 32.
    Collins, T. 1993. Endothelial nuclear factor-kappa B and the initiation of the atherosclerotic lesion. Laboratory investigation; a journal of technical methods and pathology 68: 499–508.PubMedGoogle Scholar
  33. 33.
    Read, M.A., M.Z. Whitley, A.J. Williams, and T. Collins. 1994. NF-kappa B and I kappa B alpha: an inducible regulatory system in endothelial activation. The Journal of Experimental Medicine 179: 503–512.PubMedCrossRefGoogle Scholar
  34. 34.
    Verma, I.M., J.K. Stevenson, E.M. Schwarz, D. Van Antwerp, and S. Miyamoto. 1995. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes & Development 9: 2723–2735.CrossRefGoogle Scholar
  35. 35.
    Pouliot, M., J. Baillargeon, J.C. Lee, L.G. Cleland, and M.J. James. 1997. Inhibition of prostaglandin endoperoxide synthase-2 expression in stimulated human monocytes by inhibitors of p38 mitogen-activated protein kinase. Journal of Immunology 158: 4930–4937.Google Scholar
  36. 36.
    Zhang, G., and S. Ghosh. 2001. Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. The Journal of Clinical Investigation 107: 13–19.PubMedCrossRefGoogle Scholar
  37. 37.
    Lander, H.M., J.S. Ogiste, R.A. Moss, D. Stern, and A.M. Schmidt. 1995. Advanced glycation endproducts (ages) induce activation of nuclear factor-kappaB (NF-kB) by a signaling mechanism involving p21(ras) and map kinase via the receptor for ages (rage). Circulation 92: 532–532.Google Scholar
  38. 38.
    Schmidt, A.M., O. Hori, R. Cao, S.D. Yan, J. Brett, J.L. Wautier, et al. 1996. RAGE—a novel cellular receptor for advanced glycation end products. Diabetes 45: S77–S80.PubMedCrossRefGoogle Scholar
  39. 39.
    Sousa, M.M., S. Du Yan, D. Stern, and M.J. Saraiva. 2000. Interaction of the receptor for advanced glycation end products (RAGE) with transthyretin triggers nuclear transcription factor kB (NF-kB) activation. Laboratory Investigation 80: 1101–1110.PubMedCrossRefGoogle Scholar
  40. 40.
    Vlassara, H., and M.R. Palace. 2002. Diabetes and advanced glycation endproducts. Journal of Internal Medicine 251: 87–101.PubMedCrossRefGoogle Scholar
  41. 41.
    Brownlee, M. 2005. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54: 1615–1625.PubMedCrossRefGoogle Scholar
  42. 42.
    Yan, S.D., A.M. Schmidt, G.M. Anderson, J.H. Zhang, J. Brett, Y.S. Zou, et al. 1994. Enhanced cellular oxidant stress by the interaction of advanced glycation end-products with their receptors binding-proteins. Journal of Biological Chemistry 269: 9889–9897.PubMedGoogle Scholar
  43. 43.
    Lander, H.M., J.M. Tauras, J.S. Ogiste, O. Hori, R.A. Moss, and A.M. Schmidt. 1997. Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress. Journal of Biological Chemistry 272: 17810–17814.PubMedCrossRefGoogle Scholar
  44. 44.
    Stern, D., S.D. Yan, S.F. Yan, and A.M. Schmidt. 2002. Receptor for advanced glycation endproducts: a multiligand receptor magnifying cell stress in diverse pathologic settings. Advanced Drug Delivery Reviews 54: 1615–1625.PubMedCrossRefGoogle Scholar
  45. 45.
    Yamagishi, S.I., K. Nakamura, T. Matsui, S. Ueda, K. Fukami, and S. Okuda. 2008. Agents that block advanced glycation end product (AGE)-RAGE (receptor for AGEs)-oxidative stress system: a novel therapeutic strategy for diabetic vascular complications. Expert Opinion on Investigational Drugs 17: 983–996.PubMedCrossRefGoogle Scholar
  46. 46.
    Jiang, Y., D.I. Beller, G. Frendl, and D.T. Graves. 1992. Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes. Journal of Immunology 148: 2423–2428.Google Scholar
  47. 47.
    Wakabayashi, Y., Y. Usui, Y. Okunuki, T. Kezuka, M. Takeuchi, H. Goto, et al. 2010. Correlation of vascular endothelial growth factor with chemokines in the vitreous in diabetic retinopathy. Retina 30: 339–344.PubMedCrossRefGoogle Scholar
  48. 48.
    Miura, T., M. Kako, E. Ishihara, M. Usami, H. Yano, K. Tanigawa, et al. 1997. Antidiabetic effect of seishin-kanro-to in KK-Ay mice. Planta Medica 63: 320–322.PubMedCrossRefGoogle Scholar
  49. 49.
    Meng, Q.Y., X.F. Lv, and X.D. Jin. 2008. [Effect of Rehmannia glutinosa Libosch water extraction on gene expression of proinsulin in type 2 diabetes mellitus rats]. Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 31: 397–399.PubMedGoogle Scholar
  50. 50.
    Waisundara, V.Y., M. Huang, A. Hsu, D. Huang, and B.K. Tan. 2008. Characterization of the anti-diabetic and antioxidant effects of Rehmannia glutinosa in streptozotocin-induced diabetic Wistar rats. The American Journal of Chinese Medicine 36: 1083–1104.PubMedCrossRefGoogle Scholar
  51. 51.
    Lee, H.S., S.T. Kim, and D.K. Cho. 1993. Effects of rehmanniae radix water extract on renal function and renin secretion rate in unanesthetized rabbits. The American Journal of Chinese Medicine 21: 179–186.PubMedCrossRefGoogle Scholar
  52. 52.
    Li, S.L., J.Z. Song, C.F. Qiao, Y. Zhou, K. Qian, K.H. Lee, et al. 2010. A novel strategy to rapidly explore potential chemical markers for the discrimination between raw and processed radix rehmanniae by UHPLC-TOFMS with multivariate statistical analysis. Journal of Pharmaceutical and Biomedical Analysis 51: 812–823.PubMedCrossRefGoogle Scholar
  53. 53.
    Huang, W.J., F.S. Niu, M.H. Lin, J.T. Cheng, and F.L. Hsu. 2010. Antihyperglycemic effect of catalpol in streptozotocin-induced diabetic rats. Journal of Natural Products 73: 1170–1172.PubMedCrossRefGoogle Scholar
  54. 54.
    Wang, C.F., D.Q. Li, H.Y. Xue, and B. Hu. 2010. Oral supplementation of catalpol ameliorates diabetic encephalopathy in rats. Brain Research 1307: 158–165.PubMedCrossRefGoogle Scholar
  55. 55.
    Shieh, J.P., K.C. Cheng, H.H. Chung, Y.F. Kerh, C.H. Yeh, and J.T. Cheng. 2011. Plasma glucose lowering mechanisms of catalpol, an active principle from roots of Rehmannia glutinosa, in streptozotocin-induced diabetic rats. Journal of Agricultural and Food Chemistry 59: 3747–3753.PubMedCrossRefGoogle Scholar
  56. 56.
    Tian, Y.Y., L.J. An, L. Jiang, Y.L. Duan, J. Chen, and B. Jiang. 2006. Catalpol protects dopaminergic neurons from LPS-induced neurotoxicity in mesencephalic neuron-glia cultures. Life Sciences 80: 193–199.PubMedCrossRefGoogle Scholar
  57. 57.
    Bi, J., B. Jiang, J.H. Liu, C. Lei, X.L. Zhang, and L.J. An. 2008. Protective effects of catalpol against H2O2-induced oxidative stress in astrocytes primary cultures. Neuroscience Letters 442: 224–227.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Gui-Hyun Baek
    • 1
  • Yong-Suk Jang
    • 1
  • Seung-Il Jeong
    • 2
  • Jaeho Cha
    • 3
  • Myungsoo Joo
    • 4
  • Sang-Woo Shin
    • 4
  • Ki-Tae Ha
    • 4
  • Han-Sol Jeong
    • 4
  1. 1.Department of Molecular BiologyChonbuk National UniversityJeonjuRepublic of Korea
  2. 2.Jeonju Biomaterials InstituteJeonjuRepublic of Korea
  3. 3.Department of Microbiology, College of Natural SciencesPusan National UniversityBusanRepublic of Korea
  4. 4.Division of Applied Medicine, School of Korean MedicinePusan National UniversityYangsanRepublic of Korea

Personalised recommendations