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조협의 부위에 따른 항산화 전사인자 Nrf2 활성 효과

Identification of the Plant Part of Gleditsia sinensis that Activates Nrf2, an Anti-oxidative Transcription Factor

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초록

The fruit of Gleditsia sinensis has been extensively used as a key ingredient of an herbal remedy for the treatment of various inflammatory diseases in traditional Korean Medicine. However, the reason of using the fruit of G. sinensis for the remedy is unclear. Since Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key anti-inflammatory transcription factor, which is activated by the fruit of G. sinesis, we examined whether other plant parts of G. sinensis are also capable of suppressing inflammatory responses by activating Nrf2. Water extracts of various parts of G. sinensis were prepared and tested for Nrf2 activation by reporter assay and western blot analysis. Our results show that the hull of G. sinensis is the most potent in activating Nrf2. Sequential organic solvent extraction of the hull show that all the fractions had a higher potency in activating Nrf2 than the water extract, albeit differential degrees. The hull originated from Korea in general activated Nrf2 strongly compared to that of China. Chloroform fraction of the hull was further examined, showing that the fraction induced nuclear localization of Nrf2, indicative of activated Nrf2, and Nrf2-dependent gene expression including NAD(P)H dehydrogenase quinone 1 (NQO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and heme oxygenase –1 (HO-1). Therefore, our results show that, among other plant parts examined in this study, the hull of G. sinensis is the most potent, providing the experimental basis for the use of the hull of G. sinensis as an active ingredient for an anti-inflammatory remedy.

Abstract

The fruit of Gleditsia sinensis has been extensively used as a key ingredient of an herbal remedy for the treatment of various inflammatory diseases in traditional Korean Medicine. However, the reason of using the fruit of G. sinensis for the remedy is unclear. Since Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key anti-inflammatory transcription factor, which is activated by the fruit of G. sinesis, we examined whether other plant parts of G. sinensis are also capable of suppressing inflammatory responses by activating Nrf2. Water extracts of various parts of G. sinensis were prepared and tested for Nrf2 activation by reporter assay and western blot analysis. Our results show that the hull of G. sinensis is the most potent in activating Nrf2. Sequential organic solvent extraction of the hull show that all the fractions had a higher potency in activating Nrf2 than the water extract, albeit differential degrees. The hull originated from Korea in general activated Nrf2 strongly compared to that of China. Chloroform fraction of the hull was further examined, showing that the fraction induced nuclear localization of Nrf2, indicative of activated Nrf2, and Nrf2-dependent gene expression including NAD(P)H dehydrogenase quinone 1 (NQO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and heme oxygenase –1 (HO-1). Therefore, our results show that, among other plant parts examined in this study, the hull of G. sinensis is the most potent, providing the experimental basis for the use of the hull of G. sinensis as an active ingredient for an anti-inflammatory remedy.

참고문헌 (37)

  1. Itoh, K., "Regulatory mechanisms of cellular response to oxidative stress", Free Radic Res, 31, pp.319~324 (1999)
  2. Rahman, I., "Regulation of inflammation and redox signaling by dietary polyphenols", Biochem Pharmacol, 72, pp.1439~1452 (2006)
  3. Itoh, K., "An Nrf2", small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements, 1997, pp.236, 313~322
  4. Ishii, T., "Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages", J Biol Chem, 275, pp.16023~16029 (2000)
  5. Cho, H. Y., "Role of Nrf2 in protection against hyperoxic lung injury in mice", Am J Resp Cell Mol, 26, pp.175~182 (2002)
  6. Lugade, A. A., "Nrf2 Regulates Chronic Lung Inflammation and B-Cell Responses to Nontypeable Haemophilus influenzae", Am J Respir Cell Mol Biol, 45(3), pp.557~565 (2011)
  7. Satoh, T., "Redox regulation of neuronal survival by electrophilic compounds", Trends Neurosci, 30, pp.38~45 (2007)
  8. Vargas, M. R., "The Nrf2-ARE cytoprotective pathway in astrocytes", Expert Rev Mol Med, 11, pp.e17~ (2009)
  9. Surh, Y. J., "NF-kappaB and Nrf2 as prime molecular targets for chemoprevention and cytoprotection with anti-inflammatory and antioxidant phytochemicals", Genes & Nutrition, 2(4), pp.313~317 (2008)
  10. Zhang, D.D., "Mechanistic studies of the Nrf2-Keap1 signaling pathway", Drug Metab Rev, 38, pp.769~789 (2006)
  11. Herbology textbook compilation committee, "Herbology", pp.491~ (2008), Younglimsa
  12. Ju, Y.S., "Ungok Herbology", pp.1035~ (2013), Woosuk Press
  13. Literature research institute of Eastern Medicine, "Korean version of Donguibogam", pp.724~ (2007), Bubin
  14. Shin, T. Y., "Inhibitory effect of mast cell-dependent anaphylaxis by Gleditsia sinensis", Arch Pharm Res, 23, pp.401~406 (2000)
  15. Dai, Y., "Antiallergic and anti-inflammatory properties of the ethanolic extract from Gleditsia sinensis", Biol Pharm Bull, 25, pp.1179~1182 (2002)
  16. Chow, L. M. C., "Gleditsia sinensis fruit extract is a potential chemotherapeutic agent in chronic and acute myelogenous leukemia", Oncol Rep, 10, pp.1601~1607 (2003)
  17. Fu, L. J., "Inhibition of experimental allergic rhinitis by the n-butanol fraction from the anomalous fruits of Gleditsia sinensis", Biol Pharm Bull, 26, pp.974~977 (2003)
  18. Dai, Y., "Antiallergic and anti-inflammatory properties of the ethanolic extract from gleditsia sinensis", Biol Pharm Bull, 25, pp.1179~1182 (2002)
  19. Hou, L. F., "Alleviation of Picryl Chloride-Induced Delayed Type Hypersensitivity Reaction by Saponin Fraction of Gleditsia sinensis", Biol Pharm Bull, 29, pp.1056~1059 (2006)
  20. Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation, "Choi, J. Y.", ~, pp.Evid-Based Compl Alt: eCAM, 974713 (2012)
  21. Durackova, Z., "Some current insights into oxidative stress", Physiol Res, 59, pp.459~469 (2010)
  22. Schraufstatter, I., "Oxidant-induced DNA damage of target cells", J Clin Invest, 82, pp.1040~1050 (1988)
  23. Lee, J. M., "An important role of Nrf2–ARE pathway in the cellular defense mechanism", J Biochem Mol Biol, 37, pp.139~143 (2004)
  24. Kang, M. I., "Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes", Proc Natl Acad Sci, 101, pp.2046~2051 (2004)
  25. Padmanabhan, B., "Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer", Mol Cell, 21, pp.689~700 (2006)
  26. Itoh, K., "Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles", Free Radic Biol Med, 36, pp.1208~1213 (2004)
  27. Vodovotz, Y., "Translational systems approaches to the biology of inflammation and healing", Immunopharmacol Immunotoxicol, 32, pp.181~195 (2010)
  28. Kobayashi, A., "Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1", Mol Cell Biol, 26, pp.221~229 (2006)
  29. Tong, K. I., "Keap1 recruits Neh2 through binding to ETGE and DLG motifs: characterization of the two-site molecular recognition model", Mol Cell Biol, 26, pp.2887~2900 (2006)
  30. Yamahara, J., "Biological active principles of the crude drugs. II. Antiulcerogenic and anti-inflammatory actions of the crude drugs containing saponin", Yakugaku Zasshi, 95, pp.1179~1182 (1975)
  31. Dhakshinamoorthy, S., "Antioxidant regulation of genes encoding enzymes that detoxify xenobiotics and carcinogens", Curr Top Cell Regul, 36, pp.201~216 (2000)
  32. Dalton, T. P., "Knockout of the mouse glutamate cysteine ligase catalytic subunit (Gclc) gene: Embryonic lethal when homozygous, and proposed model for moderate glutathione deficiency when heterozygous", Biochem Biophys Res Commun, 279, pp.324~329 (2000)
  33. Pompella, A., "The changing faces of glutathione, a cellular protagonist", Biochem Pharmacol, 66(8), pp.1499~1503 (2003)
  34. Okinaga, S., "Regulation of human heme oxygenase-1 gene expression under thermal stress", Blood, 87, pp.5074~5084 (1996)
  35. Willis, D., "Heme oxygenase: a novel target for the modulation of the inflammatory response", Nat Med, 2, pp.87~90 (1996)
  36. Zhang, D. D., "Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress", Mol Cell Biol, 23, pp.8137~8151 (2003)
  37. Kobayashi, A., "Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1", Mol Cell Biol, 26, pp.221~229 (2006)

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