Biomolecules & Therapeutics

  • 제21권6호
  • /
  • Pages.435-441
  • /
  • 2013
  • /
  • 1976-9148(pISSN)
  • /
  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
권호 표지
DOI QR코드

DOI QR Code

Emodin Isolated from Polygoni cuspidati Radix Inhibits TNF-α and IL-6 Release by Blockading NF-κB and MAP Kinase Pathways in Mast Cells Stimulated with PMA Plus A23187

  • 투고 : 2013.09.09
  • 심사 : 2013.10.31
  • 발행 : 2013.11.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Emodin, a naturally occurring anthraquinone derivative isolated from Polygoni cuspidati radix, has several beneficial pharmacologic effects, which include anti-cancer, anti-diabetic, and anti-inflammatory activities. In this study, the authors examined the effect of emodin on the production of proinflammatory cytokines, such as, tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6, in mouse bone marrow-derived mast cells (BMMCs) stimulated with phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187. To investigate the mechanism responsible for the regulation of pro-inflammatory cytokine production by emodin, the authors assessed its effects on the activations of transcriptional factor nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and mitogen-activated protein kinases (MAPKs). Emodin attenuated the nuclear translocation of (NF)-${\kappa}B$ p65 and its DNA-binding activity by reducing the phosphorylation and degradation of $I{\kappa}B{\alpha}$ and the phosphorylation of $I{\kappa}B$ kinase B (IKK). Furthermore, emodin dose-dependently attenuated the phosphorylations of MAPKs, such as, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAP kinase, and the stress-activated protein kinases (SAPK)/c-Jun-N-terminal kinase (JNK). Taken together, the findings of this study suggest that the anti-inflammatory effects of emodin on PMA plus A23187-stimulated BMMCs are mediated via the inhibition of NF-${\kappa}B$ activation and of the MAPK pathway.

키워드

참고문헌

  1. Alisi, A., Pastore, A., Ceccarelli, S., Panera, N., Gnani, D., Bruscalupi, G., Massimi, M., TOZZI, G., Piemonte, F. and Nobili, V. (2012) Emodin prevents intrahepatic fat accumulation, inflammation and redox status imbalance during diet-induced hepatosteatosis in rats. Int. J. Mol. Sci. 13, 2276-2289. https://doi.org/10.3390/ijms13022276
  2. Amit, S. and Ben-neriah, Y. (2003) NF-kappaB activation in cancer: a challenge for ubiquitination-and proteasome-based therapeutic approach. Semin. Cancer Biol. 13, 15-28. https://doi.org/10.1016/S1044-579X(02)00096-2
  3. Azzolina, A., Bongiovanni, A. and Lampiasi, N. (2003) Substance P induces TNF-alpha and IL-6 production through NF kappa B in peritoneal mast cells. Biochim. Biophys. Acta 1643, 75-83. https://doi.org/10.1016/j.bbamcr.2003.09.003
  4. Baldassare, J. J., Bi, Y. and Bellone, C. J. (1999) The role of p38 mitogen-activated protein kinase in IL-1 beta transcription. J. Immunol. 162, 5367-5373.
  5. Barrett, N. A. and Austen, K. F. (2009) Innate cells and T helper 2 cell immunity in airway infl ammation. Immunity 31, 425-437. https://doi.org/10.1016/j.immuni.2009.08.014
  6. Beyaert, R., Cuenda, A., Vanden Berghe, W., Plaisance, S., Lee, J. C., Haegeman, G., Cohen, P. and Fiers, W. (1996) The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor. EMBO J. 15, 1914-1923.
  7. Boudreau, R. T., Hoskin, D. W. and Lin, T. J. (2004) Phosphatase inhibition potentiates IL-6 production by mast cells in response to FcepsilonRI-mediated activation: involvement of p38 MAPK. J. Leukoc. Biol. 76, 1075-1081. https://doi.org/10.1189/jlb.1003498
  8. Chen, Z., Zhang, L., Yi, J., Yang, Z., Zhang, Z. and Li, Z. (2012) Promotion of adiponectin multimerization by emodin: a novel AMPK activator with PPARgamma-agonist activity. J. Cell. Biochem. 113, 3547-3558. https://doi.org/10.1002/jcb.24232
  9. Chu, X., Wei, M., Yang, X., Cao, Q., Xie, X., Guan, M., Wang, D. and Deng, X. (2012) Effects of an anthraquinone derivative from Rheum offi cinale Baill, emodin, on airway responses in a murine model of asthma. Food Chem. Toxicol. 50, 2368-2375. https://doi.org/10.1016/j.fct.2012.03.076
  10. Church, M. K. and Levi-Schaffer, F. (1997) The human mast cell. J. Allergy Clin. Immunol. 99, 155-160. https://doi.org/10.1016/S0091-6749(97)70089-7
  11. Feng, Y., Huang, S. L., Dou, W., Zhang, S., Chen, J. H., Shen, Y., Shen, J. H. and Leng, Y. (2010) Emodin, a natural product, selectively inhibits 11beta-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice. Br. J. Pharmacol. 161, 113-126. https://doi.org/10.1111/j.1476-5381.2010.00826.x
  12. Galli, S. J., Grimbaldeston, M. and Tsai, M. (2008) Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat. Rev. Immunol. 8, 478-486. https://doi.org/10.1038/nri2327
  13. Galli, S. J., Kalesnikoff, J., Grimbaldeston, M. A., Piliponsky, A. M., Williams, C. M. and Tsai, M. (2005) Mast cells as "tunable" effector and immunoregulatory cells: recent advances. Annu. Rev. Immunol. 23, 749-786. https://doi.org/10.1146/annurev.immunol.21.120601.141025
  14. Glushkova, O. V., Parfenyuk, S. B., Khrenov, M. O., Novoselova, T. V., Lunin, S. M., Fesenko, E. E. and Novoselova, E. G. (2013) Inhibitors of TLR-4, NF-kappaB, and SAPK/JNK signaling reduce the toxic effect of lipopolysaccharide on RAW 264.7 cells. J. Immunotoxicol. 10, 133-140. https://doi.org/10.3109/1547691X.2012.700652
  15. Guha, M. and Mackman, N. (2001) LPS induction of gene expression in human monocytes. Cell. Signal. 13, 85-94. https://doi.org/10.1016/S0898-6568(00)00149-2
  16. Guo, X., Gerl, R. E. and Schraner, J. W. (2003) Defining the involvement of p38alpha MAPK in the production of anti-and proinflammatory cytokines using an SB 203580-resistant form of the kinase. J. Biol. Chem. 278, 22237-22242. https://doi.org/10.1074/jbc.M300847200
  17. Han, Y. M., Lee, S. K., Jeong, D. G., Ryu, S. E., Han, D. C., Kim, D. K. and Kwon, B. M. (2012) Emodin inhibits migration and invasion of DLD-1 (PRL-3) cells via inhibition of PRL-3 phosphatase activity. Bioorg. Med. Chem. Lett. 22, 323-326. https://doi.org/10.1016/j.bmcl.2011.11.008
  18. Hayden, M. S. and Ghosh, S. (2004) Signaling to NF-kappaB. Genes. Dev. 18, 2195-2224. https://doi.org/10.1101/gad.1228704
  19. Heo, S. K., Yun, H. J., Park, W. H. and Park, S. D. (2008) Emodin inhibits TNF-alpha-induced human aortic smooth-muscle cell proliferation via caspase-and mitochondrial-dependent apoptosis. J. Cell. Biochem. 105, 70-80. https://doi.org/10.1002/jcb.21805
  20. Hwangbo, K., Zheng, M. S., Kim, Y. J., Im, J. Y., Lee, C. S., Woo, M. H., Jahng, Y., Chang, H. W. and Son, J. K. (2012) Inhibition of DNA topoisomerases I and II of compounds from Reynoutria japonica. Arch. Pharm. Res. 35, 1583-1589. https://doi.org/10.1007/s12272-012-0909-x
  21. Hwang, J. K., Noh, E. M., Moon, S. J., Kim, J. M., Kwon, K. B., Park, B. H., You, Y. O., Hwang, B. M., Kim, H. J., Kim, B. S., Lee, S. J., Kim, J. S. and Lee, Y. R. (2013) Emodin suppresses inflammatory responses and joint destruction in collagen-induced arthritic mice. Rheumatology (Oxford) 52, 1583-1591. https://doi.org/10.1093/rheumatology/ket178
  22. Ishizuka, T., Terada, N., Gerxins, P., Hamelmann, E., Oshiba, A., Fanger, G. R., Johnson, G. L. and Gelfand, E. W. (1997) Mast cell tumor necrosis factor alpha production is regulated by MEK kinases. Proc. Natl. Acad. Sci. U.S.A. 94, 6358-6363. https://doi.org/10.1073/pnas.94.12.6358
  23. Jeong, H. J., Chung, H. S., Lee, B. R., Kim, S. J., Yoo, S. J., Hong, S. H. and Kim, H. M. (2003) Expression of proinflammatory cytokines via HIF-1alpha and NF-kappaB activation on desferrioxaminestimulated HMC-1 cells. Biochem. Biophys. Res. Commun. 306, 805-811. https://doi.org/10.1016/S0006-291X(03)01073-8
  24. Lee, C. H., Kim, S. I., Lee, K. B., Yoo, Y. C., Ryu, S. Y. and Song, K. S. (2003) Neuraminidase inhibitors from Reynoutria elliptica. Arch. Pharm. Res. 26, 367-374. https://doi.org/10.1007/BF02976693
  25. Lee, Y. S., Kang, O. H., Choi, J. G., Oh, Y. C., Keum, J. H., Kim, S. B., Jenong, G. S., Kim, Y. C., Shin, D. W. and Kwon, D. Y. (2010) Synergistic effect of emodin in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. Pharm. Biol. 48, 1285-1290. https://doi.org/10.3109/13880201003770150
  26. Li, Y. Q., Zhang, Z. X., Xu, Y. J., Ni, W., Chen, S. X., Yang, Z. and Ma, D. (2006) N-Acetyl-L-cysteine and pyrrolidine dithiocarbamate inhibited nuclear factor-kappaB activation in alveolar macrophages by different mechanisms. Acta Pharmacol. Sin. 27, 339-346. https://doi.org/10.1111/j.1745-7254.2006.00264.x
  27. Lim, B. O., Lee, J. H., Ko, N. Y., Mun, S. H., Kim, J. W., Kim, D. K., Kim, J. D., Kim, B. K., Kim, H. S., Her, E., Lee, H. Y. and Choi, W. S. (2007) Polygoni cuspidati radix inhibits the activation of Syk kinase in mast cells for antiallergic activity. Exp. Biol. Med. (Maywood) 232, 1425-1431. https://doi.org/10.3181/0705-RM-118
  28. Lin, S. Z., Chen, K. J., Tong, H. F., Jing, H., Li, H. and Zheng, S. S. (2010) Emodin attenuates acute rejection of liver allografts by in hibiting hepatocellular apoptosis and modulating the Th1/Th2 balance in rats. Clin. Exp. Pharmacol. Physiol. 37, 790-794.
  29. Lu, Y., Hwang, S. L., Son, J. K. and Chang, H. W. (2013) Manassantin B isolated from Saururus chinensis inhibits cyclooxygenase-2-dependent prostaglandin D2 generation by blocking fyn-mediated nuclear factor-kappaB and mitogen activated protein kinase pathways in bone marrow derived-mast cells. Biol. Pharm. Bull. 36, 1370-1374. https://doi.org/10.1248/bpb.b13-00146
  30. Lu, Y., Suh, S. J., Li, X., Hwang, S. L., Li, Y., Hwangbo, K., Park, S. J., Murakami, M., Lee, S. H., Jahng, Y., Son, J. K., Kim, C. H. and Chang, H. W. (2012) Citreorosein, a naturally occurring anthraquinone derivative isolated from Polygoni cuspidati radix, attenuates cyclooxygenase-2-dependent prostaglandin D2 generation by blocking Akt and JNK pathways in mouse bone marrow-derived mast cells. Food Chem. Toxicol. 50, 913-919. https://doi.org/10.1016/j.fct.2011.11.046
  31. Lu, Y., Yang, J. H., Li, X., Hwangbo, K., Hwang, S. L., Taketomi, Y., Murakami, M., Chang, Y. C., Kim, C. H., Son, J. K. and Chang, H. W. (2011) Emodin, a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation. Biochem. Pharmacol. 82, 1700-1708. https://doi.org/10.1016/j.bcp.2011.08.022
  32. Meng, G., Liu, Y., Lou, C. and Yang, H. (2010) Emodin suppresses lipopolysaccharide-induced pro-inflammatory responses and NFkappaB activation by disrupting lipid rafts in CD14-negative endothelial cells. Br. J. Pharmacol. 161, 1628-1644. https://doi.org/10.1111/j.1476-5381.2010.00993.x
  33. Metcalfe, D. D., Baram, D. and Mekori, Y. A. (1997) Mast cells. Physiol. Rev. 77, 1033-1079.
  34. Moon, P. D., Jeong, H. J., Kim, S. J., An, H. J., Lee, H. J., Yang, W. M., Park, S. K., Hong, S. H., Kim, H. M. and Um, J. Y. (2007) Use of electroacupuncture at ST36 to inhibit anaphylactic and inflammatory reaction in mice. Neuroimmunomodulation 14, 24-31. https://doi.org/10.1159/000107285
  35. Mukherjee, A. B. and Zhang, Z. (2011) Allergic asthma: infl uence of genetic and environmental factors. J. Biol. Chem. 286, 32883-32889. https://doi.org/10.1074/jbc.R110.197046
  36. Murakami, M., Matsumoto, R., Austen, K. F. and Arm, J. P. (1994) Prostaglandin endoperoxide synthase-1 and-2 couple to different transmembrane stimuli to generate prostaglandin D2 in mouse bone marrow-derived mast cells. J. Biol. Chem. 269, 22269-22275.
  37. Nakae, S., Suto, H., Kakurai, M., Sedgwick, J. D., Tsai, M. and Galli, S. J. (2005) Mast cells enhance T cell activation: Importance of mast cell-derived TNF. Proc. Natl. Acad. Sci. U.S.A. 102, 6467-6472. https://doi.org/10.1073/pnas.0501912102
  38. Peng, Y., Power, M. R., Li, B. and Lin, T. J. (2005) Inhibition of IKK down-regulates antigen+IgE-induced TNF production by mast cells: a role for the IKK-IkappaB-NF-kappaB pathway in IgE-dependent mast cell activation. J. Leukoc. Biol. 77, 975-983. https://doi.org/10.1189/jlb.0204115
  39. Price, M. M., Oskeritzian, C. A., Falanga, Y. T., Harikumar, K. B., Allegood, J. C., Alvarez, S. E., Conrad, D., Ryan, J. J., Milstien, S. and Spiegel, S. (2013) A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent murine model of allergic asthma. J. Allergy Clin. Immunol. 131, 501-511. https://doi.org/10.1016/j.jaci.2012.07.014
  40. Rasheed, Z., Akhtar, N., Anbazhagan, A. N., Ramamurthy, S., Shukla, M. and Haqqi, T. M. (2009) Polyphenol-rich pomegranate fruit extract (POMx) suppresses PMACI-induced expression of pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-kappaB in human KU812 cells. J. Infl amm. (Lond) 6, 1. https://doi.org/10.1186/1476-9255-6-1
  41. Senftleben, U., Cao, Y., Xiao, G., Greten, F. R., Krahn, G., Bonizzi, G., Chen, Y., Hu, Y., Fong, A., Sun, S. C. and Karin, M. (2001) Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 293, 1495-1499. https://doi.org/10.1126/science.1062677
  42. Sigala, I, Zacharatos, P., Toumpanakis, D., Michailidou, T., Noussia, O., Theocharis, S., Roussos, C., Papapetropoulos, A. and Vassilakopoulos, T. (2011) MAPKs and NF-kappaB differentially regulate cytokine expression in the diaphragm in response to resistive breathing: the role of oxidative stress. Am. J. Physiol. Regul. Integr. Comp. Physiol. 300, R1152-1162. https://doi.org/10.1152/ajpregu.00376.2010
  43. Song, P., Kim, J. H., Ghim, J., Yoon, J. H., Lee, A., Kwon, Y., Hyun, H., Moon, H. Y., Choi, H. S., Berggren, P. O., Suh, P. G. and Ryu, S. H. (2013) Emodin regulates glucose utilization by activating AMPactivated protein kinase. J. Biol. Chem. 288, 5732-5742. https://doi.org/10.1074/jbc.M112.441477
  44. Suh, J. and Rabson, A. B. (2004) NF-kappaB activation in human prostate cancer: important mediator or epiphenomenon? J. Cell. Biochem. 91, 100-117. https://doi.org/10.1002/jcb.10729
  45. Takada, Y., Mukhopadhyay, A., Kundu, G. C., Mahabekeshwar, G. H., Singh, S. and Aggarwal, B. B. (2003) Hydrogen peroxide activates NF-kappa B through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation of p65: evidence for the involvement of I kappa B alpha kinase and Syk protein-tyrosine kinase. J. Biol. Chem. 278, 24233-24241. https://doi.org/10.1074/jbc.M212389200
  46. Turner, H. and Cantrell, D. A. (1997) Distinct Ras effector pathways are involved in Fc epsilon R1 regulation of the transcriptional activity of Elk-1 and NFAT in mast cells. J. Exp. Med. 185, 43-53. https://doi.org/10.1084/jem.185.1.43
  47. Tzeng, T. F., Lu, H. J., Liou, S. S., Chang, C. J. and Liu, I. M. (2012) Emodin protects against high-fat diet-induced obesity via regulation of AMP-activated protein kinase pathways in white adipose tissue. Planta Med. 78, 943-950. https://doi.org/10.1055/s-0031-1298626
  48. Wang, W., Zhou, Q., Liu, L. and Zou, K. (2012) Anti-allergic activity of emodin on IgE-mediated activation in RBL-2H3 cells. Pharmacol. Rep. 64, 1216-1222. https://doi.org/10.1016/S1734-1140(12)70917-9
  49. Xu, C., Shen, G., Chen, C., Gelinas, C. and Kong, A. N. (2005) Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells. Oncogene 24, 4486-4495. https://doi.org/10.1038/sj.onc.1208656

피인용 문헌

  1. Protective Effects of Lupeol againstd-Galactosamine and Lipopolysaccharide-Induced Fulminant Hepatic Failure in Mice vol.77, pp.11, 2014, https://doi.org/10.1021/np500296b
  2. Extract of Rhizoma Polygonum cuspidatum reduces early renal podocyte injury in streptozotocin-induced diabetic rats and its active compound emodin inhibits methylglyoxal-mediated glycation of proteins vol.12, pp.4, 2015, https://doi.org/10.3892/mmr.2015.4214
  3. Bofutsushosan ameliorates obesity in mice through modulating PGC-1α expression in brown adipose tissues and inhibiting inflammation in white adipose tissues vol.14, pp.6, 2016, https://doi.org/10.1016/S1875-5364(16)30042-5
  4. Involvement of the nuclear factor-κB signaling pathway in the regulation of CXC chemokine receptor-4 expression in neuroblastoma cells induced by tumor necrosis factor-α vol.35, pp.2, 2015, https://doi.org/10.3892/ijmm.2014.2032
  5. Root of Polygonum cuspidatum extract reduces progression of diabetes-induced mesangial cell dysfunction via inhibition of platelet-derived growth factor-BB (PDGF-BB) and interaction with its receptor in streptozotocin-induced diabetic rats vol.14, pp.1, 2014, https://doi.org/10.1186/1472-6882-14-477
  6. Characterization of pig sperm hyaluronidase and improvement of the digestibility of cumulus cell mass by recombinant pSPAM1 hyaluronidase in an in vitro fertilization assay vol.150, pp.3-4, 2014, https://doi.org/10.1016/j.anireprosci.2014.09.002
  7. Emodin induces apoptosis of concanavalin A-stimulated murine splenocytes vol.25, pp.6, 2016, https://doi.org/10.1007/s10068-016-0260-y
  8. Inhibitory Effects of 1-(5-Benzyl-4-(4-chlorophenyl)-2-methylfuran-3-yl)ethan-1-one on Allergic Inflammatory Responses in Rat Basophilic Leukemia Cells vol.36, pp.8, 2015, https://doi.org/10.1002/bkcs.10411
  9. Emodin Inhibits Migration and Invasion of Human Endometrial Stromal Cells by Facilitating the Mesenchymal–Epithelial Transition Through Targeting ILK vol.23, pp.11, 2016, https://doi.org/10.1177/1933719116645192
  10. San-Huang-Xie-Xin-Tang Constituents Exert Drug-Drug Interaction of Mutual Reinforcement at Both Pharmacodynamics and Pharmacokinetic Level: A Review vol.7, 2016, https://doi.org/10.3389/fphar.2016.00448
  11. Inhibitory Effect of Alpiniae officinarum Rhizoma Extract on Degranulation in RBL-2H3 Cells vol.28, pp.3, 2015, https://doi.org/10.7732/kjpr.2015.28.3.321
  12. Cinnamaldehyde derivatives inhibit degranulation and inflammatory mediator production in rat basophilic leukemia cells vol.38, 2016, https://doi.org/10.1016/j.intimp.2016.06.018
  13. Emodin Inhibition of Influenza A Virus Replication and Influenza Viral Pneumonia via the Nrf2, TLR4, p38/JNK and NF-kappaB Pathways vol.22, pp.10, 2017, https://doi.org/10.3390/molecules22101754
  14. Effects of Newly Synthesized Recombinant Human Amyloid-β Complexes and Poly-Amyloid-β Fibers on Cell Apoptosis and Cognitive Decline vol.27, pp.11, 2017, https://doi.org/10.4014/jmb.1707.07003
  15. A Novel Peptide from Abalone ( Haliotis discus hannai ) to Suppress Metastasis and Vasculogenic Mimicry of Tumor Cells and Enhance Anti-Tumor Effect In Vitro vol.17, pp.4, 2013, https://doi.org/10.3390/md17040244
  16. Cancer cachexia has many symptoms but only one cause: anoxia vol.9, pp.None, 2013, https://doi.org/10.12688/f1000research.22624.1
  17. Trigonelline, An Alkaloid From Leonurus japonicus Houtt., Suppresses Mast Cell Activation and OVA-Induced Allergic Asthma vol.12, pp.None, 2013, https://doi.org/10.3389/fphar.2021.687970
  18. Rhein protects 5/6 nephrectomized rat against renal injury by reducing inflammation via NF-κB signaling vol.53, pp.7, 2013, https://doi.org/10.1007/s11255-020-02739-w
  19. Cyclodextrin as Functional Carrier in Development of Mucoadhesive Tablets Containing Polygoni cuspidati Extract with Potential for Dental Applications vol.13, pp.11, 2013, https://doi.org/10.3390/pharmaceutics13111916
  20. Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents vol.83, pp.None, 2013, https://doi.org/10.1590/1519-6984.243775