Table of Contents Author Guidelines Submit a Manuscript
International Journal of Inflammation
Volume 2018 (2018), Article ID 5023429, 18 pages
https://doi.org/10.1155/2018/5023429
Review Article

Presenting a New Standard Drug Model for Turmeric and Its Prized Extract, Curcumin

Biologic Pharmamedical Research, 688-2397 King George Blvd., White Rock, BC, V4A7E9, Canada

Correspondence should be addressed to Franco Cavaleri; moc.dem-cigoloib@c.ocnarf

Received 27 September 2017; Accepted 6 December 2017; Published 15 January 2018

Academic Editor: Ke-Wu Zeng

Copyright © 2018 Franco Cavaleri. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. F. Tayyem, D. D. Heath, W. K. Al-Delaimy, and C. L. Rock, “Curcumin content of turmeric and curry powders,” Nutrition and Cancer, vol. 55, no. 2, pp. 126–131, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. D. Heath, F. Khwaja, and C. Rock, “Curcumin content of turmeric and curry powders,” Faseb Journal, 2004. View at Google Scholar
  3. A. Kerkeni, N. Behary, A. Perwuelz, and D. Gupta, “Dyeing of woven polyester fabric with curcumin: Effect of dye concentrations and surface pre-activation using air atmospheric plasma and ultraviolet excimer treatment,” Coloration Technology, vol. 128, no. 3, pp. 223–229, 2012. View at Publisher · View at Google Scholar · View at Scopus
  4. M. T. Huang, Y. R. Lou, W. Ma, H. L. Newmark, K. R. Reuhl, and A. H. Conney, “Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon carcinogenesis in mice,” Cancer Research, vol. 54, no. 22, pp. 5841–5847, 1994. View at Google Scholar · View at Scopus
  5. M. Sinha et al., “Study of the mechanism of action of curcumin: an antiulcer agent,” 1975.
  6. B. Chandran and A. Goel, “A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis,” Phytotherapy Research, vol. 26, no. 11, pp. 1719–1725, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. T. N. Patil and M. Srinivasan, “Hypocholesteremic effect of curcumin in induced hypercholesteremic rats.,” Indian Journal of Experimental Biology (IJEB), vol. 9, no. 2, pp. 167–169, 1971. View at Google Scholar · View at Scopus
  8. M. D. Laird, S. Sukumari-Ramesh, A. E. B. Swift, S. E. Meiler, J. R. Vender, and K. M. Dhandapani, “Curcumin attenuates cerebral edema following traumatic brain injury in mice: a possible role for aquaporin-4?” Journal of Neurochemistry, vol. 113, no. 3, pp. 637–648, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. I. Chattopadhyay, K. Biswas, U. Bandyopadhyay, and R. K. Banerjee, “Turmeric and curcumin: biological actions and medicinal applications,” Current Science, vol. 87, no. 1, pp. 44–53, 2004. View at Google Scholar · View at Scopus
  10. C. Elder, “TITLE: Ayurveda for diabetes mellitus: a review of the biomedical literature,” Alternative Therapies in Health and Medicine, vol. 10, no. 1, pp. 44–50, 2004. View at Google Scholar
  11. K. C. Srivastava, A. Bordia, and S. K. Verma, “Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets,” Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 52, no. 4, pp. 223–227, 1995. View at Publisher · View at Google Scholar · View at Scopus
  12. C. Tohda, N. Nakayama, F. Hatanaka, and K. Komatsu, “Comparison of anti-inflammatory activities of six Curcuma rhizomes: a possible curcuminoid-independent pathway mediated by Curcuma phaeocaulis extract,” Evidence-Based Complementary and Alternative Medicine, vol. 3, no. 2, pp. 255–260, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. H. H. P. Cohly, A. Taylor, M. F. Angel, and A. K. Salahudeen, “Effect of turmeric, turmerin and curcumin on H2O2-induced renal epithelial (LLC-PK1) cell injury,” Free Radical Biology & Medicine, vol. 24, no. 1, pp. 49–54, 1998. View at Publisher · View at Google Scholar · View at Scopus
  14. L. Srinivas, V. K. Shalini, and M. Shylaja, “Turmerin: A water soluble antioxidant peptide from turmeric [Curcuma longa],” Archives of Biochemistry and Biophysics, vol. 292, no. 2, pp. 617–623, 1992. View at Publisher · View at Google Scholar · View at Scopus
  15. P. S. Negi, G. K. Jayaprakasha, L. Jagan Mohan Rao, and K. K. Sakariah, “Antibacterial activity of turmeric oil: a byproduct from curcumin manufacture,” Journal of Agricultural and Food Chemistry, vol. 47, no. 10, pp. 4297–4300, 1999. View at Publisher · View at Google Scholar · View at Scopus
  16. B. T. Kurien and R. H. Scofield, “Increasing aqueous solubility of curcumin for improving bioavailability,” Drug Metabolism & Disposition, vol. 36, pp. 1594–1605, 2009. View at Google Scholar
  17. R. L. Thangapazham, A. Sharma, and R. K. Maheshwari, “Multiple molecular targets in cancer chemoprevention by curcumin,” The AAPS Journal, vol. 8, no. 3, pp. E443–E449, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. R. A. Sharma, A. J. Gescher, and W. P. Steward, “Curcumin: the story so far,” European Journal of Cancer, vol. 41, no. 13, pp. 1955–1968, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. F. Payton, P. Sandusky, and W. L. Alworth, “NMR study of the solution structure of curcumin,” Journal of Natural Products, vol. 70, no. 2, pp. 143–146, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Shehzad, F. Wahid, and Y. S. Lee, “Curcumin in cancer chemoprevention: Molecular targets, pharmacokinetics, bioavailability, and clinical trials,” Archiv der Pharmazie, vol. 343, no. 9, pp. 489–499, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. R. K. Maheshwari, A. K. Singh, J. Gaddipati, and R. C. Srimal, “Multiple biological activities of curcumin: a short review,” Life Sciences, vol. 78, no. 18, pp. 2081–2087, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Li, Z. Zhang, D. L. Hill, H. Wang, and R. Zhang, “Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway,” Cancer Research, vol. 67, no. 5, pp. 1988–1996, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. S. M. Plummer, K. A. Holloway, M. M. Manson et al., “Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex,” Oncogene, vol. 18, no. 44, pp. 6013–6020, 1999. View at Publisher · View at Google Scholar · View at Scopus
  24. N. Dhillon, B. B. Aggarwal, R. A. Newman et al., “Phase II trial of curcumin in patients with advanced pancreatic cancer,” Clinical Cancer Research, vol. 14, no. 14, pp. 4491–4499, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. J. S. Jurenka, “Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research,” Alternative Medicine Review, vol. 14, no. 2, pp. 141–153, 2009. View at Google Scholar · View at Scopus
  26. X. Yang, D. P. Thomas, X. Zhang et al., “Curcumin inhibits platelet-derived growth factor-stimulated vascular smooth muscle cell function and injury-induced neointima formation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 1, pp. 85–90, 2006. View at Publisher · View at Google Scholar · View at Scopus
  27. A. Goel, C. R. Boland, and D. P. Chauhan, “Specific inhibition of cyclooxygenase-2 (COX-2) expression by dietary curcumin in HT-29 human colon cancer cells,” Cancer Letters, vol. 172, no. 2, pp. 111–118, 2001. View at Publisher · View at Google Scholar · View at Scopus
  28. J. Epstein, I. R. Sanderson, and T. T. MacDonald, “Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies,” British Journal of Nutrition, vol. 103, no. 11, pp. 1545–1557, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. E. Skrzypczak-Jankun, N. P. McCabe, S. H. Selman, and J. Jankun, “Curcumin inhibits lipoxygenase by binding to its central cavity: theoretical and X-ray evidence.,” International Journal of Molecular Medicine, vol. 6, no. 5, pp. 521–526, 2000. View at Google Scholar · View at Scopus
  30. R. Lin, X. Chen, W. Li, Y. Han, P. Liu, and R. Pi, “Exposure to metal ions regulates mRNA levels of APP and BACE1 in PC12 cells: blockage by curcumin,” Neuroscience Letters, vol. 440, no. 3, pp. 344–347, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Hamaguchi, K. Ono, and M. Yamada, “Curcumin and Alzheimer's disease,” CNS Neuroscience & Therapeutics, vol. 16, no. 5, pp. 285–297, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. X. Zhang, W.-K. Yin, X.-D. Shi, and Y. Li, “Curcumin activates Wnt/β-catenin signaling pathway through inhibiting the activity of GSK-3β in APPswe transfected SY5Y cells,” European Journal of Pharmaceutical Sciences, vol. 42, no. 5, pp. 540–546, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. J.-W. Cho, K.-S. Lee, and C.-W. Kim, “Curcumin attenuates the expression of IL-1β, IL-6, and TNF-α as well as cyclin E in TNF-α-treated HaCaT cells; NF-κB and MAPKs as potential upstream targets,” International Journal of Molecular Medicine, vol. 19, no. 3, pp. 469–474, 2007. View at Google Scholar · View at Scopus
  34. C. Natarajan and J. J. Bright, “Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes,” The Journal of Immunology, vol. 168, no. 12, pp. 6506–6513, 2002. View at Publisher · View at Google Scholar · View at Scopus
  35. J. Epstein, G. Docena, T. T. MacDonald, and I. R. Sanderson, “Curcumin suppresses p38 mitogen-activated protein kinase activation, reduces IL-1β and matrix metalloproteinase-3 and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease,” British Journal of Nutrition, vol. 103, no. 6, pp. 824–832, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. C. B. Larmonier, J. K. Uno, K.-M. Lee et al., “Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice suggest an IL-10-dependent mechanism of protection,” American Journal of Physiology-Gastrointestinal and Liver Physiology, vol. 295, no. 5, pp. G1079–G1091, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. G. Garcea, D. J. L. Jones, R. Singh et al., “Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration,” British Journal of Cancer, vol. 90, no. 5, pp. 1011–1015, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. O. N. Gordon and C. Schneider, “Vanillin and ferulic acid: Not the major degradation products of curcumin,” Trends in Molecular Medicine, vol. 18, no. 7, pp. 361–363, 2012. View at Publisher · View at Google Scholar · View at Scopus
  39. C. Schneider, O. N. Gordon, R. L. Edwards, and P. B. Luis, “Degradation of curcumin: from mechanism to biological implications,” Journal of Agricultural and Food Chemistry, vol. 63, no. 35, pp. 7606–7614, 2015. View at Publisher · View at Google Scholar · View at Scopus
  40. A. Scott, K. M. Khan, J. L. Cook, and V. Duronio, “What is "inflammation"? Are we ready to move beyond Celsus?” British Journal of Sports Medicine, vol. 38, no. 3, pp. 248-249, 2004. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Weidenbusch and H.-J. Anders, “Tissue microenvironments define and get reinforced by macrophage phenotypes in homeostasis or during inflammation, repair and fibrosis,” Journal of Innate Immunity, vol. 4, no. 5-6, pp. 463–477, 2012. View at Publisher · View at Google Scholar · View at Scopus
  42. C. Savoia and E. L. Schiffrin, “Inflammation in hypertension,” Current Opinion in Nephrology and Hypertension, vol. 15, no. 2, pp. 152–158, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. C. J. Boos and G. Y. H. Lip, “Elevated high-sensitive C-reactive protein, large arterial stiffness and atherosclerosis: A relationship between inflammation and hypertension?” Journal of Human Hypertension, vol. 19, no. 7, pp. 511–513, 2005. View at Publisher · View at Google Scholar · View at Scopus
  44. P. A. Zunszain, N. Hepgul, and C. M. Pariante, “Inflammation and depression,” in Behavioral Neurobiology of Depression and Its Treatment, pp. 135–151, Springer, 2013. View at Google Scholar
  45. R. Dantzer, J. C. O'Connor, M. A. Lawson, and K. W. Kelley, “Inflammation-associated depression: from serotonin to kynurenine,” Psychoneuroendocrinology, vol. 36, no. 3, pp. 426–436, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. K. Löbner and M. Füchtenbusch, “Inflammation and diabetes,” MMW - Fortschritte der Medizin, vol. 146, no. 35-36, pp. 32–36, 2004. View at Google Scholar · View at Scopus
  47. P. Trayhurn and I. S. Wood, “Signalling role of adipose tissue: adipokines and inflammation in obesity,” Biochemical Society Transactions, vol. 33, no. 5, pp. 1078–1081, 2005. View at Publisher · View at Google Scholar · View at Scopus
  48. M. C. Arkan, A. L. Hevener, F. R. Greten et al., “IKK-β links inflammation to obesity-induced insulin resistance,” Nature Medicine, vol. 11, no. 2, pp. 191–198, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. Y.-H. Lee and R. E. Pratley, “The evolving role of inflammation in obesity and the metabolic syndrome,” Current Diabetes Reports, vol. 5, no. 1, pp. 70–75, 2005. View at Publisher · View at Google Scholar · View at Scopus
  50. H. Zhong, M. J. May, E. Jimi, and S. Ghosh, “The phosphorylation status of nuclear NF-κB determines its association with CBP/p300 or HDAC-1,” Molecular Cell, vol. 9, no. 3, pp. 625–636, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. F. Emmerich, M. Meiser, M. Hummel et al., “Overexpression of I kappa B alpha without inhibition of NF-κB activity and mutations in the I kappa B alpha gene in Reed-Sternberg cells,” Blood, vol. 94, no. 9, pp. 3129–3134, 1999. View at Google Scholar · View at Scopus
  52. B. Beutler, K. Hoebe, X. Du, E. Janssen, P. Georgel, and K. Tabeta, “Lps2 and signal transduction in sepsis: at the intersection of host responses to bacteria and viruses,” Scandinavian Journal of Infectious Diseases, vol. 35, no. 9, pp. 563–567, 2003. View at Google Scholar
  53. R. W. O'Rourke, “Molecular mechanisms of obesity and diabetes: At the intersection of weight regulation, inflammation, and glucose homeostasis,” World Journal of Surgery, vol. 33, no. 10, pp. 2007–2013, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Hiscott, H. Kwon, and P. Génin, “Hostile takeovers: Viral appropriation of the NF-κB pathway,” The Journal of Clinical Investigation, vol. 107, no. 2, pp. 143–151, 2001. View at Publisher · View at Google Scholar · View at Scopus
  55. P. A. Baeuerle and T. Henkel, “Function and activation of NF-κB in the immune system,” Annual Review of Immunology, vol. 12, pp. 141–179, 1994. View at Publisher · View at Google Scholar · View at Scopus
  56. E. Tapia, V. Soto, K. M. Ortiz-Vega et al., “Curcumin induces Nrf2 nuclear translocation and prevents glomerular hypertension, hyperfiltration, oxidant stress, and the decrease in antioxidant enzymes in 5/6 nephrectomized rats,” Oxidative Medicine and Cellular Longevity, vol. 2012, Article ID 269039, 14 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  57. R. Bargou, C. Leng, D. Krappmann et al., “High-level nuclear NF-kappa B and Oct-2 is a common feature of cultured Hodgkin/Reed-Sternberg cells,” Blood, vol. 87, no. 10, pp. 4340–4347, 1996. View at Google Scholar
  58. I. M. Verma, J. K. Stevenson, E. M. Schwarz, D. Van Antwerp, and S. Miyamoto, “Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation,” Genes & Development, vol. 9, no. 22, pp. 2723–2735, 1995. View at Google Scholar
  59. E. J. Duh, W. J. Maury, T. M. Folks, A. S. Fauci, and A. B. Rabson, “Tumor necrosis factor α activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-κB sites in the long terminal repeat,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 86, no. 15, pp. 5974–5978, 1989. View at Publisher · View at Google Scholar · View at Scopus
  60. H. L. Pahl, “Activators and target genes of Rel/NF-kappaB transcription factors,” Oncogene, vol. 18, no. 49, pp. 6853–6866, 1999. View at Publisher · View at Google Scholar · View at Scopus
  61. D. G. Franco and R. P. Markus, “The cellular state determines the effect of melatonin on the survival of mixed cerebellar cell culture,” PLoS ONE, vol. 9, no. 9, Article ID e106332, 2014. View at Publisher · View at Google Scholar · View at Scopus
  62. W. Xiao, “Advances in NF-kappaB signaling transduction and transcription,” Cellular & Molecular Immunology, vol. 1, no. 6, pp. 425–435, 2004. View at Google Scholar
  63. B. Kaltschmidt, D. Widera, and C. Kaltschmidt, “Signaling via NF-κB in the nervous system,” Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, vol. 1745, no. 3, pp. 287–299, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. R. Schreck, P. Rieber, and P. A. Baeuerle, “Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-κB transcription factor and HIV-1,” EMBO Journal, vol. 10, no. 8, pp. 2247–2258, 1991. View at Google Scholar · View at Scopus
  65. D.-Y. Lu, C.-H. Tang, W.-L. Yeh et al., “SDF-1alpha up-regulates interleukin-6 through CXCR4, PI3K/Akt, ERK, and NF-kappaB-dependent pathway in microglia,” European Journal of Pharmacology, vol. 613, no. 1–3, pp. 146–154, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. B. Stein and M. X. Yang, “Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-κB and C/EBPβ,” Molecular & Cellular Biology, vol. 15, no. 9, pp. 4971–4979, 1995. View at Publisher · View at Google Scholar · View at Scopus
  67. T. Matsusaka, K. Fujikawa, Y. Nishio et al., “Transcription factors NF-IL6 and NF-κB synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 90, no. 21, pp. 10193–10197, 1993. View at Publisher · View at Google Scholar · View at Scopus
  68. S. Appel, V. Mirakaj, A. Bringmann, M. M. Weck, F. Grünebach, and P. Brossart, “PPAR-γ agonists inhibit toll-like receptor-mediated activation of dendritic cells via the MAP kinase and NF-κB pathways,” Blood, vol. 106, no. 12, pp. 3888–3894, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. M. A. El Gazzar, R. El Mezayen, M. R. Nicolls, and S. C. Dreskin, “Thymoquinone attenuates proinflammatory responses in lipopolysaccharide-activated mast cells by modulating NF-kappaB nuclear transactivation,” Biochimica et Biophysica Acta (BBA) - General Subjects, vol. 1770, no. 4, pp. 556–564, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. T. A. Bird, K. Schooley, S. K. Dower, H. Hagen, and G. D. Virca, “Activation of nuclear transcription factor NF-κB by interleukin-1 is accompanied by casein kinase II-mediated phosphorylation of the p65 subunit,” The Journal of Biological Chemistry, vol. 272, no. 51, pp. 32606–32612, 1997. View at Publisher · View at Google Scholar · View at Scopus
  71. M. J. Suto and A. M. Manning, “Inhibition of NF-кB,” in High Throughput Screening for Novel Anti-Inflammatories, pp. 193–204, Springer, 2000. View at Google Scholar
  72. M. Karin, “How NF-κB is activated: the role of the IκB kinase (IKK) complex,” Oncogene, vol. 18, no. 49, pp. 6867–6874, 1999. View at Publisher · View at Google Scholar · View at Scopus
  73. L. Ling, Z. Cao, and D. V. Goeddel, “Nf-κB-inducing kinase activates IKK-α by phosphorylation of Ser-176,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 95, no. 7, pp. 3792–3797, 1998. View at Publisher · View at Google Scholar · View at Scopus
  74. D.-F. Lee and M.-C. Hung, “Advances in targeting IKK and IKK-related kinases for cancer therapy,” Clinical Cancer Research, vol. 14, no. 18, pp. 5656–5662, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Karin, Y. Yamamoto, and Q. M. Wang, “The IKK NF-κB system: a treasure trove for drug development,” Nature Reviews Drug Discovery, vol. 3, no. 1, pp. 17–26, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. K. Clark, M. Peggie, L. Plater et al., “Novel cross-talk within the IKK family controls innate immunity,” Biochemical Journal, vol. 434, no. 1, pp. 93–104, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. A. Hoffmann, A. Levchenko, M. L. Scott, and D. Baltimore, “The IκB-NF-κB signaling module: temporal control and selective gene activation,” Science, vol. 298, no. 5596, pp. 1241–1245, 2002. View at Publisher · View at Google Scholar · View at Scopus
  78. R. Eric Davis, K. D. Brown, U. Siebenlist, and L. M. Staudt, “Constitutive nuclear factor κB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells,” The Journal of Experimental Medicine, vol. 194, no. 12, pp. 1861–1874, 2001. View at Publisher · View at Google Scholar · View at Scopus
  79. P. F. Gomez, M. H. Pillinger, M. Attur et al., “Resolution of inflammation: Prostaglandin E2 dissociates nuclear trafficking of individual NF-κB subunits (p65, p50) in stimulated rheumatoid synovial fibroblasts,” The Journal of Immunology, vol. 175, no. 10, pp. 6924–6930, 2005. View at Publisher · View at Google Scholar · View at Scopus
  80. Y.-Q. Chen, S. Ghosh, and G. Ghosh, “A novel DNA recognition mode by the NF-κb p65 homodimer,” Nature Structural & Molecular Biology, vol. 5, no. 1, pp. 67–73, 1998. View at Publisher · View at Google Scholar · View at Scopus
  81. T. Fujita, G. P. Nolan, S. Ghosh, and D. Baltimore, “Independent modes of transcriptional activation by the p50 and p65 subunits of NF-kappa B,” Genes & Development, vol. 6, no. 5, pp. 775–787, 1992. View at Google Scholar
  82. C. Kunsch, S. M. Ruben, and C. A. Rosen, “Selection of optimal κB/Rel DNA-binding motifs: Interaction of both subunits of NF-κB with DNA is required for transcriptional activation,” Molecular and Cellular Biology, vol. 12, no. 10, pp. 4412–4421, 1992. View at Publisher · View at Google Scholar · View at Scopus
  83. C. Y. Sasaki, T. J. Barberi, P. Ghosh, and D. L. Longo, “Phosphorylation of RelA/p65 on serine 536 defines an IκBα-independent NF-κB pathway,” The Journal of Biological Chemistry, vol. 280, no. 41, pp. 34538–34547, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. J. Anrather, G. Racchumi, and C. Iadecola, “cis-Acting element-specific transcriptional activity of differentially phosphorylated nuclear factor-κB,” The Journal of Biological Chemistry, vol. 280, no. 1, pp. 244–252, 2005. View at Publisher · View at Google Scholar · View at Scopus
  85. M. L. Schmitz, I. Mattioli, H. Buss, and M. Kracht, “NF-κB: A multifaceted transcription factor regulated at several levels,” ChemBioChem, vol. 5, no. 10, pp. 1348–1358, 2004. View at Publisher · View at Google Scholar · View at Scopus
  86. H. Sakurai, H. Chiba, H. Miyoshi, T. Sugita, and W. Toriumi, “IκB kinases phosphorylate NF-κB p65 subunit on serine 536 in the transactivation domain,” The Journal of Biological Chemistry, vol. 274, no. 43, pp. 30353–30356, 1999. View at Publisher · View at Google Scholar · View at Scopus
  87. D. Wang and A. S. Baldwin Jr., “Activation of nuclear factor-κB-dependent transcription by tumor necrosis factor-α is mediated through phosphorylation of RelA/p65 on serine 529,” The Journal of Biological Chemistry, vol. 273, no. 45, pp. 29411–29416, 1998. View at Publisher · View at Google Scholar · View at Scopus
  88. N. Sizemore, S. Leung, and G. R. Stark, “Activation of phosphatidylinositol 3-kinase in response to interleukin- 1 leads to phosphorylation and activation of the NF-κB p65/RelA subunit,” Molecular and Cellular Biology, vol. 19, no. 7, pp. 4798–4805, 1999. View at Publisher · View at Google Scholar · View at Scopus
  89. S. Ryan, W. T. McNicholas, and C. T. Taylor, “A critical role for p38 map kinase in NF-κB signaling during intermittent hypoxia/reoxygenation,” Biochemical and Biophysical Research Communications, vol. 355, no. 3, pp. 728–733, 2007. View at Publisher · View at Google Scholar · View at Scopus
  90. S. T. Smale, “Hierarchies of NF-κB target-gene regulation,” Nature Immunology, vol. 12, no. 8, pp. 689–694, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. Y.-H. Son, Y.-T. Jeong, K.-A. Lee et al., “Roles of MAPK and NF-κB in interleukin-6 induction by lipopolysaccharide in vascular smooth muscle cells,” Journal of Cardiovascular Pharmacology, vol. 51, no. 1, pp. 71–77, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. P. Delerive, P. Gervois, J.-C. Fruchart, and B. Staels, “Induction of IκBα expression as a mechanism contributing to the anti-inflammatory activities of peroxisome proliferator-activated receptor-α activators,” The Journal of Biological Chemistry, vol. 275, no. 47, pp. 36703–36707, 2000. View at Publisher · View at Google Scholar · View at Scopus
  93. X. Jiang, N. Takahashi, K. Ando, T. Otsuka, T. Tetsuka, and T. Okamoto, “NF-κB p65 transactivation domain is involved in the NF-κB-inducing kinase pathway,” Biochemical and Biophysical Research Communications, vol. 301, no. 2, pp. 583–590, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. N. D. Perkins, N. L. Edwards, C. S. Duckett, A. B. Agranoff, R. M. Schmid, and G. J. Nabel, “A cooperative interaction between NF-kappa B and Sp1 is required for HIV-1 enhancer activation,” EMBO Journal, vol. 12, no. 9, pp. 3551–3558, 1993. View at Google Scholar · View at Scopus
  95. A. D. Yurochko, T. F. Kowalik, S. M. Huong, and E. S. Huang, “Human cytomegalovirus upregulates NF-kappa B activity by transactivating the NF-kappa B p105/p50 and p65 promoters,” Journal of Virology, vol. 69, no. 9, pp. 5391–5400, 1995. View at Google Scholar
  96. L. I. McKay and J. A. Cidlowski, “CBP (CREB binding protein) integrates NF-κB (nuclear factor-κB) and glucocorticoid receptor physical interactions and antagonism,” Molecular Endocrinology, vol. 14, no. 8, pp. 1222–1234, 2000. View at Publisher · View at Google Scholar · View at Scopus
  97. D. B. Starr and D. K. Hawley, “TFIID binds in the minor groove of the TATA box,” Cell, vol. 67, no. 6, pp. 1231–1240, 1991. View at Publisher · View at Google Scholar · View at Scopus
  98. R. Drapkin, A. Merino, and D. Reinberg, “Regulation of RNA polymerase II transcription,” Current Opinion in Cell Biology, vol. 5, no. 3, pp. 469–476, 1993. View at Publisher · View at Google Scholar · View at Scopus
  99. Y. Yumi, U. N. Verma, S. Prajapati, K. Youn-Tae, and R. B. Gaynor, “Histone H3 phosphorylation by ikk-α is critical for cytokine-induced gene expression,” Nature, vol. 423, no. 6940, pp. 655–659, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. G. D. Bren, N. J. Solan, H. Miyoshi, K. N. Pennington, L. J. Pobst, and C. V. Paya, “Transcription of the RelB gene is regulated by NF-κB,” Oncogene, vol. 20, no. 53, pp. 7722–7733, 2001. View at Publisher · View at Google Scholar · View at Scopus
  101. Y. Lavrovsky, B. Chatterjee, R. A. Clark, and A. K. Roy, “Role of redox-regulated transcription factors in inflammation, aging and age-related diseases,” Experimental Gerontology, vol. 35, no. 5, pp. 521–532, 2000. View at Publisher · View at Google Scholar · View at Scopus
  102. N. D. Perkins, “Integrating cell-signalling pathways with NF-κB and IKK function,” Nature Reviews Molecular Cell Biology, vol. 8, no. 1, pp. 49–62, 2007. View at Publisher · View at Google Scholar · View at Scopus
  103. M. Woo, S. Jung, S. Kim et al., “Curcumin suppresses phorbol ester-induced matrix metalloproteinase-9 expression by inhibiting the PKC to MAPK signaling pathways in human astroglioma cells,” Biochemical and Biophysical Research Communications, vol. 335, no. 4, pp. 1017–1025, 2005. View at Publisher · View at Google Scholar · View at Scopus
  104. S. Singh and B. B. Aggarwal, “Activation of transcription factor NF-κB is suppressed by curcumin (diferuloylmethane),” The Journal of Biological Chemistry, vol. 270, no. 42, pp. 24995–25000, 1995. View at Google Scholar
  105. L. Vermeulen, G. De Wilde, P. Van Damme, W. V. Berghe, and G. Haegeman, “Transcriptional activation of the NF-κB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1),” EMBO Journal, vol. 22, no. 6, pp. 1313–1324, 2003. View at Publisher · View at Google Scholar · View at Scopus
  106. G. Pearson, F. Robinson, T. B. Gibson et al., “Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions,” Endocrine Reviews, vol. 22, no. 2, pp. 153–183, 2001. View at Publisher · View at Google Scholar · View at Scopus
  107. G.-Y. Kim, K.-H. Kim, S.-H. Lee et al., “Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and translocation of NF-κB as potential targets,” The Journal of Immunology, vol. 174, no. 12, pp. 8116–8124, 2005. View at Publisher · View at Google Scholar · View at Scopus
  108. D. G. Binion, M. F. Otterson, and P. Rafiee, “Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition,” Gut, vol. 57, no. 11, pp. 1509–1517, 2008. View at Publisher · View at Google Scholar · View at Scopus
  109. D. G. Adams, R. L. Coffee Jr., H. Zhang, S. Pelech, S. Strack, and B. E. Wadzinski, “Positive regulation of Raf1-MEK1/2-ERK1/2 signaling by protein serine/threonine phosphatase 2A holoenzymes,” The Journal of Biological Chemistry, vol. 280, no. 52, pp. 42644–42654, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. G. L. Johnson and R. Lapadat, “Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases,” Science, vol. 298, no. 5600, pp. 1911-1912, 2002. View at Publisher · View at Google Scholar · View at Scopus
  111. A. Carracedo, L. Ma, and J. Teruya-Feldstein, “Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer,” The Journal of Clinical Investigation, vol. 118, no. 9, pp. 3065–3074, 2008. View at Publisher · View at Google Scholar · View at Scopus
  112. W. E. Tidyman and K. A. Rauen, “The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation,” Current Opinion in Genetics & Development, vol. 19, no. 3, pp. 230–236, 2009. View at Publisher · View at Google Scholar · View at Scopus
  113. K. F. Chung, “p38 mitogen-activated protein kinase pathways in asthma and COPD,” CHEST, vol. 139, no. 6, pp. 1470–1479, 2011. View at Publisher · View at Google Scholar · View at Scopus
  114. S. Matthiesen, A. Bahulayan, O. Holz, and K. Racké, “MAPK pathway mediates muscarinic receptor-induced human lung fibroblast proliferation,” Life Sciences, vol. 80, no. 24-25, pp. 2259–2262, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. M. R. Junttila, S.-P. Li, and J. Westermarck, “Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival,” The FASEB Journal, vol. 22, no. 4, pp. 954–965, 2008. View at Publisher · View at Google Scholar · View at Scopus
  116. A. Bonni, A. Brunet, A. E. West, S. R. Datta, M. A. Takasu, and M. E. Greenberg, “Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms,” Science, vol. 286, no. 5443, pp. 1358–1362, 1999. View at Publisher · View at Google Scholar · View at Scopus
  117. T. Okazaki, S. Sakon, T. Sasazuki et al., “Phosphorylation of serine 276 is essential for p65 NF-κB subunit-dependent cellular responses,” Biochemical and Biophysical Research Communications, vol. 300, no. 4, pp. 807–812, 2003. View at Publisher · View at Google Scholar · View at Scopus
  118. A. S. Baldwin Jr., “The NF-κB and IκB proteins: new discoveries and insights,” Annual Review of Immunology, vol. 14, pp. 649–683, 1996. View at Publisher · View at Google Scholar · View at Scopus
  119. P. Viatour, M. Merville, V. Bours, and A. Chariot, “Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation,” Trends in Biochemical Sciences, vol. 30, no. 1, pp. 43–52, 2005. View at Publisher · View at Google Scholar · View at Scopus
  120. F. Chang, L. S. Steelman, J. T. Lee et al., “Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: Potential targeting for therapeutic intervention,” Leukemia, vol. 17, no. 7, pp. 1263–1293, 2003. View at Publisher · View at Google Scholar · View at Scopus
  121. A. Oeckinghaus, M. S. Hayden, and S. Ghosh, “Crosstalk in NF-κB signaling pathways,” Nature Immunology, vol. 12, no. 8, pp. 695–708, 2011. View at Publisher · View at Google Scholar · View at Scopus
  122. H. F. Kramer and L. J. Goodyear, “Exercise, MAPK, and NF-κB signaling in skeletal muscle,” Journal of Applied Physiology, vol. 103, no. 1, pp. 388–395, 2007. View at Publisher · View at Google Scholar · View at Scopus
  123. W. Min, Z. W. Bin, Z. B. Quan, Z. J. Hui, and F. G. Sheng, “The signal transduction pathway of PKC/NF-κB/c-fos may be involved in the influence of high glucose on the cardiomyocytes of neonatal rats,” Cardiovascular Diabetology, vol. 8, article 8, 2009. View at Publisher · View at Google Scholar · View at Scopus
  124. M. L. Schmitz, M. A. Dos Santos Silva, and P. A. Baeuerle, “Transactivation domain 2 (TA2) of p65 NF-κB. Similarity to TA1 and phorbol ester-stimulated activity and phosphorylation in intact cells,” The Journal of Biological Chemistry, vol. 270, no. 26, pp. 15576–15584, 1995. View at Publisher · View at Google Scholar · View at Scopus
  125. H. Zhong, R. E. Voll, and S. Ghosh, “Phosphorylation of NF-κB p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300,” Molecular Cell, vol. 1, no. 5, pp. 661–671, 1998. View at Publisher · View at Google Scholar · View at Scopus
  126. J. Xing, D. D. Ginty, and M. E. Greenberg, “Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase,” Science, vol. 273, no. 5277, pp. 959–963, 1996. View at Publisher · View at Google Scholar · View at Scopus
  127. M. Deak, A. D. Clifton, J. M. Lucocq, and D. R. Alessi, “Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB,” EMBO Journal, vol. 17, no. 15, pp. 4426–4441, 1998. View at Publisher · View at Google Scholar · View at Scopus
  128. D. Chauhan, H. Uchiyama, Y. Akbarali et al., “Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B,” Blood, vol. 3, pp. 1104–1112, 87. View at Google Scholar
  129. M. Karin and A. Lin, “NF-κB at the crossroads of life and death,” Nature Immunology, vol. 3, no. 3, pp. 221–227, 2002. View at Publisher · View at Google Scholar · View at Scopus
  130. J. J. Wu and A. M. Bennett, “Essential role for mitogen-activated protein (MAP) kinase phosphatase-1 in stress-responsive MAP kinase and cell survival signaling,” The Journal of Biological Chemistry, vol. 280, no. 16, pp. 16461–16466, 2005. View at Publisher · View at Google Scholar · View at Scopus
  131. J.-M. Yun, I. Jialal, and S. Devaraj, “Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin,” The Journal of Nutritional Biochemistry, vol. 22, no. 5, pp. 450–458, 2011. View at Publisher · View at Google Scholar · View at Scopus
  132. J. Gao, H. Zhou, T. Lei et al., “Curcumin inhibits renal cyst formation and enlargement in vitro by regulating intracellular signaling pathways,” European Journal of Pharmacology, vol. 654, no. 1, pp. 92–99, 2011. View at Publisher · View at Google Scholar · View at Scopus
  133. Y. Guo, Q. Shan, Y. Gong et al., “Curcumin induces apoptosis via simultaneously targeting AKT/mTOR and RAF/MEK/ERK survival signaling pathways in human leukemia THP-1 cells,” Die Pharmazie-An International Journal of Pharmaceutical Sciences, vol. 69, no. 3, pp. 229–233, 2014. View at Google Scholar
  134. I. Jutooru, G. Chadalapaka, P. Lei, and S. Safe, “Inhibition of NFκB and pancreatic cancer cell and tumor growth by curcumin is dependent on specificity protein down-regulation,” The Journal of Biological Chemistry, vol. 285, no. 33, pp. 25332–25344, 2010. View at Publisher · View at Google Scholar · View at Scopus
  135. F. D'Acquisto, M. J. May, and S. Ghosh, “Inhibition of nuclear factor kappa B (NF-B): an emerging theme in anti-inflammatory therapies.,” Molecular Interventions, vol. 2, no. 1, pp. 22–35, 2002. View at Publisher · View at Google Scholar · View at Scopus
  136. I. Brouet and H. Ohshima, “Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages,” Biochemical and Biophysical Research Communications, vol. 206, no. 2, pp. 533–540, 1995. View at Publisher · View at Google Scholar · View at Scopus
  137. A. C. Bharti, N. Donato, S. Singh, and B. B. Aggarwal, “Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-κB and IκBα kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis,” Blood, vol. 101, no. 3, pp. 1053–1062, 2003. View at Publisher · View at Google Scholar · View at Scopus
  138. S. Shishodia, H. M. Amin, R. Lai, and B. B. Aggarwal, “Curcumin (diferuloylmethane) inhibits constitutive NF-κB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma,” Biochemical Pharmacology, vol. 70, no. 5, pp. 700–713, 2005. View at Publisher · View at Google Scholar · View at Scopus
  139. A. L. Berger, C. O. Randak, L. S. Ostedgaard, P. H. Karp, D. W. Vermeer, and M. J. Welsh, “Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity,” The Journal of Biological Chemistry, vol. 280, no. 7, pp. 5221–5226, 2005. View at Publisher · View at Google Scholar · View at Scopus
  140. F. Zhang, N. K. Altorki, J. R. Mestre, K. Subbaramaiah, and A. J. Dannenberg, “Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells,” Carcinogenesis, vol. 20, no. 3, pp. 445–451, 1999. View at Publisher · View at Google Scholar · View at Scopus
  141. J. Holy, “Curcumin inhibits cell motility and alters microfilament organization and function in prostate cancer cells,” Cell Motility and the Cytoskeleton, vol. 58, no. 4, pp. 253–268, 2004. View at Publisher · View at Google Scholar · View at Scopus
  142. J.-Y. Liu, S.-J. Lin, and J.-K. Lin, “Inhibitory effects of curcumin on protein kinase C activity induced by 12-O-tetradecanoyl-phorbol-13-acetate in MH 3T3 cells,” Carcinogenesis, vol. 14, no. 5, pp. 857–861, 1993. View at Publisher · View at Google Scholar · View at Scopus
  143. Y. Tanaka, M. V. Gavrielides, Y. Mitsuuchi, T. Fujii, and M. G. Kazanietz, “Protein Kinase C Promotes Apoptosis in LNCaP Prostate Cancer Cells through Activation of p38 MAPK and Inhibition of the Akt Survival Pathway,” The Journal of Biological Chemistry, vol. 278, no. 36, pp. 33753–33762, 2003. View at Publisher · View at Google Scholar · View at Scopus
  144. G.-Y. Wu, K. Deisseroth, and R. W. Tsien, “Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology,” Nature Neuroscience, vol. 4, no. 2, pp. 151–158, 2001. View at Publisher · View at Google Scholar · View at Scopus
  145. S. Reddy and B. B. Aggarwal, “Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase,” FEBS Letters, vol. 341, no. 1, pp. 19–22, 1994. View at Publisher · View at Google Scholar · View at Scopus
  146. M. Wang, Y. Ruan, Q. Chen, S. Li, Q. Wang, and J. Cai, “Curcumin induced HepG2 cell apoptosis-associated mitochondrial membrane potential and intracellular free Ca2+ concentration,” European Journal of Pharmacology, vol. 650, no. 1, pp. 41–47, 2011. View at Publisher · View at Google Scholar · View at Scopus
  147. J. A. Bush, K.-J. J. Cheung, and G. Li, “Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53,” Experimental Cell Research, vol. 271, no. 2, pp. 305–314, 2001. View at Publisher · View at Google Scholar · View at Scopus
  148. T. Choudhuri, S. Pal, T. Das, and G. Sa, “Curcumin selectively induces apoptosis in deregulated cyclin D1-expressed cells at G2 phase of cell cycle in a p53-dependent manner,” The Journal of Biological Chemistry, vol. 280, no. 20, pp. 20059–20068, 2005. View at Publisher · View at Google Scholar · View at Scopus
  149. R. J. Anto, A. Mukhopadhyay, K. Denning, and B. B. Aggarwal, “Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl,” Carcinogenesis, vol. 23, no. 1, pp. 143–150, 2002. View at Publisher · View at Google Scholar · View at Scopus
  150. R. Wilken, M. S. Veena, M. B. Wang, and E. S. Srivatsan, “Curcumin: a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma,” Molecular Cancer, vol. 10, article 12, 2011. View at Publisher · View at Google Scholar · View at Scopus
  151. S. Swarnakar, K. Ganguly, P. Kundu, A. Banerjee, P. Maity, and A. V. Sharma, “Curcumin regulates expression and activity of matrix metalloproteinases 9 and 2 during prevention and healing of indomethacin-induced gastric ulcer,” The Journal of Biological Chemistry, vol. 280, no. 10, pp. 9409–9415, 2005. View at Publisher · View at Google Scholar · View at Scopus
  152. C. M. Kaefer and J. A. Milner, “The role of herbs and spices in cancer prevention,” The Journal of Nutritional Biochemistry, vol. 19, no. 6, pp. 347–361, 2008. View at Publisher · View at Google Scholar · View at Scopus
  153. Q. Li and I. M. Verma, “NF-κB regulation in the immune system,” Nature Reviews Immunology, vol. 2, no. 10, pp. 725–734, 2002. View at Publisher · View at Google Scholar · View at Scopus
  154. K.-S. Chun, Y.-S. Keum, S. S. Han, Y.-S. Song, S.-H. Kim, and Y.-J. Surh, “Curcumin inhibits phorbol ester-induced expression of cyclooxygenase-2 in mouse skin through suppression of extracellular signal-regulated kinase activity and NF-κB activation,” Carcinogenesis, vol. 24, no. 9, pp. 1515–1524, 2003. View at Publisher · View at Google Scholar · View at Scopus
  155. C. Jobin, C. A. Bradham, M. P. Russo et al., “Curcumin blocks cytokine-mediated NF-κB activation and proinflammatory gene expression by inhibiting inhibitory factor I-κB kinase activity,” The Journal of Immunology, vol. 163, no. 6, pp. 3474–3483, 1999. View at Google Scholar · View at Scopus
  156. L. Martelli, E. Ragazzi, F. Di Mario et al., “A potential role for the vanilloid receptor TRPV1 in the therapeutic effect of curcumin in dinitrobenzene sulphonic acid-induced colitis in mice,” Neurogastroenterology & Motility, vol. 19, no. 8, pp. 668–674, 2007. View at Publisher · View at Google Scholar · View at Scopus
  157. K. Meghana, G. Sanjeev, and B. Ramesh, “Curcumin prevents streptozotocin-induced islet damage by scavenging free radicals: a prophylactic and protective role,” European Journal of Pharmacology, vol. 577, no. 1–3, pp. 183–191, 2007. View at Publisher · View at Google Scholar · View at Scopus
  158. H.-Y. Hsu, L.-C. Chu, K.-F. Hua, and L. K. Chao, “Heme oxygenase-1 mediates the anti-inflammatory effect of curcumin within LPS-stimulated human monocytes,” Journal of Cellular Physiology, vol. 215, no. 3, pp. 603–612, 2008. View at Publisher · View at Google Scholar · View at Scopus
  159. M. A. El-Moselhy, A. Taye, S. S. Sharkawi, S. F. I. El-Sisi, and A. F. Ahmed, “The antihyperglycemic effect of curcumin in high fat diet fed rats. Role of TNF-α and free fatty acids,” Food and Chemical Toxicology, vol. 49, no. 5, pp. 1129–1140, 2011. View at Publisher · View at Google Scholar · View at Scopus
  160. P. Suresh Babu and K. Srinivasan, “Influence of dietary curcumin and cholesterol on the progression of experimentally induced diabetes in albino rat,” Molecular and Cellular Biochemistry, vol. 152, no. 1, pp. 13–21, 1995. View at Publisher · View at Google Scholar · View at Scopus
  161. L. L. Hurley, L. Akinfiresoye, E. Nwulia, A. Kamiya, A. A. Kulkarni, and Y. Tizabi, “Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF,” Behavioural Brain Research, vol. 239, no. 1, pp. 27–30, 2013. View at Publisher · View at Google Scholar · View at Scopus
  162. J. Sanmukhani, A. Anovadiya, and C. B. Tripathi, “Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: An acute and chronic study,” Acta Poloniae Pharmaceutica. Drug Research, vol. 68, no. 5, pp. 769–775, 2011. View at Google Scholar · View at Scopus
  163. W. Wongcharoen and A. Phrommintikul, “The protective role of curcumin in cardiovascular diseases,” International Journal of Cardiology, vol. 133, no. 2, pp. 145–151, 2009. View at Publisher · View at Google Scholar · View at Scopus
  164. T. Morimoto, Y. Sunagawa, T. Kawamura et al., “The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats,” The Journal of Clinical Investigation, vol. 118, no. 3, pp. 868–878, 2008. View at Publisher · View at Google Scholar · View at Scopus
  165. M. Gharate, “Rheumatoid arthritis & Complementary and Alternative Medicine,” Pharmainfo. net, 5, 2007.
  166. M. E. Egan, M. Pearson, S. A. Weiner et al., “Curcumin, a Major Constituent of Turmeric, Corrects Cystic Fibrosis Defects,” Science, vol. 304, no. 5670, pp. 600–602, 2004. View at Publisher · View at Google Scholar · View at Scopus
  167. G. Allam, “Immunomodulatory effects of curcumin treatment on murine schistosomiasis mansoni,” Immunobiology, vol. 214, no. 8, pp. 712–727, 2009. View at Publisher · View at Google Scholar · View at Scopus
  168. S. Mishra and K. Palanivelu, “The effect of curcumin (turmeric) on Alzheimer's disease: an overview,” Annals of Indian Academy of Neurology, vol. 11, no. 1, pp. 13–19, 2008. View at Publisher · View at Google Scholar · View at Scopus
  169. S. J. Moghaddam, P. Barta, S. G. Mirabolfathinejad et al., “Curcumin inhibits COPD-like airway inflammation and lung cancer progression in mice,” Carcinogenesis, vol. 30, no. 11, pp. 1949–1956, 2009. View at Publisher · View at Google Scholar · View at Scopus
  170. B. B. Aggarwal, “Targeting lammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals,” Annual Review of Nutrition, vol. 30, pp. 173–199, 2010. View at Publisher · View at Google Scholar · View at Scopus
  171. L. Alappat and A. B. Awad, “Curcumin and obesity: evidence and mechanisms,” Nutrition Reviews, vol. 68, no. 12, pp. 729–738, 2010. View at Publisher · View at Google Scholar · View at Scopus
  172. A. Shehzad, T. Ha, F. Subhan, and Y. S. Lee, “New mechanisms and the anti-inflammatory role of curcumin in obesity and obesity-related metabolic diseases,” European Journal of Nutrition, vol. 50, no. 3, pp. 151–161, 2011. View at Publisher · View at Google Scholar · View at Scopus
  173. A. Belkacemi, S. Doggui, L. Dao, and C. Ramassamy, “Challenges associated with curcumin therapy in Alzheimer disease,” Expert Reviews in Molecular Medicine, vol. 13, no. 5, p. e34, 2011. View at Publisher · View at Google Scholar · View at Scopus
  174. H.-J. Seo, S.-M. Wang, C. Han et al., “Curcumin as a putative antidepressant,” Expert Review of Neurotherapeutics, vol. 15, no. 3, pp. 269–280, 2015. View at Publisher · View at Google Scholar · View at Scopus
  175. M. Mall and K. Kunzelmann, “Correction of the CF defect by curcumin: Hypes and disappointments,” BioEssays, vol. 27, no. 1, pp. 9–13, 2005. View at Publisher · View at Google Scholar · View at Scopus
  176. C.-H. Hsu and A.-L. Cheng, “Clinical studies with curcumin,” in The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease, pp. 471–480, Springer, 2007. View at Google Scholar
  177. A. Goel and B. B. Aggarwal, “Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs,” Nutrition and Cancer, vol. 62, no. 7, pp. 919–930, 2010. View at Publisher · View at Google Scholar · View at Scopus
  178. S. Ganta and M. Amiji, “Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells,” Molecular Pharmaceutics, vol. 6, no. 3, pp. 928–939, 2009. View at Publisher · View at Google Scholar · View at Scopus
  179. S.-E. Chuang, P.-Y. Yeh, Y.-S. Lu et al., “Basal levels and patterns of anticancer drug-induced activation of nuclear factor-κB (NF-κB), and its attenuation by tamoxifen, dexamethasone, and curcumin in carcinoma cells,” Biochemical Pharmacology, vol. 63, no. 9, pp. 1709–1716, 2002. View at Publisher · View at Google Scholar · View at Scopus
  180. J. Zhang, T. Zhang, X. Ti et al., “Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway,” Biochemical and Biophysical Research Communications, vol. 399, no. 1, pp. 1–6, 2010. View at Publisher · View at Google Scholar · View at Scopus
  181. P. Venkatesan and M. N. A. Rao, “Structure-activity relationships for the inhibition of lipid peroxidation and the scavenging of free radicals by synthetic symmetrical curcumin analogues,” Journal of Pharmacy and Pharmacology, vol. 52, no. 9, pp. 1123–1128, 2000. View at Publisher · View at Google Scholar · View at Scopus
  182. P. Anand, S. G. Thomas, A. B. Kunnumakkara et al., “Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature,” Biochemical Pharmacology, vol. 76, no. 11, pp. 1590–1611, 2008. View at Publisher · View at Google Scholar · View at Scopus
  183. B.-K. Jadhav, K.-R. Mahadik, and A.-R. Paradkar, “Development and validation of improved reversed phase-HPLC method for simultaneous determination of curcumin, demethoxycurcumin and bis-demethoxycurcumin,” Chromatographia, vol. 65, no. 7-8, pp. 483–488, 2007. View at Publisher · View at Google Scholar · View at Scopus
  184. J. Krasovsky, D. H. Chang, G. Deng et al., “Inhibition of human dendritic cell activation by hydroethanolic but not lipophilic extracts of turmeric (Curcuma longa),” Planta Medica, vol. 75, no. 4, pp. 312–315, 2009. View at Publisher · View at Google Scholar · View at Scopus
  185. V. P. Rodríguez, C. Sweet, B. N. Timmermann, and A. M. Sólyom, “Development of an LC/MS/MS method to separate and analyze curcuminoids, their metabolites and degradation products,” 2004.
  186. M. Marsin Sanagi, U. K. Ahmad, and R. M. Smith, “Application of supercritical fluid extraction and chromatography to the analysis of turmeric,” Journal of Chromatographic Science (JCS), vol. 31, no. 1, pp. 20–25, 1993. View at Publisher · View at Google Scholar · View at Scopus
  187. S. Anuchapreeda, W. Sadjapong, C. Duangrat, and P. Limtrakul, “The cytotoxic effect of curumin, demethoxycurcumin and bisdemethoxycurcumin purified from Turmeric powder on leukemic cell lines,” Bulletin of Chiang Mai Associated Medical Sciences, vol. 39, no. 1, p. 60, 2006. View at Google Scholar
  188. M.-T. Huang, W. Ma, Y.-P. Lu et al., “Effects of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin on 12-Ο-tetradecanoylphorbol-13-acetate-induced tumor promotion,” Carcinogenesis, vol. 16, no. 10, pp. 2493–2497, 1995. View at Publisher · View at Google Scholar · View at Scopus
  189. M. Balasubramanyam, A. A. Koteswari, R. S. Kumar, S. F. Monickaraj, J. U. Maheswari, and V. Mohan, “Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications,” Journal of Biosciences, vol. 28, no. 6, pp. 715–721, 2003. View at Publisher · View at Google Scholar · View at Scopus
  190. V. Soetikno, K. Watanabe, F. R. Sari et al., “Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats,” Molecular Nutrition & Food Research, vol. 55, no. 11, pp. 1655–1665, 2011. View at Publisher · View at Google Scholar · View at Scopus
  191. S. A. Rushworth, R. M. Ogborne, C. A. Charalambos, and M. A. O'Connell, “Role of protein kinase C δ in curcumin-induced antioxidant response element-mediated gene expression in human monocytes,” Biochemical and Biophysical Research Communications, vol. 341, no. 4, pp. 1007–1016, 2006. View at Publisher · View at Google Scholar · View at Scopus
  192. Y. A. Mahmmoud, “Modulation of protein kinase C by curcumin; inhibition and activation switched by calcium ions,” British Journal of Pharmacology, vol. 150, no. 2, pp. 200–208, 2007. View at Publisher · View at Google Scholar · View at Scopus
  193. R. A. Sharma, S. A. Euden, S. L. Platton et al., “Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance,” Clinical Cancer Research, vol. 10, no. 20, pp. 6847–6854, 2004. View at Publisher · View at Google Scholar · View at Scopus
  194. Y.-J. Wang, M.-H. Pan, A.-L. Cheng et al., “Stability of curcumin in buffer solutions and characterization of its degradation products,” Journal of Pharmaceutical and Biomedical Analysis, vol. 15, no. 12, pp. 1867–1876, 1997. View at Publisher · View at Google Scholar · View at Scopus
  195. M.-T. Huang, R. C. Smart, C.-Q. Wong, and A. H. Conney, “Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate,” Cancer Research, vol. 48, no. 21, pp. 5941–5946, 1988. View at Google Scholar · View at Scopus
  196. H. Kikuzaki, M. Hisamoto, K. Hirose, K. Akiyama, and H. Taniguchi, “Antioxidant properties of ferulic acid and its related compounds,” Journal of Agricultural and Food Chemistry, vol. 50, no. 7, pp. 2161–2168, 2002. View at Publisher · View at Google Scholar · View at Scopus
  197. J. Kanski, M. Aksenova, A. Stoyanova, and D. A. Butterfield, “Ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro: structure-activity studies,” The Journal of Nutritional Biochemistry, vol. 13, no. 5, pp. 273–281, 2002. View at Publisher · View at Google Scholar · View at Scopus
  198. H. H. Tønnesen and J. Karlsen, “Studies on curcumin and curcuminoids - VI. Kinetics of curcumin degradation in aqueous solution,” Zeitschrift für Lebensmittel-Untersuchung und -Forschung, vol. 180, no. 5, pp. 402–404, 1985. View at Publisher · View at Google Scholar · View at Scopus
  199. L. Shen and H.-F. Ji, “Contribution of degradation products to the anticancer activity of curcumin,” Clinical Cancer Research, vol. 15, no. 22, p. 7108, 2009. View at Publisher · View at Google Scholar · View at Scopus
  200. Y. Abe, S. Hashimoto, and T. Horie, “Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages,” Pharmacological Research, vol. 39, no. 1, pp. 41–47, 1999. View at Publisher · View at Google Scholar · View at Scopus
  201. A. Paradkar, A. A. Ambike, B. K. Jadhav, and K. R. Mahadik, “Characterization of curcumin-PVP solid dispersion obtained by spray drying,” International Journal of Pharmaceutics, vol. 271, no. 1-2, pp. 281–286, 2004. View at Publisher · View at Google Scholar · View at Scopus
  202. G. B. Elion, A. Kovensky, G. H. Hitchings, E. Metz, and R. W. Rundles, “Metabolic studies of allopurinol, an inhibitor of xanthine oxidase,” Biochemical Pharmacology, vol. 15, no. 7, pp. 863–880, 1966. View at Publisher · View at Google Scholar · View at Scopus
  203. S. Itagaki, T. Kurokawa, C. Nakata et al., “In vitro and in vivo antioxidant properties of ferulic acid: a comparative study with other natural oxidation inhibitors,” Food Chemistry, vol. 114, no. 2, pp. 466–471, 2009. View at Publisher · View at Google Scholar · View at Scopus
  204. W.-S. Chan, P.-C. Wen, and H.-C. Chiang, “Structure-activity relationship of caffeic acid analogues on xanthine oxidase inhibition,” Anticancer Reseach, vol. 15, no. 3, pp. 703–707, 1995. View at Google Scholar · View at Scopus
  205. Y.-C. Chang, F.-W. Lee, C.-S. Chen et al., “Structure-activity relationship of C6-C3 phenylpropanoids on xanthine oxidase-inhibiting and free radical-scavenging activities,” Free Radical Biology & Medicine, vol. 43, no. 11, pp. 1541–1551, 2007. View at Publisher · View at Google Scholar · View at Scopus
  206. F. Borges, E. Fernande, and F. Roleira, “Progress towards the discovery of xanthine oxidase inhibitors,” Current Medicinal Chemistry, vol. 9, no. 2, pp. 195–217, 2002. View at Publisher · View at Google Scholar · View at Scopus
  207. H. Rubbo, R. Radi, and E. Prodanov, “Substrate inhibition of xanthine oxidase and its influence on superoxide radical production,” BBA - General Subjects, vol. 1074, no. 3, pp. 386–391, 1991. View at Publisher · View at Google Scholar · View at Scopus
  208. A. Suzuki, D. Kagawa, A. Fujii, R. Ochiai, I. Tokimitsu, and I. Saito, “Short- and long-term effects of ferulic acid on blood pressure in spontaneously hypertensive rats,” American Journal of Hypertension, vol. 15, no. 4, pp. 351–357, 2002. View at Publisher · View at Google Scholar · View at Scopus
  209. L. Hlavačková, A. Janegová, O. Uličná, P. Janega, A. Černá, and P. Babál, “Spice up the hypertension diet - Curcumin and piperine prevent remodeling of aorta in experimental L-NAME induced hypertension,” Journal of Nutrition and Metabolism, vol. 8, article no. 72, 2011. View at Publisher · View at Google Scholar · View at Scopus
  210. M. Kampa, V.-I. Alexaki, G. Notas et al., “Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action,” Breast Cancer Research, vol. 6, no. 2, pp. R63–R74, 2004. View at Publisher · View at Google Scholar · View at Scopus
  211. F. Yang, B.-R. Zhou, P. Zhang, Y.-F. Zhao, J. Chen, and Y. Liang, “Binding of ferulic acid to cytochrome c enhances stability of the protein at physiological pH and inhibits cytochrome c-induced apoptosis,” Chemico-Biological Interactions, vol. 170, no. 3, pp. 231–243, 2007. View at Publisher · View at Google Scholar · View at Scopus
  212. V. P. Menon and A. R. Sudheer, “Antioxidant and anti-inflammatory properties of curcumin,” in The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease, pp. 105–125, Springer, 2007. View at Google Scholar
  213. T.-Y. Huang, C.-W. Hsu, W.-C. Chang, M.-Y. Wang, J.-F. Wu, and Y.-C. Hsu, “Demethoxycurcumin retards cell growth and induces apoptosis in human brain malignant glioma GBM 8401 cells,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 396573, 11 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  214. A. A. Reinke and J. E. Gestwicki, “Structure-activity relationships of amyloid beta-aggregation inhibitors based on curcumin: Influence of linker length and flexibility,” Chemical Biology & Drug Design, vol. 70, no. 3, pp. 206–215, 2007. View at Publisher · View at Google Scholar · View at Scopus
  215. S.-Y. Park, H.-S. Kim, E.-K. Cho et al., “Curcumin protected PC12 cells against beta-amyloid-induced toxicity through the inhibition of oxidative damage and tau hyperphosphorylation,” Food and Chemical Toxicology, vol. 46, no. 8, pp. 2881–2887, 2008. View at Publisher · View at Google Scholar · View at Scopus
  216. F. Yang, G. P. Lim, A. N. Begum et al., “Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo,” The Journal of Biological Chemistry, vol. 280, no. 7, pp. 5892–5901, 2005. View at Publisher · View at Google Scholar · View at Scopus
  217. T. Hamaguchi, K. Ono, A. Murase, and M. Yamada, “Phenolic compounds prevent Alzheimer's pathology through different effects on the amyloid-beta aggregation pathway,” The American Journal of Pathology, vol. 175, no. 6, pp. 2557–2565, 2009. View at Publisher · View at Google Scholar · View at Scopus
  218. R. Sultana, A. Ravagna, H. Mohmmad-Abdul, V. Calabrese, and D. A. Butterfield, “Ferulic acid ethyl ester protects neurons against amyloid β-peptide(1–42)-induced oxidative stress and neurotoxicity: relationship to antioxidant activity,” Journal of Neurochemistry, vol. 92, no. 4, pp. 749–758, 2005. View at Publisher · View at Google Scholar · View at Scopus
  219. K. Ono, M. Hirohata, and M. Yamada, “Ferulic acid destabilizes preformed β-amyloid fibrils in vitro,” Biochemical and Biophysical Research Communications, vol. 336, no. 2, pp. 444–449, 2005. View at Publisher · View at Google Scholar · View at Scopus
  220. M.-C. Kim, S.-J. Kim, D.-S. Kim et al., “Vanillic acid inhibits inflammatory mediators by suppressing NF-κB in lipopolysaccharide-stimulated mouse peritoneal macrophages,” Immunopharmacology and Immunotoxicology, vol. 33, no. 3, pp. 525–532, 2011. View at Publisher · View at Google Scholar · View at Scopus
  221. H. J. Kim, I. K. Hwang, and M. H. Won, “Vanillin, 4-hydroxybenzyl aldehyde and 4-hydroxybenzyl alcohol prevent hippocampal CA1 cell death following global ischemia,” Brain Research, vol. 1181, no. 1, pp. 130–141, 2007. View at Publisher · View at Google Scholar · View at Scopus
  222. P. Anand, A. B. Kunnumakkara, R. A. Newman, and B. B. Aggarwal, “Bioavailability of curcumin: problems and promises,” Molecular Pharmaceutics, vol. 4, no. 6, pp. 807–818, 2007. View at Publisher · View at Google Scholar · View at Scopus
  223. C. R. Ireson, D. J. Jones, S. Orr et al., “Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine,” Cancer Epidemiology, Biomarkers & Prevention, vol. 11, no. 1, pp. 105–111, 2002. View at Google Scholar
  224. B. B. Aggarwal and B. Sung, “Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets,” Trends in Pharmacological Sciences, vol. 30, no. 2, pp. 85–94, 2009. View at Publisher · View at Google Scholar · View at Scopus
  225. F. Zsila, Z. Bikádi, and M. Simonyi, “Unique, pH-dependent biphasic band shape of the visible circular dichroism of curcumin-serum albumin complex,” Biochemical and Biophysical Research Communications, vol. 301, no. 3, pp. 776–782, 2003. View at Publisher · View at Google Scholar · View at Scopus
  226. S. I. Hoehle, E. Pfeiffer, A. M. Sólyom, and M. Metzler, “Metabolism of curcuminoids in tissue slices and subcellular fractions from rat liver,” Journal of Agricultural and Food Chemistry, vol. 54, no. 3, pp. 756–764, 2006. View at Publisher · View at Google Scholar · View at Scopus
  227. M.-H. Pan, T.-M. Huang, and J.-K. Lin, “Biotransformation of curcumin through reduction and glucuronidation in mice,” Drug Metabolism and Disposition, vol. 27, no. 4, pp. 486–494, 1999. View at Google Scholar · View at Scopus
  228. T. M. A. Elattar and A. S. Virji, “The inhibitory effect of curcumin, genistein, quercetin and cisplatin on the growth of oral cancer cells in vitro,” Anticancer Reseach, vol. 20, no. 3 A, pp. 1733–1738, 2000. View at Google Scholar · View at Scopus
  229. M.-T. Huang, T. Lysz, T. Ferraro, T. F. Abidi, J. D. Laskin, and A. H. Conney, “Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis,” Cancer Research, vol. 51, no. 3, pp. 813–819, 1991. View at Google Scholar · View at Scopus
  230. K. Ono, K. Hasegawa, H. Naiki, and M. Yamada, “Curcumin has potent anti-amyloidogenic effects for Alzheimer's β-amyloid fibrils in vitro,” Journal of Neuroscience Research, vol. 75, no. 6, pp. 742–750, 2004. View at Publisher · View at Google Scholar · View at Scopus
  231. J. L. Arbiser, N. Klauber, . Rohan et al., “Curcumin is an in vivo inhibitor of angiogenesis,” Molecular Medicine, vol. 4, no. 6, p. 376, 1998. View at Google Scholar
  232. M. M. Chan, H. Huang, M. R. Fenton, and D. Fong, “In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties,” Biochemical Pharmacology, vol. 55, no. 12, pp. 1955–1962, 1998. View at Publisher · View at Google Scholar · View at Scopus
  233. C. Ireson, S. Orr, D. J. L. Jones et al., “Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2production,” Cancer Research, vol. 61, no. 3, pp. 1058–1064, 2001. View at Google Scholar · View at Scopus
  234. L. Baum, C. W. K. Lam, S. K. Cheung et al., “Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease,” Journal of Clinical Psychopharmacology, vol. 28, no. 1, pp. 110–113, 2008. View at Publisher · View at Google Scholar · View at Scopus
  235. Y. Tsai, W. Jan, C. Chien, W. Lee, L. Lin, and T. Tsai, “Optimised nano-formulation on the bioavailability of hydrophobic polyphenol, curcumin, in freely-moving rats,” Food Chemistry, vol. 127, no. 3, pp. 918–925, 2011. View at Publisher · View at Google Scholar · View at Scopus
  236. L. P. Volak, S. Ghirmai, J. R. Cashman, and M. H. Court, “Curcuminoids inhibit multiple human cytochromes P450, UDP- glucuronosyltransferase, and sulfotransferase enzymes, whereas piperine is a relatively selective CYP3A4 inhibitor,” Drug Metabolism and Disposition, vol. 36, no. 8, pp. 1594–1605, 2008. View at Publisher · View at Google Scholar · View at Scopus
  237. A.-L. Cheng, C. H. Hsu, J. K. Lin et al., “Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions,” Anticancer Research, vol. 21, no. 48, pp. 2895–2900, 2000. View at Google Scholar
  238. G. M. Holder, J. L. Plummer, and A. J. Ryan, “The metabolism and excretion of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in the rat,” Xenobiotica, vol. 8, no. 12, pp. 761–768, 1978. View at Publisher · View at Google Scholar · View at Scopus
  239. S. Shukla, G. T. MacLennan, P. Fu et al., “Nuclear factor-κB/p65 (Rel A) is constitutively activated in human prostate adenocarcinoma and correlates with disease progression,” Neoplasia, vol. 6, no. 4, pp. 390–400, 2004. View at Publisher · View at Google Scholar · View at Scopus
  240. E. Ardite, J. Panés, M. Miranda et al., “Effects of steroid treatment on activation of nuclear factor κB in patients with inflammatory bowel disease,” British Journal of Pharmacology, vol. 124, no. 3, pp. 431–433, 1998. View at Publisher · View at Google Scholar · View at Scopus
  241. A. Garg and B. B. Aggarwal, “Nuclear transcription factor-κB as a target for cancer drug development,” Leukemia, vol. 16, no. 6, pp. 1053–1068, 2002. View at Publisher · View at Google Scholar · View at Scopus
  242. F. R. Greten and M. Karin, “The IKK/NF-κB activation pathway - A target for prevention and treatment of cancer,” Cancer Letters, vol. 206, no. 2, pp. 193–199, 2004. View at Publisher · View at Google Scholar · View at Scopus
  243. F. H. Sarkar and Y. Li, “NF-kappaB: A potential target for cancer chemoprevention and therapy,” Frontiers in Bioscience, vol. 13, no. 8, pp. 2950–2959, 2008. View at Publisher · View at Google Scholar · View at Scopus
  244. J. Yan and J. M. Greer, “NF-κB, a potential therapeutic target for the treatment of multiple sclerosis,” CNS and Neurological Disorders - Drug Targets, vol. 7, no. 6, pp. 536–557, 2008. View at Publisher · View at Google Scholar · View at Scopus
  245. J. A. Roman-Blas and S. A. Jimenez, “NF-κB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis,” Osteoarthritis and Cartilage, vol. 14, no. 9, pp. 839–848, 2006. View at Publisher · View at Google Scholar · View at Scopus
  246. M. Feldmann, E. Andreakos, C. Smith et al., “Is NF-κB a useful therapeutic target in rheumatoid arthritis?” Annals of the Rheumatic Diseases, vol. 61, supplement 2, pp. i13–i18, 2002. View at Google Scholar
  247. K. D. Brown, E. Claudio, and U. Siebenlist, “The roles of the classical and alternative nuclear factor-κB pathways: potential implications for autoimmunity and rheumatoid arthritis,” Arthritis Research & Therapy, vol. 10, no. 4, article 212, 2008. View at Publisher · View at Google Scholar · View at Scopus
  248. F. R. Greten, L. Eckmann, T. F. Greten et al., “IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer,” Cell, vol. 118, no. 3, pp. 285–296, 2004. View at Publisher · View at Google Scholar · View at Scopus
  249. X. Feng, H. Wang, S. Ye et al., “Up-regulation of microRNA-126 may contribute to pathogenesis of ulcerative colitis via regulating NF-kappaB Inhibitor IκBα,” PLoS ONE, vol. 7, no. 12, Article ID e52782, 2012. View at Publisher · View at Google Scholar · View at Scopus
  250. Y. M. Shah, X. Ma, K. Morimura, I. Kim, and F. J. Gonzalez, “Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-κB target gene expression,” American Journal of Physiology-Gastrointestinal and Liver Physiology, vol. 292, no. 4, pp. G1114–G1122, 2007. View at Publisher · View at Google Scholar · View at Scopus
  251. S. Bacher and M. L. Schmitz, “The NF-ΚB pathway as a potential target for autoimmune disease therapy,” Current Pharmaceutical Design, vol. 10, no. 23, pp. 2827–2837, 2004. View at Publisher · View at Google Scholar · View at Scopus
  252. J. W. Christman, L. H. Lancaster, and T. S. Blackwell, “Nuclear factor κ B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy,” Intensive Care Medicine, vol. 24, no. 11, pp. 1131–1138, 1998. View at Publisher · View at Google Scholar · View at Scopus
  253. S. S. Makarov, “NF-κb as a therapeutic target in chronic inflammation: recent advances,” Molecular Medicine Today, vol. 6, no. 11, pp. 441–448, 2000. View at Publisher · View at Google Scholar · View at Scopus
  254. T. Ishrat, M. N. Hoda, M. B. Khan et al., “Amelioration of cognitive deficits and neurodegeneration by curcumin in rat model of sporadic dementia of Alzheimer's type (SDAT),” European Neuropsychopharmacology, vol. 19, no. 9, pp. 636–647, 2009. View at Publisher · View at Google Scholar · View at Scopus
  255. Z. Liu, Y. Yu, X. Li, C. A. Ross, and W. W. Smith, “Curcumin protects against A53T alpha-synuclein-induced toxicity in a PC12 inducible cell model for Parkinsonism,” Pharmacological Research, vol. 63, no. 5, pp. 439–444, 2011. View at Publisher · View at Google Scholar · View at Scopus
  256. G. Scapagnini, C. Colombrita, M. Amadio et al., “Curcumin activates defensive genes and protects neurons against oxidative stress,” Antioxidants & Redox Signaling, vol. 8, no. 3-4, pp. 395–403, 2006. View at Publisher · View at Google Scholar · View at Scopus
  257. Y.-G. Zhu, X. C. Chen, Z. Z. Chen et al., “Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons,” Acta Pharmacologica Sinica, vol. 25, pp. 1606–1612, 2004. View at Google Scholar
  258. Y. Wang and M. A. Beydoun, “The obesity epidemic in the United States—gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis,” Epidemiologic Reviews, vol. 29, no. 1, pp. 6–28, 2007. View at Publisher · View at Google Scholar · View at Scopus
  259. P. T. James, R. Leach, E. Kalamara, and M. Shayeghi, “The Worldwide Obesity Epidemic,” Obesity Research, vol. 9, no. S11, pp. 228S–233S, 2001. View at Publisher · View at Google Scholar
  260. J. C. Seidell, “Obesity, insulin resistance and diabetes—a worldwide epidemic,” British Journal of Nutrition, vol. 83, supplement 1, pp. S5–S8, 2000. View at Google Scholar · View at Scopus
  261. P. Vitaglione, R. Barone Lumaga, R. Ferracane et al., “Curcumin bioavailability from enriched bread: The effect of microencapsulated ingredients,” Journal of Agricultural and Food Chemistry, vol. 60, no. 13, pp. 3357–3366, 2012. View at Publisher · View at Google Scholar · View at Scopus
  262. B. T. Kurien and R. H. Scofield, “Oral administration of heat-solubilized curcumin for potentially increasing curcumin bioavailability in experimental animals,” International Journal of Cancer, vol. 125, no. 8, pp. 1992-1993, 2009. View at Publisher · View at Google Scholar · View at Scopus
  263. J. Shaikh, D. D. Ankola, V. Beniwal, D. Singh, M. N. V. Ravi Kumar, and J. Pharm, “Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer,” European Journal of Pharmaceutical Sciences, vol. 37, pp. 223–230, 2009. View at Publisher · View at Google Scholar
  264. P. A. Subramani and V. R. Narala, “Challenges of curcumin bioavailability: Novel aerosol remedies,” Natural Product Communications (NPC), vol. 8, no. 1, pp. 121–124, 2013. View at Google Scholar · View at Scopus
  265. M. M. Yallapu, M. C. Ebeling, N. Chauhan, M. Jaggi, and S. C. Chauhan, “Interaction of curcumin nanoformulations with human plasma proteins and erythrocytes,” International Journal of Nanomedicine, vol. 6, pp. 2779–2790, 2011. View at Google Scholar · View at Scopus
  266. S. Bisht and A. Maitra, “Systemic delivery of curcumin: 21st century solutions for an ancient conundrum,” Current Drug Discovery Technologies, vol. 6, pp. 192–199, 2009. View at Publisher · View at Google Scholar
  267. C. Chen, T. D. Johnston, H. Jeon et al., “An in vitro study of liposomal curcumin: Stability, toxicity and biological activity in human lymphocytes and Epstein-Barr virus-transformed human B-cells,” International Journal of Pharmaceutics, vol. 366, no. 1-2, pp. 133–139, 2009. View at Publisher · View at Google Scholar · View at Scopus
  268. G. Liang, L. Shao, Y. Wang et al., “Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents,” Bioorganic & Medicinal Chemistry, vol. 17, pp. 2623–2631, 2009. View at Publisher · View at Google Scholar
  269. A. Jacob, R. Wu, M. Zhou, and P. Wang, “Mechanism of the anti-inflammatory effect of curcumin: PPAR-γ activation,” PPAR Research, vol. 2007, Article ID 89369, 5 pages, 2007. View at Publisher · View at Google Scholar · View at Scopus
  270. L. Shen and H. Ji, “The pharmacology of curcumin: is it the degradation products?” Trends in Molecular Medicine, vol. 18, no. 3, pp. 138–144, 2012. View at Publisher · View at Google Scholar · View at Scopus