The Essential Medicinal Chemistry of Curcumin

Journal of Medicinal Chemistry

Volumn 60, Issue 5, 2017, Pages 1620-1637

  Nelson, Kathryn M ^a   Dahlin, Jayme L ^b   Bisson, Jonathan ^c   Graham, James ^c   Pauli, Guido F ^c   Walters, Michael A ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID; ARTEMISININ; CURCUMIN; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; HISTONE DEACETYLASE 8; NATURAL PRODUCT; TAU PROTEIN;

ALZHEIMER DISEASE; ARTICLE; ATMOSPHERE; BIOLOGICAL ACTIVITY; CLINICAL TRIAL (TOPIC); COLON CANCER; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG METABOLISM; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MEDICINAL CHEMISTRY; MOLECULAR STABILITY; OXIDATION; OXIDATION REDUCTION STATE; PANCREAS CANCER; PHYSICAL CHEMISTRY; RADIATION DERMATITIS; SCIENTIFIC LITERATURE; ANIMAL; CHEMISTRY;

ANIMALS; CHEMISTRY, PHARMACEUTICAL; CURCUMIN; HUMANS;

EID: 85015038999     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b00975     Document Type: Article

References (164)

1. Yuan, D.; Yang, X.; Guo, J. C. A great honor and a huge challenge for China: You-you tu getting the nobel prize in physiology or medicine J. Zhejiang Univ., Sci., B 2016, 17, 405-408 10.1631/jzus.B1600094
2. Hanson, M. Is the 2015 Nobel Prize a turning point for traditional Chinese medicine? https://theconversation.com/is-the-2015-nobel-prize-a-turning-point-for-traditional-chinese-medicine-48643 (accessed June 6, 2016).
3. Baell, J.; Walters, M. A. Chemistry: Chemical con artists foil drug discovery Nature (London, U. K.) 2014, 513, 481-483 10.1038/513481a
4. Bisson, J.; McAlpine, J. B.; Friesen, J. B.; Chen, S.-N.; Graham, J.; Pauli, G. F. Can invalid bioactives undermine natural product-based drug discovery? J. Med. Chem. 2016, 59, 1671-1690 10.1021/acs.jmedchem.5b01009
5. Burgos-Moron, E.; Calderon-Montano, J. M.; Salvador, J.; Robles, A.; Lopez-Lazaro, M. The dark side of curcumin Int. J. Cancer 2010, 126, 1771-1775 10.1002/ijc.24967
6. Baell, J. B. Feeling nature’s PAINS: Natural products, natural product drugs, and pan assay interference compounds (PAINS) J. Nat. Prod. 2016, 79, 616-628 10.1021/acs.jnatprod.5b00947
7. Chin, D.; Huebbe, P.; Pallauf, K.; Rimbach, G. Neuroprotective properties of curcumin in Alzheimer’s disease-merits and limitations Curr. Med. Chem. 2013, 20, 3955-3985 10.2174/09298673113209990210
8. Glaser, J.; Holzgrabe, U. Focus on PAINS: False friends in the quest for selective anti-protozoal lead structures from nature? MedChemComm 2016, 7, 214-223 10.1039/C5MD00481K
9. Heger, M.; van Golen, R. F.; Broekgaarden, M.; Michel, M. C. The molecular basis for the pharmacokinetics and pharmacodynamics of curcumin and its metabolites in relation to cancers Pharmacol. Rev. 2014, 66, 222-307 10.1124/pr.110.004044
10. Elias, G.; Jacob, P. J.; Hareeshbabu, E.; Mathew, V. B.; Krishnan, B.; Krishnakumar, K. Curcumin: Transforming the spice to a wonder drug Int. J. Pharm. Sci. Res. 2015, 6, 2671-2680 10.13040/IJPSR.0975-8232.6(7).2671-80
11. Neckers, L.; Trepel, J.; Lee, S.; Chung, E.-J.; Lee, M.-J.; Jung, Y.-J.; Marcu, M. G. Curcumin is an inhibitor of p300 histone acetyltransferase Med. Chem. (Sharjah, United Arab Emirates) 2006, 2, 169-174 10.2174/157340606776056133
12. Rainey-Smith, S. R.; Brown, B. M.; Sohrabi, H. R.; Shah, T.; Goozee, K. G.; Gupta, V. B.; Martins, R. N. Curcumin and cognition: A randomised, placebo-controlled, double-blind study of community-dwelling older adults Br. J. Nutr. 2016, 115, 2106-2113 10.1017/S0007114516001203
13. Okamura, T.; Kubo, K. Turmeric pigment-containing chocolate with excellent flavor, texture, and hangover prevention/treatment properties. JP2009183206A, 2009.
14. Kwon, H. N. Functional noodles for relieving hangover and its manufacturing method. KR1314917B1, 2013.
15. Rezq, E.-S. A. M.; Mansour, M. T. A.-A.; Kumosani, T. A. Long acting conserved natural functional groups curcumin. WO2010057503A2, 2010.
16. Wang, A.; An, X.; Zhou, Y. Application of curcumin to medicinal preparations for treating erectile dysfunction. CN101822656A, 2010.
17. Isaacs, E.; Cobbledick, T. Complete supplement formulae for maintenance of hair growth and condition. GB2484812A, 2012.
18. Huh, S.; Lee, J.; Jung, E.; Kim, S.-C.; Kang, J.-I.; Lee, J.; Kim, Y.-W.; Sung, Y. K.; Kang, H.-K.; Park, D. A cell-based system for screening hair growth-promoting agents Arch. Dermatol. Res. 2009, 301, 381-385 10.1007/s00403-009-0931-0
19. Ahluwalia, G. S.; Shander, D.; Styczynski, P. Inhibition of hair growth with protein kinase C inhibitors. WO9609806A2, 1996.
20. Jana, S.; Paul, S.; Swarnakar, S. Curcumin as anti-endometriotic agent: Implication of MMP-3 and intrinsic apoptotic pathway Biochem. Pharmacol. (Amsterdam, Neth.) 2012, 83, 797-804 10.1016/j.bcp.2011.12.030
21. Naz, R. K.; Lough, M. L. Curcumin as a potential non-steroidal contraceptive with spermicidal and microbicidal properties Eur. J. Obstet. Gynecol. Reprod. Biol. 2014, 176, 142-148 10.1016/j.ejogrb.2014.01.024
22. Data pertaining to these claims are easily accessible by any Internet search engine, e.g., https://www.google.com/#q=curcumin+AND+health+benefits
23. Goel, A.; Kunnumakkara, A. B.; Aggarwal, B. B. Curcumin as "curecumin": From kitchen to clinic Biochem. Pharmacol. (Amsterdam, Neth.) 2008, 75, 787-809 10.1016/j.bcp.2007.08.016
24. Kumar, A.; Chetia, H.; Sharma, S.; Kabiraj, D.; Talukdar, N. C.; Bora, U. Curcumin resource database Database 2015, 2015, bav070 10.1093/database/bav070
25. Wang, J.; Zhang, C.-J.; Chia, W. N.; Loh, C. C. Y.; Li, Z.; Lee, Y. M.; He, Y.; Yuan, L.-X.; Lim, T. K.; Liu, M.; Liew, C. X.; Lee, Y. Q.; Zhang, J.; Lu, N.; Lim, C. T.; Hua, Z.-C.; Liu, B.; Shen, H.-M.; Tan, K. S. W.; Lin, Q. Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum Nat. Commun. 2015, 6, 10111 10.1038/ncomms10111
26. Medhi, B.; Patyar, S.; Rao, R. S.; Byrav, D. S. P.; Prakash, A. Pharmacokinetic and toxicological profile of artemisinin compounds: An update Pharmacology 2009, 84, 323-332 10.1159/000252658
27. Wang, Y.-J.; Pan, M.-H.; Cheng, A.-L.; Lin, L.-I.; Ho, Y.-S.; Hsieh, C.-Y.; Lin, J.-K. Stability of curcumin in buffer solutions and characterization of its degradation products J. Pharm. Biomed. Anal. 1997, 15, 1867-1876 10.1016/S0731-7085(96)02024-9
28. Yang, K. Y.; Lin, L. C.; Tseng, T. Y.; Wang, S. C.; Tsai, T. H. Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 2007, 853, 183-189 10.1016/j.jchromb.2007.03.010
29. Chow, S.-C.; Chiu, S.-T. A note on design and analysis of clinical trials Drug Des.: Open Access 2013, 2, 102 10.4172/2169-0138.1000102
30. National Institutes of Health. NIH RePORTER. Research portfolio online reporting tools. Reports, data, and analysis of NIH research activities. http://projectreporter.nih.gov/reporter.cfm (accessed October 6, 2016).
31. Kuttan, R.; Bhanumathy, P.; Nirmala, K.; George, M. C. Potential anticancer activity of turmeric (Curcuma longa) Cancer Lett. (N. Y., NY, U. S.) 1985, 29, 197-202 10.1016/0304-3835(85)90159-4
32. Niranjan, A.; Singh, S.; Dhiman, M.; Tewari, S. K. Biochemical composition of Curcuma longa l. Accessions Anal. Lett. 2013, 46, 1069-1083 10.1080/00032719.2012.751541
33. Priyadarsini, K. I. The chemistry of curcumin: From extraction to therapeutic agent Molecules 2014, 19, 20091-20112 10.3390/molecules191220091
34. Food and Drug Administration Office of Food Additive Safety. Agency Response Letter GRAS Notice No. Grn 000460. U.S. Food and Drug Administration, 2013.
35. Majeed, S. The state of the curcumin market. Natural Products Insider; Informa Exhibitions, 2015; http://www.naturalproductsinsider.com/articles/2015/12/the-state-of-the-curcumin-market.aspx.
36. Niranjan, A.; Prakash, D. Chemical constituents and biological activities of turmeric (Curcuma longa l.)-a review J. Food Sci. Technol. (New Delhi, India) 2008, 45, 109-116
37. Panahi, Y.; Hosseini, M. S.; Khalili, N.; Naimi, E.; Majeed, M.; Sahebkar, A. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis Clin. Nutr. 2015, 34, 1101-1108 10.1016/j.clnu.2014.12.019
38. Yue, G. G.; Chan, B. C.; Hon, P. M.; Lee, M. Y.; Fung, K. P.; Leung, P. C.; Lau, C. B. Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa Food Chem. Toxicol. 2010, 48, 2011-2020 10.1016/j.fct.2010.04.039
39. Hu, S.; Maiti, P.; Ma, Q.; Zuo, X.; Jones, M. R.; Cole, G. M.; Frautschy, S. A. Clinical development of curcumin in neurodegenerative disease Expert Rev. Neurother. 2015, 15, 629-637 10.1586/14737175.2015.1044981
40. Baell, J. B.; Holloway, G. A. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays J. Med. Chem. 2010, 53, 2719-2740 10.1021/jm901137j
41. Fang, J.; Lu, J.; Holmgren, A. Thioredoxin reductase is irreversibly modified by curcumin: A novel molecular mechanism for its anticancer activity J. Biol. Chem. 2005, 280, 25284-25290 10.1074/jbc.M414645200
42. Jurrmann, N.; Birgelius-Flohe, R.; Boel, G.-F. Curcumin blocks interleukin-1 (IL-1) signaling by inhibiting the recruitment of the IL-1 receptor-associated kinase IRAK in murine thymoma EL-4 cells J. Nutr. 2005, 135, 1859-1864
43. Jung, Y.; Xu, W.; Kim, H.; Ha, N.; Neckers, L. Curcumin-induced degradation of ErbB2: A role for the E3 ubiquitin ligase CHIP and the Michael reaction acceptor activity of curcumin Biochim. Biophys. Acta, Mol. Cell Res. 2007, 1773, 383-390 10.1016/j.bbamcr.2006.11.004
44. Chin, D.; Huebbe, P.; Frank, J.; Rimbach, G.; Pallauf, K. Curcumin may impair iron status when fed to mice for six months Redox Biol. 2014, 2, 563-569 10.1016/j.redox.2014.01.018
45. Schneider, C.; Gordon, O. N.; Edwards, R. L.; Luis, P. B. Degradation of curcumin: From mechanism to biological implications J. Agric. Food Chem. 2015, 63, 7606-7614 10.1021/acs.jafc.5b00244
46. Duan, D.; Doak, A. K.; Nedyalkova, L.; Shoichet, B. K. Colloidal aggregation and the in vitro activity of traditional Chinese medicines ACS Chem. Biol. 2015, 10, 978-988 10.1021/cb5009487
47. Ingolfsson, H. I.; Thakur, P.; Herold, K. F.; Hobart, E. A.; Ramsey, N. B.; Periole, X.; de Jong, D. H.; Zwama, M.; Yilmaz, D.; Hall, K.; Maretzky, T.; Hemmings, H. C., Jr.; Blobel, C.; Marrink, S. J.; Kocer, A.; Sack, J. T.; Andersen, O. S. Phytochemicals perturb membranes and promiscuously alter protein function ACS Chem. Biol. 2014, 9, 1788-1798 10.1021/cb500086e
48. Priyadarsini, K. I. Photophysics, photochemistry and photobiology of curcumin: Studies from organic solutions, bio-mimetics and living cells J. Photochem. Photobiol., C 2009, 10, 81-95 10.1016/j.jphotochemrev.2009.05.001
49. Esatbeyoglu, T.; Ulbrich, K.; Rehberg, C.; Rohn, S.; Rimbach, G. Thermal stability, antioxidant, and anti-inflammatory activity of curcumin and its degradation product 4-vinyl guaiacol Food Funct. 2015, 6, 887-893 10.1039/C4FO00790E
50. Avonto, C.; Taglialatela-Scafati, O.; Pollastro, F.; Minassi, A.; Di Marzo, V.; De Petrocellis, L.; Appendino, G. An NMR spectroscopic method to identify and classify thiol-trapping agents: Revival of Michael acceptors for drug discovery? Angew. Chem., Int. Ed. 2011, 50, 467-471 10.1002/anie.201005959
51. Pauli, G. F.; Chen, S. N.; Friesen, J. B.; McAlpine, J. B.; Jaki, B. U. Analysis and purification of bioactive natural products: The AnaPurNa study J. Nat. Prod. 2012, 75, 1243-1255 10.1021/np300066q
52. Simmler, C.; Hajirahimkhan, A.; Lankin, D. C.; Bolton, J. L.; Jones, T.; Soejarto, D. D.; Chen, S. N.; Pauli, G. F. Dynamic residual complexity of the isoliquiritigenin-liquiritigenin interconversion during bioassay J. Agric. Food Chem. 2013, 61, 2146-2157 10.1021/jf304445p
53. Gordon, O. N.; Luis, P. B.; Sintim, H. O.; Schneider, C. Unraveling curcumin degradation: Autoxidation proceeds through spiroepoxide and vinylether intermediates en route to the main bicyclopentadione J. Biol. Chem. 2015, 290, 4817-4828 10.1074/jbc.M114.618785
54. Workman, P.; Collins, I. Probing the probes: Fitness factors for small molecule tools Chem. Biol. (Oxford, U. K.) 2010, 17, 561-577 10.1016/j.chembiol.2010.05.013
55. Singh, J.; Petter, R. C.; Baillie, T. A.; Whitty, A. The resurgence of covalent drugs Nat. Rev. Drug Discovery 2011, 10, 307-317 10.1038/nrd3410
56. Kalgutkar, A. S.; Dalvie, D. K. Drug discovery for a new generation of covalent drugs Expert Opin. Drug Discovery 2012, 7, 561-581 10.1517/17460441.2012.688744
57. Schröder, J.; Klinger, A.; Oellien, F.; Marhoefer, R. J.; Duszenko, M.; Selzer, P. M. Docking-based virtual screening of covalently binding ligands: An orthogonal lead discovery approach J. Med. Chem. 2013, 56, 1478-1490 10.1021/jm3013932
58. Davids, M. S.; Brown, J. R. Ibrutinib: A first in class covalent inhibitor of Bruton’s tyrosine kinase Future Oncol. 2014, 10, 957-967 10.2217/fon.14.51
59. Flanagan, M. E.; Abramite, J. A.; Anderson, D. P.; Aulabaugh, A.; Dahal, U. P.; Gilbert, A. M.; Li, C.; Montgomery, J.; Oppenheimer, S. R.; Ryder, T.; Schuff, B. P.; Uccello, D. P.; Walker, G. S.; Wu, Y.; Brown, M. F.; Chen, J. M.; Hayward, M. M.; Noe, M. C.; Obach, R. S.; Philippe, L.; Shanmugasundaram, V.; Shapiro, M. J.; Starr, J.; Stroh, J.; Che, Y. Chemical and computational methods for the characterization of covalent reactive groups for the prospective design of irreversible inhibitors J. Med. Chem. 2014, 57, 10072-10079 10.1021/jm501412a
60. Jost, C.; Nitsche, C.; Scholz, T.; Roux, L.; Klein, C. D. Promiscuity and selectivity in covalent enzyme inhibition: A systematic study of electrophilic fragments J. Med. Chem. 2014, 57, 7590-7599 10.1021/jm5006918
61. Mah, R.; Thomas, J. R.; Shafer, C. M. Drug discovery considerations in the development of covalent inhibitors Bioorg. Med. Chem. Lett. 2014, 24, 33-39 10.1016/j.bmcl.2013.10.003
62. Moghaddam, M. F.; Tang, Y.; O’Brien, Z.; Richardson, S. J.; Bacolod, M.; Chaturedi, P.; Apuy, J.; Kulkarni, A. A proposed screening paradigm for discovery of covalent inhibitor drugs Drug Metab. Lett. 2014, 8, 19-30 10.2174/1872312808666140317151735
63. Payton, F.; Sandusky, P.; Alworth, W. L. NMR study of the solution structure of curcumin J. Nat. Prod. 2007, 70, 143-146 10.1021/np060263s
64. Jagannathan, R.; Abraham, P. M.; Poddar, P. Temperature-dependent spectroscopic evidences of curcumin in aqueous medium: A mechanistic study of its solubility and stability J. Phys. Chem. B 2012, 116, 14533-14540 10.1021/jp3050516
65. Takagi, T.; Ramachandran, C.; Bermejo, M.; Yamashita, S.; Yu, L. X.; Amidon, G. L. A provisional biopharmaceutical classification of the top 200 oral drug products in the United States, Great Britain, Spain, and Japan Mol. Pharmaceutics 2006, 3, 631-643 10.1021/mp0600182
66. Griesser, M.; Pistis, V.; Suzuki, T.; Tejera, N.; Pratt, D. A.; Schneider, C. Autoxidative and cyclooxygenase-2 catalyzed transformation of the dietary chemopreventive agent curcumin J. Biol. Chem. 2011, 286, 1114-1124 10.1074/jbc.M110.178806
67. Gordon, O. N.; Schneider, C. Vanillin and ferulic acid: Not the major degradation products of curcumin Trends Mol. Med. 2012, 18, 361-363 (author reply, pp 363-364) 10.1016/j.molmed.2012.04.011
68. Khurana, A.; Ho, C. T. High-performance liquid-chromatographic analysis of curcuminoids and their photo-oxidative decomposition compounds in Curcuma longa l J. Liq. Chromatogr. 1988, 11, 2295-2304 10.1080/01483918808067200
69. Tønnesen, H. H.; Karlsen, J.; van Henegouwen, G. B. Studies on curcumin and curcuminoids. VIII. Photochemical stability of curcumin Z. Lebensm.-Unters. Forsch. 1986, 183, 116-122 10.1007/BF01041928
70. Ghosh, M.; Singh, A. T.; Xu, W.; Sulchek, T.; Gordon, L. I.; Ryan, R. O. Curcumin nanodisks: Formulation and characterization Nanomedicine 2011, 7, 162-167 10.1016/j.nano.2010.08.002
71. Sun, M.; Su, X.; Ding, B.; He, X.; Liu, X.; Yu, A.; Lou, H.; Zhai, G. Advances in nantoechnology-based delivery systems for curcumin Nanomedicine (London, U. K.) 2012, 7, 1085-1100 10.2217/nnm.12.80
72. Tamvakopoulos, C.; Dimas, K.; Sofianos, Z. D.; Hatziantoniou, S.; Han, Z.; Liu, Z. L.; Wyche, J. H.; Pantazis, P. Metabolism and anticancer activity of the curcumin analogue, dimethoxycurcumin Clin. Cancer Res. 2007, 13, 1269-1277 10.1158/1078-0432.CCR-06-1839
73. Robinson, T. P.; Hubbard, R. B. t.; Ehlers, T. J.; Arbiser, J. L.; Goldsmith, D. J.; Bowen, J. P. Synthesis and biological evaluation of aromatic enones related to curcumin Bioorg. Med. Chem. 2005, 13, 4007-4013 10.1016/j.bmc.2005.03.054
74. Liang, G.; Shao, L.; Wang, Y.; Zhao, C.; Chu, Y.; Xiao, J.; Zhao, Y.; Li, X.; Yang, S. Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents Bioorg. Med. Chem. 2009, 17, 2623-2631 10.1016/j.bmc.2008.10.044
75. Lim, T.-G.; Lee, S.-Y.; Huang, Z.; Lim, D. Y.; Chen, H.; Jung, S. K.; Bode, A. M.; Lee, K. W.; Dong, Z. Curcumin suppresses proliferation of colon cancer cells by targeting CDK2 Cancer Prev. Res. 2014, 7, 466-474 10.1158/1940-6207.CAPR-13-0387
76. Balasubramanian, K. Molecular orbital basis for yellow curry spice curcumin’s prevention of Alzheimer’s disease J. Agric. Food Chem. 2006, 54, 3512-3520 10.1021/jf0603533
77. Ciccone, L.; Tepshi, L.; Nencetti, S.; Stura, E. A. Transthyretin complexes with curcumin and bromo-estradiol: Evaluation of solubilizing multicomponent mixtures New Biotechnol. 2015, 32, 54-64 10.1016/j.nbt.2014.09.002
78. Irwin, J. J.; Duan, D.; Torosyan, H.; Doak, A. K.; Ziebart, K. T.; Sterling, T.; Tumanian, G.; Shoichet, B. K. An aggregation advisor for ligand discovery J. Med. Chem. 2015, 58, 7076-7087 10.1021/acs.jmedchem.5b01105
79. Coan, K. E.; Shoichet, B. K. Stoichiometry and physical chemistry of promiscuous aggregate-based inhibitors J. Am. Chem. Soc. 2008, 130, 9606-9612 10.1021/ja802977h
80. Coan, K. E. D.; Maltby, D. A.; Burlingame, A. L.; Shoichet, B. K. Promiscuous aggregate-based inhibitors promote enzyme unfolding J. Med. Chem. 2009, 52, 2067-2075 10.1021/jm801605r
81. Winter, S.; Tortik, N.; Kubin, A.; Krammer, B.; Plaetzer, K. Back to the roots: Photodynamic inactivation of bacteria based on water-soluble curcumin bound to polyvinylpyrrolidone as a photosensitizer Photochem. Photobiol. Sci. 2013, 12, 1795-1802 10.1039/c3pp50095k
82. Siviero, A.; Gallo, E.; Maggini, V.; Gori, L.; Mugelli, A.; Firenzuoli, F.; Vannacci, A. Curcumin, a golden spice with a low bioavailability Journal of Herbal Medicine 2015, 5, 57-70 10.1016/j.hermed.2015.03.001
83. Lao, C. D.; Ruffin, M. T. I. V.; Normolle, D.; Heath, D. D.; Murray, S. I.; Bailey, J. M.; Boggs, M. E.; Crowell, J.; Rock, C. L.; Brenner, D. E. Dose escalation of a curcuminoid formulation BMC Complementary Altern. Med. 2006, 6, 10 10.1186/1472-6882-6-10
84. Wahlang, B.; Pawar, Y. B.; Bansal, A. K. Identification of permeability-related hurdles in oral delivery of curcumin using the Caco-2 cell model Eur. J. Pharm. Biopharm. 2011, 77, 275-282 10.1016/j.ejpb.2010.12.006
85. Volpe, D. A.; Faustino, P. J.; Ciavarella, A. B.; Asafu-Adjaye, E. B.; Ellison, C. D.; Yu, L. X.; Hussain, A. S. Classification of drug permeability with a Caco-2 cell monolayer assay Clin. Res. Regul. Aff. 2007, 24, 39-47 10.1080/10601330701273669
86. Suresh, D.; Srinivasan, K. Tissue distribution & elimination of capsaicin, piperine & curcumin following oral intake in rats Indian J. Med. Res. 2010, 131, 682-691
87. Ravindranath, V.; Chandrasekhara, N. Absorption and tissue distribution of curcumin in rats Toxicology 1980, 16, 259-265 10.1016/0300-483X(80)90122-5
88. Ravindranath, V.; Chandrasekhara, N. Metabolism of curcumin-studies with [3H]curcumin Toxicology 1982, 22, 337-344 10.1016/0300-483X(81)90027-5
89. Mathews, S.; Rao, M. N. A. Interaction of curcumin with glutathione Int. J. Pharm. (Amsterdam, Neth.) 1991, 76, 257-259 10.1016/0378-5173(91)90278-V
90. Asai, A.; Miyazawa, T. Occurrence of orally administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma Life Sci. 2000, 67, 2785-2793 10.1016/S0024-3205(00)00868-7
91. Sharma, R. A.; McLelland, H. R.; Hill, K. A.; Ireson, C. R.; Euden, S. A.; Manson, M. M.; Pirmohamed, M.; Marnett, L. J.; Gescher, A. J.; Steward, W. P. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer Clin. Cancer Res. 2001, 7, 1894-1900
92. Garcea, G.; Berry, D. P.; Jones, D. J. L.; Singh, R.; Dennison, A. R.; Farmer, P. B.; Sharma, R. A.; Steward, W. P.; Gescher, A. J. Consumption of the putative chemopreventative agent curcumin by cancer patients: Assessment of curcumin levels in the colorectum and their pharmacodynamic consequences Cancer Epidemiol., Biomarkers Prev. 2005, 14, 120-125
93. Johnson, J. J.; Mukhtar, H. Curcumin for chemoprevention of colon cancer Cancer Lett. (N. Y., NY, U. S.) 2007, 255, 170-181 10.1016/j.canlet.2007.03.005
94. Vareed, S. K.; Kakarala, M.; Ruffin, M. T.; Crowell, J. A.; Normolle, D. P.; Djuric, Z.; Brenner, D. E. Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects Cancer Epidemiol., Biomarkers Prev. 2008, 17, 1411-1417 10.1158/1055-9965.EPI-07-2693
95. Chan, E.; Tan, M.; Xin, J.; Sudarsanam, S.; Johnson, D. E. Interactions between traditional Chinese medicines and western therapeutics Curr. Opin. Drug Discovery Dev. 2010, 13, 50-65
96. Hong, D. H.; Son, Y. K.; Choi, I.-W.; Park, W. S. The inhibitory effect of curcumin on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells Biochem. Biophys. Res. Commun. 2013, 430, 307-312 10.1016/j.bbrc.2012.10.132
97. Bamba, Y.; Yun, Y. S.; Kunugi, A.; Inoue, H. Compounds isolated from Curcuma aromatica Salisb. inhibit human P450 enzymes J. Nat. Med. 2011, 65, 583-587 10.1007/s11418-011-0507-0
98. Gupta, S. C.; Kismali, G.; Aggarwal, B. B. Curcumin, a component of turmeric: From farm to pharmacy BioFactors 2013, 39, 2-13 10.1002/biof.1079
99. Schramm, A.; Jahne, E. A.; Baburin, I.; Hering, S.; Hamburger, M. Natural products as potential human ether-a-go-go-related gene channel inhibitors-outcomes from a screening of widely used herbal medicines and edible plants Planta Med. 2014, 80, 1045-1050 10.1055/s-0034-1382907
100. Xia, M.; Shahane, S. A.; Huang, R.; Titus, S. A.; Shum, E.; Zhao, Y.; Southall, N.; Zheng, W.; Witt, K. L.; Tice, R. R.; Austin, C. P. Identification of quaternary ammonium compounds as potent inhibitors of hERG potassium channels Toxicol. Appl. Pharmacol. 2011, 252, 250-258 10.1016/j.taap.2011.02.016
101. Hu, C.-W.; Sheng, Y.; Zhang, Q.; Liu, H.-B.; Xie, X.; Ma, W.-C.; Huo, R.; Dong, D.-L. Curcumin inhibits hERG potassium channels in vitro Toxicol. Lett. 2012, 208, 192-196 10.1016/j.toxlet.2011.11.005
102. Zhang, G.; Nitteranon, V.; Chan, L. Y.; Parkin, K. L. Glutathione conjugation attenuates biological activities of 6-dehydroshogaol from ginger Food Chem. 2013, 140, 1-8 10.1016/j.foodchem.2013.02.073
103. McFadden, R.-M. T.; Larmonier, C. B.; Shehab, K. W.; Midura-Kiela, M.; Ramalingam, R.; Harrison, C. A.; Besselsen, D. G.; Chase, J. H.; Caporaso, J. G.; Jobin, C.; Ghishan, F. K.; Kiela, P. R. The role of curcumin in modulating colonic microbiota during colitis and colon cancer prevention Inflamm Bowel Dis. 2015, 21, 2483-2494 10.1097/MIB.0000000000000522
104. Gupta, S. C.; Prasad, S.; Kim, J. H.; Patchva, S.; Webb, L. J.; Priyadarsini, I. K.; Aggarwal, B. B. Multitargeting by curcumin as revealed by molecular interaction studies Nat. Prod. Rep. 2011, 28, 1937-1955 10.1039/c1np00051a
105. Ghosh, S.; Banerjee, S.; Sil, P. C. The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update Food Chem. Toxicol. 2015, 83, 111-124 10.1016/j.fct.2015.05.022
106. Oliveira, A. S.; Sousa, E.; Vasconcelos, M. H.; Pinto, M. Curcumin: A natural lead for potential new drug candidates Curr. Med. Chem. 2015, 22, 4196-4232 10.2174/0929867322666151029104611
107. Kundu, P.; Mohanty, C.; Sahoo, S. K. Antiglioma activity of curcumin-loaded lipid nanoparticles and its enhanced bioavailability in brain tissue for effective glioblastoma therapy Acta Biomater. 2012, 8, 2670-2687 10.1016/j.actbio.2012.03.048
108. Dilnawaz, F.; Singh, A.; Sahoo, S. K. Transferrin-conjugated curcumin-loaded superparamagnetic iron oxide nanoparticles induce augmented cellular uptake and apoptosis in K562 cells Acta Biomater. 2012, 8, 704-719 10.1016/j.actbio.2011.10.022
109. Ni, Z.; Xing, F.; Wang, P.; Cao, G. Retracted: Synthesis, characterization and release of curcumin-intercalated Mg-Al-layered double hydroxides Appl. Clay Sci. 2008, 40, 72-80 10.1016/j.clay.2007.07.008
110. Tomita, M.; Kawakami, H.; Uchihara, J. N.; Okudaira, T.; Masuda, M.; Takasu, N.; Matsuda, T.; Ohta, T.; Tanaka, Y.; Mori, N. Curcumin suppresses constitutive activation of AP-1 by downregulation of Jund protein in HTLV-1-infected T-cell lines Leuk. Res. 2006, 30, 313-321 10.1016/j.leukres.2005.08.004
111. Mishra, A.; Kumar, R.; Tyagi, A.; Kohaar, I.; Hedau, S.; Bharti, A. C.; Sarker, S.; Dey, D.; Saluja, D.; Das, B. Curcumin modulates cellular AP-1, NF-kB, and HPV16 E6 proteins in oral cancer ecancer 2015, 9, 525 10.3332/ecancer.2015.525
112. Tomita, M. et al. Retraction: Curcumin targets Akt cell survival signaling pathway in HTLV-I-infected T-cell lines Cancer Sci. 2011, 102, 499 10.1111/j.1349-7006.2010.01831.x
113. Balasubramanyam, K.; Varier, R. A.; Altaf, M.; Swaminathan, V.; Siddappa, N. B.; Ranga, U.; Kundu, T. K. Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription J. Biol. Chem. 2004, 279, 51163-51171 10.1074/jbc.M409024200
114. Simon, R. P.; Robaa, D.; Alhalabi, Z.; Sippl, W.; Jung, M. Katching-up on small molecule modulators of lysine acetyltransferases J. Med. Chem. 2016, 59, 1249-1270 10.1021/acs.jmedchem.5b01502
115. Lu, X.; Deng, Y.; Yu, D.; Cao, H.; Wang, L.; Liu, L.; Yu, C.; Zhang, Y.; Guo, X.; Yu, G. Histone acetyltransferase p300 mediates histone acetylation of PS1 and BACE1 in a cellular model of Alzheimer’s disease PLoS One 2014, 9, e103067 10.1371/journal.pone.0103067
116. Cui, L.; Miao, J.; Cui, L. Cytotoxic effect of curcumin on malaria parasite Plasmodium falciparum: Inhibition of histone acetylation and generation of reactive oxygen species Antimicrob. Agents Chemother. 2007, 51, 488-494 10.1128/AAC.01238-06
117. Kutluay, S. B.; Doroghazi, J.; Roemer, M. E.; Triezenberg, S. J. Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/CBP histone acetyltransferase activity Virology 2008, 373, 239-247 10.1016/j.virol.2007.11.028
118. Kang, S.-K.; Cha, S.-H.; Jeon, H.-G. Curcumin-induced histone hypoacetylation enhances caspase-3-dependent glioma cell death and neurogenesis of neural progenitor cells Stem Cells Dev. 2006, 15, 165-174 10.1089/scd.2006.15.165
119. Chen, W.; Bacanamwo, M.; Harrison, D. G. Activation of p300 histone acetyltransferase activity is an early endothelial response to laminar shear stress and is essential for stimulation of endothelial nitric-oxide synthase mRNA transcription J. Biol. Chem. 2008, 283, 16293-16298 10.1074/jbc.M801803200
120. Chiu, J.; Khan, Z. A.; Farhangkhoee, H.; Chakrabarti, S. Curcumin prevents diabetes-associated abnormalities in the kidneys by inhibiting p300 and nuclear factor-kappaB Nutrition 2009, 25, 964-972 10.1016/j.nut.2008.12.007
121. Collins, H. M.; Abdelghany, M. K.; Messmer, M.; Yue, B.; Deeves, S. E.; Kindle, K. B.; Mantelingu, K.; Aslam, A.; Winkler, G. S.; Kundu, T. K.; Heery, D. M. Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells BMC Cancer 2013, 13, 37 10.1186/1471-2407-13-37
122. Dahlin, J. L.; Nissink, J. W. M.; Strasser, J. M.; Francis, S.; Higgins, L.; Zhou, H.; Zhang, Z.; Walters, M. A. PAINS in the assay: Chemical mechanisms of assay interference and promiscuous enzymatic inhibition observed during a sulfhydryl-scavenging HTS J. Med. Chem. 2015, 58, 2091-2113 10.1021/jm5019093
123. Bora-Tatar, G.; Dayangac-Erden, D.; Demir, A. S.; Dalkara, S.; Yelekci, K.; Erdem-Yurter, H. Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studies Bioorg. Med. Chem. 2009, 17, 5219-5228 10.1016/j.bmc.2009.05.042
124. Wang, S.-H.; Lin, P.-Y.; Chiu, Y.-C.; Huang, J.-S.; Kuo, Y.-T.; Wu, J.-C.; Chen, C.-C. Curcumin-mediated HDAC inhibition suppresses the DNA damage response and contributes to increased DNA damage sensitivity PLoS One 2015, 10, e0134110/0134111-e0134110/0134119 10.1371/journal.pone.0134110
125. Link, A.; Balaguer, F.; Goel, A. Cancer chemoprevention by dietary polyphenols: Promising role for epigenetics Biochem. Pharmacol. (Amsterdam, Neth.) 2010, 80, 1771-1792 10.1016/j.bcp.2010.06.036
126. Rajendran, P.; Ho, E.; Williams, D. E.; Dashwood, R. H. Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells Clin. Epigenet. 2011, 3, 4 10.1186/1868-7083-3-4
127. Bustanji, Y.; Taha, M. O.; Almasri, I. M.; Al-Ghussein, M. A. S.; Mohammad, M. K.; Alkhatib, H. S. Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation J. Enzyme Inhib. Med. Chem. 2009, 24, 771-778 10.1080/14756360802364377
128. Di Martino, R. M.; De Simone, A.; Andrisano, V.; Bisignano, P.; Bisi, A.; Gobbi, S.; Rampa, A.; Fato, R.; Bergamini, C.; Perez, D. I.; Martinez, A.; Bottegoni, G.; Cavalli, A.; Belluti, F. Versatility of the curcumin scaffold: Discovery of potent and balanced dual BACE-1 and GSK-3beta inhibitors J. Med. Chem. 2016, 59, 531-544 10.1021/acs.jmedchem.5b00894
129. Zhang, X.; Yin, W. K.; Shi, X. D.; Li, Y. Curcumin activates Wnt/beta-catenin signaling pathway through inhibiting the activity of GSK-3beta in APPswe transfected SY5Y cells Eur. J. Pharm. Sci. 2011, 42, 540-546 10.1016/j.ejps.2011.02.009
130. Yun, J. H.; Park, Y. G.; Lee, K. M.; Kim, J.; Nho, C. W. Curcumin induces apoptotic cell death via Oct4 inhibition and GSK-3beta activation in NCCIT cells Mol. Nutr. Food Res. 2015, 59, 1053-1062 10.1002/mnfr.201400739
131. Xiong, Z.; Hongmei, Z.; Lu, S.; Yu, L. Curcumin mediates presenilin-1 activity to reduce β-amyloid production in a model of Alzheimer’s disease Pharmacol. Rep. 2011, 63, 1101-1108 10.1016/S1734-1140(11)70629-6
132. Dahlin, J. L.; Inglese, J.; Walters, M. A. Mitigating risk in academic preclinical drug discovery Nat. Rev. Drug Discovery 2015, 14, 279-294 10.1038/nrd4578
133. Yang, F.; Lim, G. P.; Begum, A. N.; Ubeda, O. J.; Simmons, M. R.; Ambegaokar, S. S.; Chen, P. P.; Kayed, R.; Glabe, C. G.; Frautschy, S. A.; Cole, G. M. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo J. Biol. Chem. 2005, 280, 5892-5901 10.1074/jbc.M404751200
134. Hudson, S. A.; Ecroyd, H.; Kee, T. W.; Carver, J. A. The thioflavin T fluorescence assay for amyloid fibril detection can be biased by the presence of exogenous compounds FEBS J. 2009, 276, 5960-5972 10.1111/j.1742-4658.2009.07307.x
135. Thapa, A.; Jett, S. D.; Chi, E. Y. Curcumin attenuates amyloid-β aggregate toxicity and modulates amyloid-β aggregation pathway ACS Chem. Neurosci. 2016, 7, 56-68 10.1021/acschemneuro.5b00214
136. Kayed, R.; Head, E.; Thompson, J. L.; McIntire, T. M.; Milton, S. C.; Cotman, C. W.; Glabe, C. G. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis Science (Washington, DC, U. S.) 2003, 300, 486-489 10.1126/science.1079469
137. Feng, B. Y.; Shoichet, B. K. A detergent-based assay for the detection of promiscuous inhibitors Nat. Protoc. 2006, 1, 550-553 10.1038/nprot.2006.77
138. Egan, M. E.; Pearson, M.; Weiner, S. A.; Rajendran, V.; Rubin, D.; Gloeckner-Pagel, J.; Canny, S.; Du, K.; Lukacs, G. L.; Caplan, M. J. Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects Science (Washington, DC, U. S.) 2004, 304, 600-602 10.1126/science.1093941
139. Song, Y.; Sonawane, N. D.; Salinas, D.; Qian, L.; Pedemonte, N.; Galietta, L. J. V.; Verkman, A. S. Evidence against the rescue of defective ΔF508-CFTR cellular processing by curcumin in cell culture and mouse models J. Biol. Chem. 2004, 279, 40629-40633 10.1074/jbc.M407308200
140. Dey, I.; Shah, K.; Bradbury, N. A. Natural compounds as therapeutic agents in the treatment cystic fibrosis J. Genet. Syndr. Gene Ther. 2016, 7, 284 10.4172/2157-7412.1000284
141. Seely, K. A.; Levi, M. S.; Prather, P. L. The dietary polyphenols trans-resveratrol and curcumin selectively bind human CB1 cannabinoid receptors with nanomolar affinities and function as antagonists/inverse agonists J. Pharmacol. Exp. Ther. 2009, 330, 31-39 10.1124/jpet.109.151654
142. Prather, P. L.; Seely, K. A.; Levi, M. S. Notice of retraction J. Pharmacol. Exp. Ther. 2009, 331, 1147
143. Sharma, C.; Sadek, B.; Goyal, S. N.; Sinha, S.; Kamal, M. A.; Ojha, S. Small molecules from nature targeting G-protein coupled cannabinoid receptors: Potential leads for drug discovery and development Evidence-Based Complementary Altern. Med. 2015, 2015, 238482 10.1155/2015/238482
144. Code of Federal Regulations Title 21. Part 182: Substances Generally Recognized as Safe. Section 182.20 Essential oils, oleoresins (solvent-free), and natural extractives (including distillates). U.S. Food and Drug Administration, 2016.
145. Ringman, J. M.; Bardens, J.; Apostolova, L. G.; Frautschy, S. A.; Teng, E.; Cole, G. M.; Begum, A. N.; Beigi, M.; Gylys, K. H.; Badmaev, V.; Heath, D. D.; Porter, V.; Vanek, Z.; Marshall, G. A.; Hellemann, G.; Sugar, C.; Masterman, D. L.; Montine, T. J.; Cummings, J. L. Oral curcumin for Alzheimer’s disease: Tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study Alzheimer's Res. Ther. 2012, 4, 43 10.1186/alzrt146
146. Pfizer. Bioequivalence study comparing a new 10 mg atorvastatin tablet to a 10 mg atorvastatin commercial tablet. https://clinicaltrials.gov/ct2/show/NCT00917579, 2009
147. Sharma, R. A.; Euden, S. A.; Platton, S. L.; Cooke, D. N.; Shafayat, A.; Hewitt, H. R.; Marczylo, T. H.; Morgan, B.; Hemingway, D.; Plummer, S. M.; Pirmohamed, M.; Gescher, A. J.; Steward, W. P. Phase I clinical trial of oral curcumin: Biomarkers of systemic activity and compliance Clin. Cancer Res. 2004, 10, 6847-6854 10.1158/1078-0432.CCR-04-0744
148. Dhillon, N.; Aggarwal, B. B.; Newman, R. A.; Wolff, R. A.; Kunnumakkara, A. B.; Abbruzzese, J. L.; Ng, C. S.; Badmaev, V.; Kurzrock, R. Phase II trial of curcumin in patients with advanced pancreatic cancer Clin. Cancer Res. 2008, 14, 4491-4499 10.1158/1078-0432.CCR-08-0024
149. Asher, G. N.; Spelman, K. Clinical utility of curcumin extract Altern. Ther. Health Med. 2013, 19, 20-22
150. Gupta, S. C.; Patchva, S.; Aggarwal, B. B. Therapeutic roles of curcumin: Lessons learned from clinical trials AAPS J. 2013, 15, 195-218 10.1208/s12248-012-9432-8
151. Hsu, C.-H.; Cheng, A.-L. Clinical studies with curcumin Adv. Exp. Med. Biol. 2007, 595, 471-480 10.1007/978-0-387-46401-5_21
152. Oppenheimer, A. Turmeric (curcumin) in biliary diseases Lancet 1937, 229, 619-621 10.1016/S0140-6736(00)98193-5
153. National Institutes of Health. "ClinicalTrials.gov." Registry and results database of clinical studies of human participants. http://clinicaltrials.gov (accessed October 6, 2016).
154. Hurlstone, D. P.; Karajeh, M.; Sanders, D. S.; Drew, S. K.; Cross, S. S. Rectal aberrant crypt foci identified using high-magnification-chromoscopic colonoscopy: Biomarkers for flat and depressed neoplasia Am. J. Gastroenterol. 2005, 100, 1283-1289 10.1111/j.1572-0241.2005.40891.x
155. Mattson, M. P.; Cheng, A. Neurohormetic phytochemicals: Low-dose toxins that induce adaptive neuronal stress responses Trends Neurosci. 2006, 29, 632-639 10.1016/j.tins.2006.09.001
156. Brondino, N.; Re, S.; Boldrini, A.; Cuccomarino, A.; Lanati, N.; Barale, F.; Politi, P. Curcumin as a therapeutic agent in dementia: A mini systematic review of human studies Sci. World J. 2014, 2014, 174282 10.1155/2014/174282
157. Chandra, V.; Pandav, R.; Dodge, H. H.; Johnston, J. M.; Belle, S. H.; DeKosky, S. T.; Ganguli, M. Incidence of Alzheimer’s disease in a rural community in India: The Indo-US study Neurology 2001, 57, 985-989 10.1212/WNL.57.6.985
158. Ng, T.-P.; Chiam, P.-C.; Lee, T.; Chua, H.-C.; Lim, L.; Kua, E.-H. Curry consumption and cognitive function in the elderly Am. J. Epidemiol. 2006, 164, 898-906 10.1093/aje/kwj267
159. Li, S.; Yuan, W.; Deng, G.; Wang, P.; Yang, P.; Aggarwal, B. B. Chemical composition and product quality control of turmeric (Curcuma longa l.) Pharm. Crops 2011, 2, 28-54 10.2174/2210290601102010028
160. Clark, C. M.; Sheppard, L.; Fillinbaum, G. G.; Galasko, D.; Morris, J. C.; Koss, E.; Mohs, R.; Heyman, A. Variability in annual mini-mental state examination score in patients with probable Alzheimer’s disease Arch. Neurol. (Chicago) 1999, 56, 857-862 10.1001/archneur.56.7.857
161. Dahlin, J. L.; Walters, M. A. The essential roles of chemistry in high-throughput screening triage Future Med. Chem. 2014, 6, 1265-1290 10.4155/fmc.14.60
162. Atanasov, A. G.; Waltenberger, B.; Pferschy-Wenzig, E. M.; Linder, T.; Wawrosch, C.; Uhrin, P.; Temml, V.; Wang, L.; Schwaiger, S.; Heiss, E. H.; Rollinger, J. M.; Schuster, D.; Breuss, J. M.; Bochkov, V.; Mihovilovic, M. D.; Kopp, B.; Bauer, R.; Dirsch, V. M.; Stuppner, H. Discovery and resupply of pharmacologically active plant-derived natural products: A review Biotechnol. Adv. 2015, 33, 1582-1614 10.1016/j.biotechadv.2015.08.001
163. Wagner, H. Synergy research: Approaching a new generation of phytopharmaceuticals Fitoterapia 2011, 82, 34-37 10.1016/j.fitote.2010.11.016
164. Gertsch, J. The metabolic plant feedback hypothesis: How plant secondary metabolites nonspecifically impact human health Planta Med. 2016, 82, 920-929 10.1055/s-0042-108340