Curcumin - Properties, Applications and Modification of Structure

Author(s): Barbara Roman*, Monika Retajczyk, Łukasz Sałaciński, Robert Pełech

Journal Name: Mini-Reviews in Organic Chemistry

Volume 17 , Issue 5 , 2020

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Abstract:

In recent years, the interest in biologically active compounds of natural origin has increased significantly. Researchers' research focuses on increasing the activity of curcumin by forming complexes with metals such as vanadium, iron, copper or gallium. Introduction of metal compounds to curcumin increases the scope of application in pharmacology. The main direction of research development is the treatment of tumors, among others stomach cancer or leukemia. Curcuminoids are the main components of turmeric (Curcuma longa L.), a plant from India and South-East Asia. Due to its intense yellow-orange color and pleasant aroma, the powdered rootstalk is widely used in the food industry, as natural dye and spice. The chemical compound responsible for the characteristic color of rhizomes of curcuma is 1,6-heptadien-3,5-dione-1,7-bis(4-hydroxy-3-methoxyphenyl) - (1E, 6E) called curcumin. This work aims to characterize curcumin in terms of its structure, therapeutic properties and also as a substrate for the synthesis of valuable derivatives like tetrahydrocurcumin. Knowledge about this relationship based on literature analysis will enable a better understanding of the factors responsible for its biological activity.

Keywords: Chemical disintegration, chemoprevention, curcumin, diacetylcurcumin complexes, modification of structure, tautomerization.

[1]
Ravindran, P.N.; Nirmal-Babu, K.; Kandaswamy, S. Turmeric - The Golden Spice of Life. In: Turmeric - The Golden Spice of Life; CRC Press: Boca Raton, 2007; pp. 1-14.
[http://dx.doi.org/10.1201/9781420006322]
[2]
Kermanshahi, H.; Riasi, A. Effect of turmeric rhizome powder (Curcuma longa L.) and soluble NSP degrading enzyme on some blood parameters of laying hens. Int. J. Poult. Sci., 2006, 5, 494-498.
[http://dx.doi.org/10.3923/ijps.2006.494.498]
[3]
Aggarwal, B.B.; Sundaram, C.; Malani, N.; Ichikawa, H. Curcumin: The Indian solid gold. Adv. Exp. Med. Biol., 2007, 595, 1-75.
[http://dx.doi.org/10.1007/978-0-387-46401-5_1] [PMID: 17569205]
[4]
Tainter, D.R.; Grenis, A.T. Spices and Seasoning. A Food Technology Handbook, 2nd ed; Wiley-VCH: New York, 2001.
[5]
Islam, F.; Karim, M.R.; Shajahan, M. Study on the effect of plant spacing on the production of turmeric at farmer’s field. Asian J. Plant Sci., 2002, 1(6), 616-617.
[http://dx.doi.org/10.3923/ajps.2002.616.617]
[6]
Lal, J. Turmeric, curcumin and our life: A review. Bull. Environ. Pharmacol. Life Sci., 2012, 1(7), 11-17.
[7]
Naz, S.; Ilyas, S.; Parveen, Z.; Javed, S. Chemical analysis of essentials oils from turmeric (Curcuma longa L.) rhizome through GC-MS. Asian J. Chem., 2010, 22, 3153-3158.
[8]
Miłobędzka, J.; Kostanecki, St.; Lampe, V. Zur Kenntnis des Curcumins. Ber. Dtsch. Chem. Ges., 1910, 43(2), 2163-2170.
[http://dx.doi.org/10.1002/cber.191004302168]
[9]
Szczepański, M.A.; Grzanka, A. Chemopreventive and anti-cancer properties of curcumin. J. Oncol., 2009, 59(5), 377-384.
[10]
Joe, B.; Vijaykumar, M.; Lokesh, B.R. Biological properties of curcumin-cellular and molecular mechanisms of action. Crit. Rev. Food Sci. Nutr., 2004, 44(2), 97-111.
[http://dx.doi.org/10.1080/10408690490424702] [PMID: 15116757]
[11]
Shen, L.; Ji, H.F. Theoretical study on physicochemical properties of curcumin. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2007, 67(3-4), 619-623.
[http://dx.doi.org/10.1016/j.saa.2006.08.018] [PMID: 16979936]
[12]
Kiuchi, F.; Goto, Y.; Sugimoto, N.; Akao, N.; Kondo, K.; Tsuda, Y. Nematocidal activity of turmeric: Synergistic action of curcuminoids. Chem. Pharm. Bull. (Tokyo), 1993, 41(9), 1640-1643.
[http://dx.doi.org/10.1248/cpb.41.1640] [PMID: 8221978]
[13]
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(12), 1867-1876.
[http://dx.doi.org/10.1016/S0731-7085(96)02024-9] [PMID: 9278892]
[14]
Delgado-Vargas, F.; Paredes-Lopez, O. Natural Colorants for Food and Nutraceutical Uses; CRC Press: Boca Raton, 2003, pp. 239-243.
[15]
Singh, S.; Aggarwal, B.B. Activation of transcription factor NF-κ B is suppressed by curcumin (diferuloylmethane). J. Biol. Chem., 1995, 270(42), 24995-25000.
[http://dx.doi.org/10.1074/jbc.270.42.24995] [PMID: 7559628]
[16]
Chiocca, E.A.; Waxman, D.J. Cytochrome p450-based gene therapies for cancer. Methods Mol. Med., 2004, 90, 203-222.
[PMID: 14657565]
[17]
Lee, J.S.; Surh, Y.J. Nrf2 as a novel molecular target for chemoprevention. Cancer Lett., 2005, 224(2), 171-184.
[http://dx.doi.org/10.1016/j.canlet.2004.09.042] [PMID: 15914268]
[18]
Singh, S.V.; Hu, X.; Srivastava, S.K.; Singh, M.; Xia, H.; Orchard, J.L.; Zaren, H.A. Mechanism of inhibition of benzo[a]pyrene-induced forestomach cancer in mice by dietary curcumin. Carcinogenesis, 1998, 19(8), 1357-1360.
[http://dx.doi.org/10.1093/carcin/19.8.1357] [PMID: 9744529]
[19]
Brouet, I.; Ohshima, H. Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem. Biophys. Res. Commun., 1995, 206(2), 533-540.
[http://dx.doi.org/10.1006/bbrc.1995.1076] [PMID: 7530002]
[20]
Aggarwal, S.; Ichikawa, H.; Takada, Y.; Sandur, S.K.; Shishodia, S.; Aggarwal, B.B. Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation. Mol. Pharmacol., 2006, 69(1), 195-206.
[http://dx.doi.org/10.1124/mol.105.017400] [PMID: 16219905]
[21]
Bae, J.H.; Park, J.W.; Kwon, T.K. Ruthenium red, inhibitor of mitochondrial Ca2+ uniporter, inhibits curcumin-induced apoptosis via the prevention of intracellular Ca2+ depletion and cytochrome c release. Biochem. Biophys. Res. Commun., 2003, 303(4), 1073-1079.
[http://dx.doi.org/10.1016/S0006-291X(03)00479-0] [PMID: 12684045]
[22]
Woo, J.H.; Kim, Y.H.; Choi, Y.J.; Kim, D.G.; Lee, K.S.; Bae, J.H.; Min, D.S.; Chang, J.S.; Jeong, Y.J.; Lee, Y.H.; Park, J.W.; Kwon, T.K. Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis, 2003, 24(7), 1199-1208.
[http://dx.doi.org/10.1093/carcin/bgg082] [PMID: 12807727]
[23]
Bush, J.A.; Cheung, K.J., Jr; Li, G. Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53. Exp. Cell Res., 2001, 271(2), 305-314.
[http://dx.doi.org/10.1006/excr.2001.5381] [PMID: 11716543]
[24]
Huang, M.T.; Lysz, T.; Ferraro, T.; Abidi, T.F.; Laskin, J.D.; Conney, A.H. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Res., 1991, 51(3), 813-819.
[PMID: 1899046]
[25]
Jobin, C.; Bradham, C.A.; Russo, M.P.; Juma, B.; Narula, A.S.; Brenner, D.A.; Sartor, R.B. Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. J. Immunol., 1999, 163(6), 3474-3483.
[PMID: 10477620]
[26]
Sharma, R.A.; Gescher, A.J.; Steward, W.P. Curcumin: the story so far. Eur. J. Cancer, 2005, 41(13), 1955-1968.
[http://dx.doi.org/10.1016/j.ejca.2005.05.009] [PMID: 16081279]
[27]
Notoya, M.; Nishimura, H.; Woo, J.T.; Nagai, K.; Ishihara, Y.; Hagiwara, H. Curcumin inhibits the proliferation and mineralization of cultured osteoblasts. Eur. J. Pharmacol., 2006, 534(1-3), 55-62.
[http://dx.doi.org/10.1016/j.ejphar.2006.01.028] [PMID: 16476424]
[28]
Arbiser, J.L.; Klauber, N.; Rohan, R.; van Leeuwen, R.; Huang, M.T.; Fisher, C.; Flynn, E.; Byers, H.R. Curcumin is an in vivo inhibitor of angiogenesis. Mol. Med., 1998, 4(6), 376-383.
[http://dx.doi.org/10.1007/BF03401744] [PMID: 10780880]
[29]
Sreejayan, N.; Rao, M.N.A. Nitric oxide scavenging by curcuminoids. J. Pharm. Pharmacol., 1997, 49(1), 105-107.
[http://dx.doi.org/10.1111/j.2042-7158.1997.tb06761.x] [PMID: 9120760]
[30]
Toda, S.; Miyase, T.; Arichi, H.; Tanizawa, H.; Takino, Y. Natural antioxidants. III. Antioxidative components isolated from rhizome of Curcuma longa L. Chem. Pharm. Bull. (Tokyo), 1985, 33(4), 1725-1728.
[31]
Kędzia, B.; Hołderna-Kędzia, E. Antimicrobial effect of plant phenol derivatives. Postepy Fitoter., 2012, 3, 151-155.
[32]
Kim, D.C.; Kim, S.H.; Choi, B.H.; Baek, N.I.; Kim, D.; Kim, M.J.; Kim, K.T. Curcuma longa extract protects against gastric ulcers by blocking H2 histamine receptors. Biol. Pharm. Bull., 2005, 28(12), 2220-2224.
[http://dx.doi.org/10.1248/bpb.28.2220] [PMID: 16327153]
[33]
Thakur, R.; Puri, H.S.; Husain, A. Major Medical Plants of India; Central Institute of Medicinal and Aromatic Plants: Lucknow, 1989.
[34]
Bengmark, S.; Mesa, M.D.; Gil, A. Plant-derived health: the effects of turmeric and curcuminoids. Nutr. Hosp., 2009, 24(3), 273-281.
[PMID: 19721899]
[35]
Jayaprakasha, G.K.; Jagan-Mohan-Rao, L.; Sakariah, K.K. Chemistry and biological activities of C. longa. Trends Food Sci. Technol., 2005, 16, 533-548.
[http://dx.doi.org/10.1016/j.tifs.2005.08.006]
[36]
Tada, H.; Ikeda, Y.; Omoto, T.; Shimomura, K.; Ishimaru, K. Rosmarinic acid and related phenolics inmadventitius root cultures of Ocimum basilicum L. Plant Tissue Cult. Lett., 1996, 13(1), 69-71.
[http://dx.doi.org/10.5511/plantbiotechnology1984.13.69]
[37]
Gupta, S.C.; Sung, B.; Kim, J.H.; Prasad, S.; Li, S.; Aggarwal, B.B. Multitargeting by turmeric, the golden spice: From kitchen to clinic. Mol. Nutr. Food Res., 2013, 57(9), 1510-1528.
[http://dx.doi.org/10.1002/mnfr.201100741] [PMID: 22887802]
[38]
Sternini, C.; Reeve, J.R., Jr; Brecha, N. Distribution and characterization of calcitonin gene-related peptide immunoreactivity in the digestive system of normal and capsaicin-treated rats. Gastroenterology, 1987, 93(4), 852-862.
[http://dx.doi.org/10.1016/0016-5085(87)90450-1] [PMID: 3305137]
[39]
Zaidi, A.; Lai, M.; Cavenagh, J. Long-term stabilization of myloma with curcumin. BMJ Case Rep., 2017, 2017, bcr2016218148.
[40]
Cheng, A.L.; Hsu, C.H.; Lin, J.K.; Hsu, M.M.; Ho, Y.F.; Shen, T.S.; Ko, J.Y.; Lin, J.T.; Lin, B.R.; Ming-Shiang, W.; Yu, H.S.; Jee, S.H.; Chen, G.S.; Chen, T.M.; Chen, C.A.; Lai, M.K.; Pu, Y.S.; Pan, M.H.; Wang, Y.J.; Tsai, C.C.; Hsieh, C.Y. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res., 2001, 21(4B), 2895-2900.
[PMID: 11712783]
[41]
Sikora-Polaczek, M.; Bielak-Żmijewska, A.; Sikora, E. Molecular and cellular mechanisms of actioncurcumin - a beneficial effect on the body. Postepy Biochem., 2011, 57(1), 74-84.
[PMID: 21735822]
[42]
Basnet, P.; Skalko-Basnet, N. Curcumin: An anti-inflammatory molecule from a curry spice on the path to cancer treatment. Molecules, 2011, 16(6), 4567-4598.
[http://dx.doi.org/10.3390/molecules16064567] [PMID: 21642934]
[43]
Anand, P.; Kunnumakkara, A.B.; Newman, R.A.; Aggarwal, B.B. Bioavailability of curcumin: Problems and promises. Mol. Pharm., 2007, 4(6), 807-818.
[http://dx.doi.org/10.1021/mp700113r] [PMID: 17999464]
[44]
Jithan, A.; Madhavi, K.; Madhavi, M.; Prabhakar, K. Preparation and characterization of albumin nanoparticles encapsulating curcumin intended for the treatment of breast cancer. Int. J. Pharm. Investig., 2011, 1(2), 119-125.
[http://dx.doi.org/10.4103/2230-973X.82432] [PMID: 23071931]
[45]
Bakhru, H.K. Herbs that heal: natural remedies for good health; Orient Paperbacks: New Delhi, 1997, pp. 164-166.
[46]
Sowbhagya, H.B.; Smitha, S.; Sampathu, S.R. Stability of water-soluble turmeric colourant in an extruded food product during storage. J. Food Eng., 2005, 67, 367-371.
[http://dx.doi.org/10.1016/j.jfoodeng.2004.05.003]
[47]
Scotter, M.J. Synthesis and chemical characterisation of cur-cuminoid colouring principles for their potential use as HPLC standards for the determination of curcumin colour in foods. Food Sci. Technol., 2009, 42, 1345-1351.
[48]
EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Scientific opinion on the re-evaluation of curcumin (E 100) as a food additive. EFSA J., 2010, 8, 1679.
[49]
Payton, F.; Sandusky, P.; Alworth, W.L. NMR study of the solution structure of curcumin. J. Nat. Prod., 2007, 70(2), 143-146.
[http://dx.doi.org/10.1021/np060263s] [PMID: 17315954]
[50]
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(50), 14533-14540.
[http://dx.doi.org/10.1021/jp3050516] [PMID: 23194397]
[51]
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(2), 1114-1124.
[http://dx.doi.org/10.1074/jbc.M110.178806] [PMID: 21071447]
[52]
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(2), 116-122.
[http://dx.doi.org/10.1007/BF01041928] [PMID: 3765852]
[53]
Hamaguchi, T.; Ono, K.; Yamada, M. REVIEW: Curcumin and Alzheimer’s disease. CNS Neurosci. Ther., 2010, 16(5), 285-297.
[http://dx.doi.org/10.1111/j.1755-5949.2010.00147.x] [PMID: 20406252]
[54]
Kumar, A.; Dogra, S.; Prakash, A. Protective effect of curcumin (Curcuma longa), against aluminium toxicity: Possible behavioral and biochemical alterations in rats. Behav. Brain Res., 2009, 205(2), 384-390.
[http://dx.doi.org/10.1016/j.bbr.2009.07.012] [PMID: 19616038]
[55]
Deptuła, T. Effect of Polyether Substituents on the Biological Activity of Curcumin Analogs. PhD Thesis, Warsaw University Faculty of Chemistry, Warsaw, 2016.
[56]
Murugan, P.; Pari, L. Antioxidant effect of tetrahydrocurcumin in streptozotocin-nicotinamide induced diabetic rats. Life Sci., 2006, 79(18), 1720-1728.
[http://dx.doi.org/10.1016/j.lfs.2006.06.001] [PMID: 16806281]
[57]
Sugiyama, Y.; Kawakishi, S.; Osawa, T. Involvement of the β -diketone moiety in the antioxidative mechanism of tetrahydrocurcumin. Biochem. Pharmacol., 1996, 52(4), 519-525.
[58]
Jordan, B.C.; Kumar, B.; Thilagavathi, R.; Yadhav, A.; Kumar, P.; Selvam, C. Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms. Chem. Biol. Drug Des., 2018, 91(1), 332-337.
[http://dx.doi.org/10.1111/cbdd.13061] [PMID: 28649799]
[59]
Liu, B.; Xia, M.; Ji, X.; Xu, L.; Dong, J. Synthesis and antiproliferative effect of novel curcumin analogues. Chem. Pharm. Bull. (Tokyo), 2013, 61(7), 757-763.
[http://dx.doi.org/10.1248/cpb.c13-00295] [PMID: 23666373]
[60]
Deptuła, T.; Gruber, B.; Krówczyński, A. Curcumin and its derivatives - use in cancer and chemoprotective therapy. Postepy Fitoter., 2014, 3, 155-165.
[61]
Sahu, P.K.; Sahu, P.K.; Sahu, P.L.; Agarwal, D.D. Structure activity relationship, cytotoxicity and evaluation of antioxidant activity of curcumin derivatives. Bioorg. Med. Chem. Lett., 2016, 26(4), 1342-1347.
[http://dx.doi.org/10.1016/j.bmcl.2015.12.013] [PMID: 26810315]
[62]
Barreto, R.; Kawakita, S.; Tsuchiya, J.; Minelli, E.; Pavasuthipaisit, K.; Helmy, A.; Marotta, F. Metal-induced oxidative damage in cultured hepatocytes and hepatic lysosomal fraction: beneficial effect of a curcumin/absinthium compound. Chin. J. Dig. Dis., 2005, 6(1), 31-36.
[http://dx.doi.org/10.1111/j.1443-9573.2005.00184.x] [PMID: 15667556]
[63]
Campbell, A.; Smith, M.A.; Sayre, L.M.; Bondy, S.C.; Perry, G. Mechanisms by which metals promote events connected to neurodegenerative diseases. Brain Res. Bull., 2001, 55(2), 125-132.
[http://dx.doi.org/10.1016/S0361-9230(01)00455-5] [PMID: 11470308]
[64]
Benassi, R.; Ferrari, E.; Grandi, R.; Lazzari, S.; Saladini, M. Synthesis and characterization of new β-diketo derivatives with iron chelating ability. J. Inorg. Biochem., 2007, 101(2), 203-213.
[http://dx.doi.org/10.1016/j.jinorgbio.2006.09.020] [PMID: 17097145]
[65]
Rouault, T.A. Iron on the brain. Nat. Genet., 2001, 28(4), 299-300.
[http://dx.doi.org/10.1038/91036] [PMID: 11479580]
[66]
Thephinlap, C.; Phisalaphong, C.; Fucharoen, S.; Porter, J.B.; Srichairatanakool, S. Efficacy of curcuminoids in alleviation of iron overload and lipid peroxidation in thalassemic mice. Med. Chem., 2009, 5(5), 474-482.
[http://dx.doi.org/10.2174/157340609789117912] [PMID: 19534681]
[67]
Kohlmunzer, S. Pharmacognosy - A Textbook for Pharmacy Students, 5th ed; PZWL: Warszawa, 2007.
[68]
Wanninger, S.; Lorenz, V.; Subhan, A.; Edelmann, F.T. Metal complexes of curcumin--synthetic strategies, structures and medicinal applications. Chem. Soc. Rev., 2015, 44(15), 4986-5002.
[http://dx.doi.org/10.1039/C5CS00088B] [PMID: 25964104]
[69]
Hee-Je, K.; Dong-Jo, K.; Karthick, S.N.; Hemalatha, K.V.; Raj, C.J.; Sunseong, O.; Youngson, C. Curcumin dye extracted from Curcuma longa L. used as sensitizers for efficient dye-sensitized solar cells. Int. J. Electrochem. Sci., 2013, 8, 8320-8328.
[70]
Mohammadi, K.; Thompson, K.H.; Patrick, B.O.; Storr, T.; Martins, C.; Polishchuk, E.; Yuen, V.G.; McNeill, J.H.; Orvig, C. Synthesis and characterization of dual function vanadyl, gallium and indium curcumin complexes for medicinal applications. J. Inorg. Biochem., 2005, 99(11), 2217-2225.
[http://dx.doi.org/10.1016/j.jinorgbio.2005.08.001] [PMID: 16171869]
[71]
John, V.D.; Krishnankutty, K. Antitumour activity of synthetic curcuminoid analogues (1,7- diaryl-1,6-heptadiene-3,5-diones) and their copper Complexes. Appl. Organomet. Chem., 2006, 20, 477-482.
[http://dx.doi.org/10.1002/aoc.1089]
[72]
Mohamed, R.W.; Mohamed, T.E.; Moram, G.S.E.; Badawy, A.M.; Zaky, M.F. Comparative study on the effect of nano-curcumin complexes as antitumor in mice. World J. Pharm. Res., 2018, 7(19), 1404-1436.
[73]
Lim, S.; Park, H.; Ghafoor, K. Quality and antioxidant proper-ties of bread containing turmeric (Curcuma longa L.) cultivated in South Korea. Food Chem., 2011, 124, 1577-1582.
[http://dx.doi.org/10.1016/j.foodchem.2010.08.016]


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VOLUME: 17
ISSUE: 5
Year: 2020
Published on: 11 August, 2020
Page: [486 - 495]
Pages: 10
DOI: 10.2174/1570193X16666190621110247
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