Curcumin: A Culinary Herb and Its Health Benefits
DOI:
https://doi.org/10.12970/2308-8044.2013.01.01.1Keywords:
NFkB, inflammation, heme-oxygenase, antioxidant, brain, Alzheimer’s disease, apoptosis, cardiovascular protection, cancer.Abstract
Curcumin, present in Curcuma longa, a traditional Indian spice, has many important biological mechanisms to improve health of aging organisms. It inhibits nuclear factor kappa beta (NFkB) decreasing both inflammation and cell survival, which is important to avoid proliferation of cancer cells and decrease brain, endothelial and myocardial damage. Curcumin also decreases inflammation by other membrane systems, such as protein kinases. This traditional spice also elicites higher antioxidant activity that can potentially enhance neuronal survival, decreasing the risk of neurodegenerative disorders of the CNS (e.g. Alzheimer’s disease). By its capability to trigger apoptosis of different target tumoral cells, curcumin has been considered as a new promise anti-cancer quimiopreventive agent. It is speculated that dietary curcumin could perform many important biological mechanisms affording a better quality of life during human lifespan.
References
Gupta SC, Sung B, Kim JH, Prasad S, Li S, Aggarwal BB. Multitargeting by turmeric, the golden spice: From kitchen to clinic. Mol Nutr Food Res 2012. http://dx.doi.org/10.1002/mnfr.201100741
Li SY, Yuan W, Deng GR, Wang P. et al., Chemical composition and product quality control of turmeric (Curcuma longa L.). Pharm Crops 2011; 2: 28-54. http://dx.doi.org/10.2174/2210290601102010028
Pfeiffer E, Hhle S, Solyom A, Metzler M. Studies on the stability of turmeric constituents. J. Food Engineer 2003; 56: 257-59. http://dx.doi.org/10.1016/S0260-8774(02)00264-9
Khalil OAK, Oliveira OMMF, Vellosa JCR, Quadros AU, Dalposso LM, Karam TK, et al. Curcumin antifungal and antioxidant activities are increased in the presence of ascorbic acid. Food Chem 2012; 133: 1001-1005. http://dx.doi.org/10.1016/j.foodchem.2012.02.009
Fu Y, Zheng S, Lin J, Ryerse J, Chen A. Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. Mol Pharmacol 2008; 73: 399-409. http://dx.doi.org/10.1124/mol.107.039818
Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 1993; 90: 7915-22. http://dx.doi.org/10.1073/pnas.90.17.7915
Ferrari CKB, Franca EL, Honorio-Franca AC. Nitric oxide, health and disease. J Appl Biomed 2009; 7(4): 163-73.
Ahmad T, Aggarwal K, Pattnaik B, Mukherjee S, Sethi T, Tiwari BK, et al. Computational classification of mitochondrial shapes reflects stress and redox state. Cell Death and Disease 2013; 4: e461. http://dx.doi.org/10.1038/cddis.2012.213
Shishodia S, Sethi G, Aggarwal BB. Curcumin: getting back to the roots. Ann NY Acad Sci 2005; 1056: 206-17. http://dx.doi.org/10.1196/annals.1352.010
Anantharaju A, Feller A, Chedid A. Aging liver. A review. Gerontology 2002; 48: 343-53. http://dx.doi.org/10.1159/000065506
Balasubramanyam M, Koteswari AA, Kumar RS, Monickaraj SF, Maheswari JU, Mohan V. Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications. J Biosci 2003; 28: 715-21. http://dx.doi.org/10.1007/BF02708432
Miquel J, Martinez M, Díez A, De Juan E, Soler A, Ramirez A, et al. Effects of turmeric on blood and liver lipoperoxide levels of mice: lack of toxicity. AGE 1995; 18: 171-4. http://dx.doi.org/10.1007/BF02432632
Asai A, Nakagawa K, Miyazawa T. Antioxidative effects of turmeric, rosemary, and capsicum extracts on membrane phospholipid peroxidation and liver lipid metabolism in mice. Biosci Biotechnol Biochem 1999; 63: 2118-22. http://dx.doi.org/10.1271/bbb.63.2118
Paolinelli ST, Reen R, Moraes-Santos T. Curcuma longa ingestion protects against in vitro hepatocyte membrane peroxidation. Rev Bras Ciênc Farm 2006; 42: 429-35.
Wei QY, Chen WF, Zhou B, Yang L, Liu ZL. Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues. Biochim Biophys Acta 2006; 1760: 70-7.
Naik SR, Thakare VN, Pati SR. Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: Evidence of its antioxidant property. Exper Toxicol Pathol 2011; 63: 419-31. http://dx.doi.org/10.1016/j.etp.2010.03.001
Elaziz EAA, Ibrahim ZS, Elkattawy AM. Protective effect of Curcuma longa against CCl4 induced oxidative stress and cellular degeneration in rats. Global Vet 2010; 5(5): 272-81.
Nirmala C, Anand S, Puvanakrishnan R. Curcumin treatment modulates collagen metabolism in isopreterenol induced myocardial necrosis in rats. Mol Cel Biochem 1999; 197: 31- 37. http://dx.doi.org/10.1023/A:1006960106929
Bosca AR, Guttierrez MAC, Soler A, Puerta C, Diez A, Quintanilla E, et al. Effects of the antioxidant turmeric on lipoprotein peroxides: implications for the prevention of atherosclerosis. AGE 1997; 20: 165-8. http://dx.doi.org/10.1007/s11357-997-0015-z
Yang X, Thomas DP, Zhang X, Culver BW, Alexander BM, Murdoch WJ, et al. Curcumin inhibits platelet-derived growth factor-stimulated vascular smooth muscle cell function and injury-induced neointima formation. Arterioscler Thromb Vasc Biol 2006; 26: 85-90. http://dx.doi.org/10.1161/01.ATV.0000191635.00744.b6
Tedgui A, Mallat Z. Smooth muscle cells. Another source of tissue factor-containing microparticles in atherothrombosis? Circ Res 2000; 87: 81. http://dx.doi.org/10.1161/01.RES.87.2.81
Mertens A, Holvoet P. Oxidized LDL and HDL: antagonists in atherothrombosis. FASEB J 2001; 15: 2073-84. http://dx.doi.org/10.1096/fj.01-0273rev
Quiles JL, Mesa MD, Ramírez-Tortosa CL, Aguilera CM, Battino M, Gil A, et al. Curcuma longa extract supplementation reduces oxidative stress and attenuates aortic fatty streak development in rabbits. Arterioscler Thromb Vasc Biol 2002; 22: 1225-31. http://dx.doi.org/10.1161/01.ATV.0000020676.11586.F2
Gross S, Tilly P, Henstsch D, Vonesch J-L, Fabre J-E. Vascular wall-produced prostaglandin E2 exacerbates arterial thrombosis and atherothrombosis through platelet EP3 receptors. J Exp Med 2007; 204: 311-20. http://dx.doi.org/10.1084/jem.20061617
Manson MM, Holloway KA, Howells LM, Hudson EA, Plummer SM, Squires MS, et al. Modulation of signaltransduction pathways by chemopreventive agents. Biochem Soc Transact 2000; 28: 7-12.
Bengmark S. Curcumin, an atoxic antioxidant and natural NFkB, cyclooxigenase-2, lipooxigenase, and inducible nitricoxide synthase inhibitor: a shield against acute and chronic diseases. J Parent Ent Nutr 2006; 30: 45-51. http://dx.doi.org/10.1177/014860710603000145
Kim D-C, Ku S-K, Bae J-S. Anticoagulant activities of curcumin and its derivative. BMB Rep 2012; 45: 221-26. http://dx.doi.org/10.5483/BMBRep.2012.45.4.221
Yang Y, Duan W, Liang Z, Yi W, Yan J, Wang N, et al. Curcumin attenuates endothelial cell oxidative stress injury through Notch signaling inhibition. Cell Signal 2013; 25: 615- 29. http://dx.doi.org/10.1016/j.cellsig.2012.11.025
Wongcharoen W, Jai-Aue S, Phrommintikul A, Nawarawong W, Woragidpoonpol S, Tepsuwan T, et al. Effects of curcuminoids on frequency of acute myocardial infarction after coronary artery bypass grafting. Am J Cardiol 2012; 110: 40-44. http://dx.doi.org/10.1016/j.amjcard.2012.02.043
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. http://dx.doi.org/10.1093/aje/kwj267
Bala K, Tripathy B, Sharma D. Neuroprotective and antiaging effects of curcumin in aged rat brain regions. Biogerontology 2006; 7: 81-9. http://dx.doi.org/10.1007/s10522-006-6495-x
Wang Q, Sun AY, Simonyi A, Jensen MD, Shelat PB, Rottinghaus GE, et al. Neuroprotective mechanisms of curcumin against-cerebral ischemia-induced neuronal apoptosis and behavioral deficits. J Neurosci Res 2005; 82: 138-48. http://dx.doi.org/10.1002/jnr.20610
Zhu Y-G, Chen X-C, Chen Z-Z, Zeng Y-Q, Shi G-B, Su Y-H, et al. Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons. Acta Pharmacol Sin 2004; 25: 1606-12.
Zhao J, Yu S, Zheng W, Feng G, Luo G, Wang L, et al. Curcumin improves outcomes and attenuates focal cerebral ischemic injury via antiapoptotic mechanisms in rats. Neurochem Res 2010; 35: 374-79. http://dx.doi.org/10.1007/s11064-009-0065-y
Jagatha B, Mythri RB, Vali S, Bharath MMS. Curcumin treatment alleviates the effects of glutathione depletion in vitro and in vivo: Therapeutic implications for Parkinson’s disease and explained via in silico studies. Free Rad Biol Med 2008; 44: 907-17. http://dx.doi.org/10.1016/j.freeradbiomed.2007.11.011
Stridh MH, Correa F, Nodin C, Weber SG, Blomstrand F, Nilsson M, et al. Enhanced glutathione efflux from astrocytes in culture by low extracellular Ca2+ and curcumin. Neurochem Res 2010; 35: 1231-38. http://dx.doi.org/10.1007/s11064-010-0179-2
Pan J, Li H, Ma J-F, Tan Y-Y, Xiao Q, Ding J-Q, et al. Curcumin inhibition of JNKs prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease through suppressing mitochondria dysfunction. Transl Neurodegener 2012; 1: 16. http://dx.doi.org/10.1186/2047-9158-1-16
Cemil B, Topuz K, Demircan MN, Kurt G, Tun K, Kutlay M, et al. Curcumin improves early functional results after experimental spinal cord injury. Acta Neurochir 2010; 152: 1583-90. http://dx.doi.org/10.1007/s00701-010-0702-x
Otterbein LE, Choi AMK. Heme oxygenase: colors of defense agaisnt cellular stress. Am J Physiol 2000; 279: L1029-L37.
Chang EF, Wong RJ, Vreman HJ, Igarashi T, Galo E, Sharp FR, et al. Heme-oxygenase-2 protects against lipid peroxidation-mediated cell loss and impaired motor recovery after traumatic brain injury. J Neurosci 2003; 23: 3689-96.
Poon HF, Calabrese V, Scapagnini G, Butterfield A. Free radicals: key to brain aging and heme oxygenase as a cellular response to oxidative stress. J Gerontol A Biol Sci Med Sci 2004; 59: M478-M93. http://dx.doi.org/10.1093/gerona/59.5.M478
Scapagnini G, Foresti R, Calabrese V, Stella AMG, Green CJ, Motterlini R. Caffeic acid phenetyl ester and curcumin: A novel class of Heme oxygenase-1 inducers. Mol Pharmacol 2002; 61: 554-61. http://dx.doi.org/10.1124/mol.61.3.554
Scapagnini G, Colombrita C, Amadio M, D’Agata V, Arcelli E, Sapienza M, et al. Curcumin activates defensive genes and protects neurons against oxidative stress. Antiox Red Signal 2006; 8: 395-403. http://dx.doi.org/10.1089/ars.2006.8.395
Smith MA, Rottkamp CA, Nunomura A, Raina AK, Perry G. Oxidative stress in Alzheimer´s disease. Biochim Biophys Acta 2000; 1502: 139-44. http://dx.doi.org/10.1016/S0925-4439(00)00040-5
Keil U, Bonert A, Marques CA, Scherping I, Weyermann J, Strosznajder JB, et al. Amyloid -induced changes in nitric oxide production and mitochondrial activity lead to apoptosis. J Biol Chem 2004; 279: 50310-20. http://dx.doi.org/10.1074/jbc.M405600200
Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 2001; 21: 8370-7.
Ono K, Hasegawa K, Naiki H, Yamada M. Curcumin has potent anti-amyloidogenic effects for Alzheimer’s-amyloid fibrils in vitro. J Neurosci Res 2004; 75: 742-50. http://dx.doi.org/10.1002/jnr.20025
Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, et al. Curcumin inhibits formation of amyloid oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 2005; 280: 5892-901. http://dx.doi.org/10.1074/jbc.M404751200
Jiang T, Zhi X-L, Zhang Y-H, Pan L-F, Zhou P. Inhibitory effect of curcumin on the Al(III)-induced A 42 aggregation and neurotoxicity in vitro. Biochim Biophys Acta 2012; 1822: 1207-15.
Awasthi S, Srivatava SK, Piper JT, Singhal SS, Chaubey M, Awasthi YC. Curcumin protects against 4-hydroxy-2-transnonenal-induced cataract formation in rat lenses. Am J Clin Nutr 1996; 64: 761-6.
Suryanarayana P, Krishnaswamy K, Reddy GB. Effect of curcumin on galactose-induced cataractogenesis in rats. Mol Vis 2003; 9: 223-30.
Suryanarayana P, Saraswat M, Mrudula T, Krisna P, Krishnaswamy K, Reddy GB. Curcumin and turmeric delay streptozotocin-induced diabetic cataract in rats. Invest Ophthalmol Vis Sci 2005; 46: 2092-9. http://dx.doi.org/10.1167/iovs.04-1304
Osawa T, Kato Y. Protective role of antioxidative food factors in oxidative stress caused by hyperglicemia. Ann NY Acad Sci 2005; 1043: 440-51. http://dx.doi.org/10.1196/annals.1333.050
Manikandan A, Thiagarajan R, Beulaja, S, Sudhandiran G, Arumugam M. Effect of curcumin on selenite-induced cataractogenesis in Wistar rat pups. Curr Eye Res 2010; 35(2): 122-29. http://dx.doi.org/10.3109/02713680903447884
Manikandan A, Thiagarajan R, Beulaja, S, Sudhandiran G, Arumugam M. Curcumin prevents free radical-mediated cataractogenesis through modulations in lens calcium. Free Rad Biol Med 2010; 48(4): 483-92. http://dx.doi.org/10.1016/j.freeradbiomed.2009.11.011
Radha A, Rukhmini SD, Vilasini S, Sakunthala PR, Sreedharan B, Velayudhan MP, et al. Bioactive derivatives ofcurcumin attenuate cataract formation in vitro. Chem Biol Drug Des 2012; 80(6): 887-92. http://dx.doi.org/10.1111/cbdd.12021
Kuo ML, Huang TS, Lin JK. Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells. Biochim Biophys Acta 1996; 1317: 95-100. http://dx.doi.org/10.1016/S0925-4439(96)00032-4
Majumdar APN, Banerjee S, Nautiyal J, Patel BB, Patel V, Du J, et al. Curcumin synergizes with resveratrol to inhibit colon cancer. Nutr Cancer 2009; 61: 544-53. http://dx.doi.org/10.1080/01635580902752262
Ghosh AK, Kay NE, Secreto CR, Shanafelt TD. Curcumin inhibits prosurvival pathways in chronic lymphocytic leukemia B Cells and may overcome their stromal protection in combination with EGCG. Clin Canc Res 2009; 15: 1250-58. http://dx.doi.org/10.1158/1078-0432.CCR-08-1511
Lee SJ, Langhans SA. Anaphase-promoting complex/ cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis. BMC Cancer 2012; 12: 44. http://dx.doi.org/10.1186/1471-2407-12-44
Ye MX, Zhao Y-L, Li Y, Miao Q, Li Z-K, Rena X-L, et al. Curcumin reverses cis-platin resistance and promotes human lung adenocarcinoma A549/DDP cell apoptosis through HIF1 and caspase-3. Phytomedicine 2012; 19: 779-87. http://dx.doi.org/10.1016/j.phymed.2012.03.005
Wang W-Z, Li L, Liu M-Y, Jin X-B, Mao J-W, Pu Q-H, et al. Curcumin induces FasL-related apoptosis through p38 activation in human hepatocellular carcinoma Huh7 cells. Life Sci 2013; 92: 352-58. http://dx.doi.org/10.1016/j.lfs.2013.01.013
Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, et al. Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/ progression stages of colon cancer. Cancer Res 1999; 59: 597-601.
Piwocka K, Bielak-Mijewska A, Sikora E. Curcumin induces caspase-3-independent apoptosis in human multidrugresistant cells. Ann NY Acad Sci 2002; 973: 250-4. http://dx.doi.org/10.1111/j.1749-6632.2002.tb04643.x
Deeb D, Xu YX, Jiang H, Gao X, Janakiraman N, Chapman RA, et al. Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells. Mol Cancer Ther 2003; 2: 95-103.
Bharti AC, Donato N, Singh S, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and ikappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 2003; 101: 1053-62. http://dx.doi.org/10.1182/blood-2002-05-1320
Syng-Ai C, Kumari AL, Khar A. Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2. Mol Cancer Ther 2004; 3: 1101-8.
Jung EM, Lim JH, Lee TJ, Park JW, Choi KS, Kwon TK. Curcumin sensitizes tumor necrosis factor-related apoptosisinducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5). Carcinogenesis 2005; 26: 1905-13. http://dx.doi.org/10.1093/carcin/bgi167
Lo Tempio MM, Veena MS, Steele HL, Ramamurthy B, Ramalingam TS, Cohen AN, et al. Curcumin suppresses the growth of head and neck squamous cell carcinoma. Clin Canc Res 2005; 11: 6994-7002. http://dx.doi.org/10.1158/1078-0432.CCR-05-0301
Moussavi M, Assi K, Gómez-Muñoz A, Salh B. Curcumin mediates ceramide generation via de novo pathway in colon cancer cells. Carcinogenesis 2006; 27: 1636-44. http://dx.doi.org/10.1093/carcin/bgi371
Barnes PJ, Karin M. Nuclear Factor-kB - a pivotal transcription factor in chronic inflammatory diseases. New Engl J Med 1997; 336: 1066-71. http://dx.doi.org/10.1056/NEJM199704103361506
Paniago EN, Ferrari CKB. Revisiting the pathology of the Nuclear Factor Kappa Beta. Intern J Biol Chem 2011; 5(5): 291-99. http://dx.doi.org/10.3923/ijbc.2011.291.299
Koedel U, Bayerlein I, Paul R, Sporer B, Pfister HW. Pharmacologic interference with NF-kB activation attenuates central nervous system complications in experimental pneumococcal meningitis. J Infect Dis 2000; 182: 1437-45. http://dx.doi.org/10.1086/315877
Lappas M, Permezel M, Georgiou HM, Rice GE. Nuclear Factor Kappa B regulation of proinflammatory cytokines in human gestational tissues in vitro. Biol Reprod 2002; 67: 668-73. http://dx.doi.org/10.1095/biolreprod67.2.668
Nishikori M. Classical and alternative NF-kB activation pathways and their roles in lymphoid malignancies. J Clin Exp Hematopathol 2005; 45: 15-24. http://dx.doi.org/10.3960/jslrt.45.15
Heng MCY. Signaling pathways targeted by curcumin in acute and chronic injury: burns and photo-damaged skin. Int J Dermatol 2012; http://dx.doi.org/10.1111/j.1365-4632.2012.05703.x
Singh S, Aggarwal BB. Activation of transcription factor NFkB is suppressed by curcumin (diferuloylmethane). J Biol Chem 1995; 270: 24995-5000. http://dx.doi.org/10.1074/jbc.270.42.24995
Araújo CAC, Leon LL. Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz 2001; 96: 723-8. http://dx.doi.org/10.1590/S0074-02762001000500026
Bharti AC, Aggarwal BB. Chemopreventive agents induce suppression of nuclear factor-kappa B leading to chemosensitization. Ann NY Acad Sci 2002; 973: 392-5. http://dx.doi.org/10.1111/j.1749-6632.2002.tb04671.x
Das L, Vinayak M. Anti-carcinogenic action of curcumin by activation of antioxidant defence system and inhibition of NF- B signalling in lymphoma-bearing mice. Biosci Rep 2012; 32: 161-70. http://dx.doi.org/10.1042/BSR20110043
Dudás J, Fullár A, Romani A, Pritz C, Kovalszky I, Schartinger VH, et al. Curcumin targets fibroblast-tumor cell interactions in oral squamous cell carcinoma. Exp Cell Res 2013; 319: 800-809. http://dx.doi.org/10.1016/j.yexcr.2012.12.001
Ali RE, Rattan SIS. Curcumin’s biphasic hormetic response on proteosome activity and heat-shock protein synthesis in human keratinocytes. Ann NY Acad Sci 2006; 1067: 394-9. http://dx.doi.org/10.1196/annals.1354.056
Kitani K, Yokozawa T, Osawa T. Interventions in aging and age-associated pathologies by means of nutritional approaches. Ann NY Acad Sci 2004; 1019: 424-6. http://dx.doi.org/10.1196/annals.1297.075
Jana NR, Dikshit P, Goswami A, Nukina N. Inhibition of proteosomal function by curcumin induces apoptosis through mitochondrial pathway. J Biol Chem 2004; 279: 11680-5. http://dx.doi.org/10.1074/jbc.M310369200
Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapyinduced apoptosis in models of human breast cancer. Cancer Res 2002; 62: 3862-75.
Nair P, Malhotra A, Dhawan DK. COX-2 as a potential target in chemoprevention of benzo(a)pyrene induced lung carcinogenesis in mice-combined role of curcumin and quercetin Am J Biomed Sci 2012; 4(3): 194-203. http://dx.doi.org/10.5099/aj120300194
Wei X, Du Z-Y, Zheng X, Cui X-X, Conney AH, Zhang K. Synthesis and evaluation of curcumin-related compounds for anticancer activity. Eur J Med Chem 2012; 53: 235-45. http://dx.doi.org/10.1016/j.ejmech.2012.04.005
Collins HM, Abdelghany MK, Messmer M, Yue B, Deeves SE, Kindle KB, et al. Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells. BMC Cancer 2013, 13: 37. http://dx.doi.org/10.1186/1471-2407-13-37
Sebastià N, Soriano JM, Barquinero JF, Villaescusa JI, Almonacid M, Cervera J, et al. In vitro cytogenetic and genotoxic effects of curcumin on human peripheral blood lymphocytes. Food Chem Toxicol 2012; 50: 3229-33. http://dx.doi.org/10.1016/j.fct.2012.06.012
