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Challenges associated with curcumin therapy in Alzheimer disease

  • Abdenour Belkacemi (a1), Sihem Doggui (a1) (a2), Lé Dao (a2) and Charles Ramassamy (a1) (a3)

Curcumin, the phytochemical agent in the spice turmeric, which gives Indian curry its yellow colour, is also a traditional Indian medicine. It has been used for millennia as a wound-healing agent and for treating a variety of ailments. The antioxidant, anti-inflammatory, antiproliferative and other properties of curcumin have only recently gained the attention of modern pharmacology. The mechanism of action of curcumin is complex and multifaceted. In part, curcumin acts by activating various cytoprotective proteins that are components of the phase II response. Over the past decade, research with curcumin has increased significantly. In vitro and in vivo studies have demonstrated that curcumin could target pathways involved in the pathophysiology of Alzheimer disease (AD), such as the β-amyloid cascade, tau phosphorylation, neuroinflammation or oxidative stress. These findings suggest that curcumin might be a promising compound for the development of AD therapy. However, its insolubility in water and poor bioavailability have limited clinical trials and its therapeutic applications. To be effective as a drug therapy, curcumin must be combined with other drugs, or new delivery strategies need to be developed.

Corresponding author
*Corresponding author: Charles Ramassamy, INRS-Institut Armand-Frappier, 531, boul. des Prairies, H7V 1B7 Laval, Québec, Canada. E-mail:
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1 H.W. Querfurth and F.M. LaFerla (2010) Alzheimer's disease. New England Journal of Medicine 362, 329-344

2 C.P. Ferri (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366, 2112-2117

3 M.A. Smith (1998) Alzheimer disease. International Review of Neurobiology 42, 1-54

4 W.A. Kukull (2002) Dementia and Alzheimer disease incidence: a prospective cohort study. Archives of Neurology 59, 1737-1746

5 J. Nunan and D.H. Small (2000) Regulation of APP cleavage by alpha-, beta- and gamma-secretases. FEBS Letters 483, 6-10

6 P.K. Panegyres (2001) The functions of the amyloid precursor protein gene. Reviews in the Neurosciences 12, 1-39

8 R.A. Black (1997) A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature 385, 729-733

9 P. Seubert (1993) Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide. Nature 361, 260-263

11 G. Evin , M.F. Sernee and C.L. Masters (2006) Inhibition of gamma-secretase as a therapeutic intervention for Alzheimer's disease: prospects, limitations and strategies. CNS Drugs 20, 351-372

12 J.A. Tschape and T. Hartmann (2006) Therapeutic perspectives in Alzheimer's disease. Recent Patients on CNS Drug Discovery 1, 119-127

13 J. Nourooz-Zadeh (1999) F4-isoprostanes as specific marker of docosahexaenoic acid peroxidation in Alzheimer's disease. Journal of Neurochemistry 72, 734-740

14 C. Ramassamy (1999) Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer's disease is related to the apolipoprotein E genotype. Free Radical Biology and Medicine 27, 544-553

15 C. Ramassamy (2000) Oxidative insults are associated with apolipoprotein E genotype in Alzheimer's disease brain. Neurobiology of Disease 7, 23-37

16 M.A. Smith (1996) Oxidative damage in Alzheimer's. Nature 382, 120-121

17 D. Pratico (2000) Increased 8,12-iso-iPF(2 alpha)-VI in Alzheimer's disease: correlation of a noninvasive index of lipid peroxidation with disease severity. Annals of Neurology 48, 809-812

19 D. Sarkar and P.B. Fisher (2006) Molecular mechanisms of aging-associated inflammation. Cancer Letters 236, 13-23

20 A. Shehzad , F. Wahid and Y.S. Lee (2010) Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Archiv der Pharmazie 343, 489-499

21 M. Singh (2008) Challenges for research on polyphenols from foods in Alzheimer's disease: bioavailability, metabolism, and cellular and molecular mechanisms. Journal of Agricultural and Food Chemistry 56, 4855-4873

22 M. Ganguli (2000) Ten-year incidence of dementia in a rural elderly US community population: the MoVIES Project. Neurology 54, 1109-1116

23 F. Kiuchi (1993) Nematocidal activity of turmeric: synergistic action of curcuminoids. Chemical and Pharmaceutical Bulletin 41, 1640-1643

24 A. Goel , A.B. Kunnumakkara and B.B. Aggarwal (2008) Curcumin as “Curecumin”: from kitchen to clinic. Biochemical Pharmacology 75, 787-809

26 A.S. Strimpakos and R.A. Sharma (2008) Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxidants and Redox Signaling 10, 511-545

27 N. Venkatesan , D. Punithavathi and V. Arumugam (2000) Curcumin prevents adriamycin nephrotoxicity in rats. British Journal of Pharmacology 129, 231-234

28 B. Joe and B.R. Lokesh (1994) Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochimica et Biophysica Acta 1224, 255-263

29 N. Sreejayan and M.N. Rao (1994) Curcuminoids as potent inhibitors of lipid peroxidation. Journal of Pharmacy and Pharmacology 46, 1013-1016.

30 M. Cekmen (2009) Curcumin prevents oxidative renal damage induced by acetaminophen in rats. Food and Chemical Toxicology 47, 1480-1484

31 F.M. El-Demerdash , M.I. Yousef and F.M. Radwan (2009) Ameliorating effect of curcumin on sodium arsenite-induced oxidative damage and lipid peroxidation in different rat organs. Food and Chemical Toxicology 47, 249-254

32 H. Farhangkhoee (2006) Differential effects of curcumin on vasoactive factors in the diabetic rat heart. Nutrition and Metabolism 3, 27

33 S. Bhaumik (1999) Curcumin mediated apoptosis in AK-5 tumor cells involves the production of reactive oxygen intermediates. FEBS Letters 456, 311-314

35 Y.Z. Cai (2006) Structure-radical scavenging activity relationships of phenolic compounds from traditional Chinese medicinal plants. Life Sciences 78, 2872-2888

36 G.K. Jayaprakasha (2006) Phenolic constituents in the fruits of Cinnamomum zeylanicum and their antioxidant activity. Journal of Agricultural and Food Chemistry 54, 1672-1679

37 W.F. Chen (2006) Curcumin and its analogues as potent inhibitors of low density lipoprotein oxidation: H-atom abstraction from the phenolic groups and possible involvement of the 4-hydroxy-3-methoxyphenyl groups. Free Radical Biology and Medicine 40, 526-535

38 P. Somparn (2007) Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biological and Pharmaceutical Bulletin 30, 74-78

39 A.A. Gorman (1994) Curcumin-derived transients: a pulsed laser and pulse radiolysis study. Photochemistry and Photobiology 59, 389-398

41 A. Dairam (2007) Curcuminoids, curcumin, and demethoxycurcumin reduce lead-induced memory deficits in male Wistar rats. Journal of Agricultural and Food Chemistry 55, 1039-1044

42 J. Ravindran (2010) Bisdemethylcurcumin and structurally related hispolon analogues of curcumin exhibit enhanced prooxidant, anti-proliferative and anti-inflammatory activities in vitro. Biochemical Pharmacology 79, 1658-1666

43 S.K. Sandur (2007) Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis 28, 1765-1773

44 U. Singh (2011) Reactions of reactive oxygen species (ROS) with curcumin analogues: structure–activity relationship. Free Radical Research 45, 317-325

45 S. Singh and B.B. Aggarwal (1995) Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. Journal of Biological Chemistry 270, 24995-25000

46 C.Y. Jin (2007) Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated BV2 microglia. Acta Pharmacologica Sinica 28, 1645-1651

49 J. Hong (2004) Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase. Carcinogenesis 25, 1671-1679

52 N. Chainani-Wu (2003) Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). Journal of Alternative and Complementary Medicine 9, 161-168

53 A.N. Begum (2008) Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. Journal of Pharmacology and Experimental Therapeutics 326, 196-208

54 M.P. Lambert (1998) Diffusible, nonfibrillar ligands derived from Abeta1–42 are potent central nervous system neurotoxins. Proceedings of the National Academy of Sciences of the United States of America 95, 6448-6453

56 M. Necula (2007) Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct. Journal of Biological Chemistry 282, 10311-10324

57 H. Kim (2005) Effects of naturally occurring compounds on fibril formation and oxidative stress of beta-amyloid. Journal of Agricultural and Food Chemistry 53, 8537-8541

58 K. Ono (2004) Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. Journal of Neuroscience Research 75, 742-750

60 C. Zhang (2010) Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein. Journal of Biological Chemistry 285, 28472-28480

61 M. Garcia-Alloza (2007) Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. Journal of Neurochemistry 102, 1095-1104

62 M. Demeule (2002) Drug transport to the brain: key roles for the efflux pump P-glycoprotein in the blood–brain barrier. Vascular Pharmacology 38, 339-348

63 N. Romiti (1998) Effects of curcumin on P-glycoprotein in primary cultures of rat hepatocytes. Life Sciences 62, 2349-2358

64 F. Yang (2005) Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. Journal of Biological Chemistry 280, 5892-5901

66 S.A. Frautschy (2001) Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiology of Aging 22, 993-1005

67 M.J. Ansari (2005) Stability-indicating HPTLC determination of curcumin in bulk drug and pharmaceutical formulations. Journal of Pharmaceutical and Biomedical Analysis 39, 132-138

68 Y.J. Wang (1997) Stability of curcumin in buffer solutions and characterization of its degradation products. Journal of Pharmaceutical and Biomedical Analysis 15, 1867-1876

70 B. Wahlang , Y.B. Pawar and A.K. Bansal (2011) Identification of permeability-related hurdles in oral delivery of curcumin using the Caco-2 cell model. European Journal of Pharmaceutics and Biopharmaceutics 77, 275-282

73 S.K. Vareed (2008) Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiology, Biomarkers and Prevention 17, 1411-1417

75 P. Murugan and L. Pari (2006) Effect of tetrahydrocurcumin on lipid peroxidation and lipids in streptozotocin-nicotinamide-induced diabetic rats. Basic and Clinical Pharmacology and Toxicology 99, 122-127

76 P. Murugan and L. Pari (2006) Antioxidant effect of tetrahydrocurcumin in streptozotocin-nicotinamide induced diabetic rats. Life Sciences 79, 1720-1728

77 S.O. Jeong (2009) Dimethoxycurcumin, a synthetic curcumin analogue, induces heme oxygenase-1 expression through Nrf2 activation in RAW264.7 macrophages. Journal of Clinical Biochemistry and Nutrition 44, 79-84

78 G. Shoba (1998) Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Medica 64, 353-356

79 S. Manju and K. Sreenivasan (2011) Synthesis and characterization of a cytotoxic cationic polyvinylpyrrolidone-curcumin conjugate. Journal of Pharmaceutical Sciences 100, 504-511

80 N.K. Gupta and V.K. Dixit (2011) Bioavailability enhancement of curcumin by complexation with phosphatidyl choline. Journal of Pharmaceutical Sciences 100, 1987-1995

81 S. Setthacheewakul (2010) Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats. European Journal of Pharmaceutics and Biopharmaceutics 76, 475-485

82 M. Takahashi (2009) Evaluation of an oral carrier system in rats: bioavailability and antioxidant properties of liposome-encapsulated curcumin. Journal of Agricultural and Food Chemistry 57, 9141-9146

84 P. Anand (2007) Bioavailability of curcumin: problems and promises. Molecular Pharmaceutics 4, 807-818

85 J. Shaikh (2009) 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 37, 223-230

86 H.H. Tonnesen , M. Masson and T. Loftsson (2002) Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stability. International Journal of Pharmaceutics 244, 127-135

87 M.M. Yallapu (2010) Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells. Journal of Colloid and Interface Science 351, 19-29

89 C. Mohanty and S.K. Sahoo (2010) The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation. Biomaterials 31, 6597-6611

90 S. Bisht (2007) Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): a novel strategy for human cancer therapy. Journal of Nanobiotechnology 5, 3

91 J. Cui (2009) Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems. International Journal of Pharmaceutics 371, 148-155

93 A. Sahu (2008) Synthesis of novel biodegradable and self-assembling methoxy poly(ethylene glycol)-palmitate nanocarrier for curcumin delivery to cancer cells. Acta Biomaterialia 4, 1752-1761

94 P. Anand (2010) Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. Biochemical Pharmacology 79, 330-338

96 J. Duan (2010) Synthesis and in vitro/in vivo anti-cancer evaluation of curcumin-loaded chitosan/poly(butyl cyanoacrylate) nanoparticles. International Journal of Pharmaceutics 400, 211-220

97 A. Sahu , N. Kasoju and U. Bora (2008) Fluorescence study of the curcumin-casein micelle complexation and its application as a drug nanocarrier to cancer cells. Biomacromolecules 9, 2905-2912

98 Z. Song (2011) Curcumin-loaded PLGA-PEG-PLGA triblock copolymeric micelles: preparation, pharmacokinetics and distribution in vivo. Journal of Colloid and Interface Science 354, 116-123

99 M. Sun (2010) Enhancement of transport of curcumin to brain in mice by poly(n-butylcyanoacrylate) nanoparticle. Journal of Nanoparticle Research 12, 3111-3122

100 C.L. Martel (1997) Isoform-specific effects of apolipoproteins E2, E3, and E4 on cerebral capillary sequestration and blood–brain barrier transport of circulating Alzheimer's amyloid beta. Journal of Neurochemistry 69, 1995-2004

102 P. Khumsupan (2011) Apolipoprotein E LDL receptor-binding domain-containing high-density lipoprotein: a nanovehicle to transport curcumin, an antioxidant and anti-amyloid bioflavonoid. Biochimica et Biophysica Acta 1808, 352-359

103 R.S. Mulik (2010) ApoE3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin: study of enhanced activity of curcumin against beta amyloid induced cytotoxicity using in vitro cell culture model. Molecular Pharmaceutics 7, 815-825

105 J. Panyam and V. Labhasetwar (2003) Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Advanced Drug Delivery Reviews 55, 329-347

106 Y.L. Hu and J.Q. Gao (2010) Potential neurotoxicity of nanoparticles. International Journal of Pharmaceutics 394, 115-121

107 W.H. Wu (2008) TiO2 nanoparticles promote beta-amyloid fibrillation in vitro. Biochemical and Biophysical Research Communications 373, 315-318

108 R. Hu (2010) Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to TiO2 nanoparticles. Biomaterials 31, 8043-8050

109 L. Baum (2008) Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. Journal of Clinical Psychopharmacology 28, 110-113

110 J.M. Ringman (2008) Biochemical markers in persons with preclinical familial Alzheimer disease. Neurology 71, 85-92

111 V. Ravindranath and N. Chandrasekhara (1980) Absorption and tissue distribution of curcumin in rats. Toxicology 16, 259-265

113 V. Kakkar (2011) Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin. Molecular Nutrition and Food Research 55, 495-503

A.P. Kulkarni (2011) Modulation of anxiety behavior by intranasally administered vaccinia virus complement control protein and curcumin in a mouse model of Alzheimer's disease. Current Alzheimer Research 8, 95-113

N. Mohorko (2010) Curcumin labeling of neuronal fibrillar tau inclusions in human brain samples. Journal of Neuropathology and Experimental Neurology 69, 405-414

K.H. Reeta (2011) Pharmacokinetic and pharmacodynamic interactions of valproate, phenytoin, phenobarbitone and carbamazepine with curcumin in experimental models of epilepsy in rats. Pharmacology, Biochemistry and Behavior 99, 399-407

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