Advertisement

Neurological Sciences

, Volume 39, Issue 2, pp 207–214 | Cite as

Therapeutic potential of curcumin for multiple sclerosis

  • Munibah Qureshi
  • Ebtesam A. Al-Suhaimi
  • Fazli Wahid
  • Omer Shehzad
  • Adeeb ShehzadEmail author
Review Article

Abstract

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS), characterized by demyelination, neuronal injury, and breaching of the blood-brain barrier (BBB). Epidemiological studies have shown that immunological, genetic, and environmental factors contribute to the progression and development of MS. T helper 17 (Th17) cells are crucial immunological participant in the pathophysiology of MS. The aberrant production of IL-17 and IL-22 by Th17 cells crosses BBB promotes its disruption and interferes with transmission of nerve signals through activation of neuroinflammation in the CNS. These inflammatory responses promote demyelination through transcriptional activation of signal transducers and activators of transcription-1 (STAT-1), nuclear factor kappa-B (NF-κB), matrix metalloproteinases (MMPs), interferon ϒ (IFNϒ), and Src homology region 2 domain-containing phosphatase-1 (SHP-1). B cells also contribute to disease progression through abnormal regulation of antibodies, cytokines, and antigen presentation. Additionally, oxidative stress has been known as a causative agent for the MS. Curcumin is a hydrophobic yellowish diphenolic component of turmeric, which can interact and modulate multiple cell signaling pathways and prevent the development of various autoimmune neurological diseases including MS. Studies have reported curcumin as a potent anti-inflammatory, antioxidant agent that could modulate cell cycle regulatory proteins, enzymes, cytokines, and transcription factors in CNS-related disorders including MS. The current study summarizes the reported knowledge on therapeutic potential of curcumin against MS, with future indication as neuroprotective and neuropharmacological drug.

Keywords

Curcumin Multiple sclerosis Autoimmunediseases Th-17cells B cells Oxidative stress 

Notes

Compliance with ethical standards

Competing interests

The authors declare that they have no conflict of interest.

References

  1. 1.
    Haider L, Zrzavy T, Hametner S et al (2016) The topograpy of demyelination and neurodegeneration in the multiple sclerosis. Brain 139:807–815.  https://doi.org/10.1093/brain/awv398 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Browne P, Chandraratna D, Angood C et al (2014) Atlas of multiple sclerosis 2013: a growing global problem with widespread inequity. Neurology 83:1022–1024.  https://doi.org/10.1212/WNL.0000000000000768 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Jadidi-Niaragh F, Mirshafiey A (2011) Th17 cell, the new player of neuroinflammatory process in multiple sclerosis. Scand J Immunol 74:1–13.  https://doi.org/10.1111/j.1365-3083.2011.02536.x CrossRefPubMedGoogle Scholar
  4. 4.
    Jäger A, Dardalhon V, R a S et al (2009) Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol 183:7169–7177.  https://doi.org/10.4049/jimmunol.0901906 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Elyaman W, Bradshaw EM, Uyttenhove C et al (2009) IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci U S A 106:12885–12890.  https://doi.org/10.1073/pnas.0812530106 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Wekerle H (2017) B cells in multiple sclerosis. Autoimmunity 50:57–60.  https://doi.org/10.1080/08916934.2017.1281914 CrossRefPubMedGoogle Scholar
  7. 7.
    Von Geldern G, Mowry EM (2012) The influence of nutritional factors on the prognosis of multiple sclerosis. Nat Rev Neurol 8:678–689.  https://doi.org/10.1038/nrneurol.2012.194 CrossRefGoogle Scholar
  8. 8.
    Iwu, Maurice M (2014) Handbook of African medcinal plantsGoogle Scholar
  9. 9.
    Costa SL, Silva VDA, dos Santos Souza C et al (2016) Impact of plant-derived flavonoids on neurodegenerative diseases. Neurotox Res 30:41–52.  https://doi.org/10.1007/s12640-016-9600-1 CrossRefPubMedGoogle Scholar
  10. 10.
    Ginwala R, McTish E, Raman C et al (2016) Apigenin, a natural flavonoid, attenuates EAE severity through the modulation of dendritic cell and other immune cell functions. J NeuroImmune Pharmacol 11:36–47.  https://doi.org/10.1007/s11481-015-9617-x CrossRefPubMedGoogle Scholar
  11. 11.
    Zhang Y, Li X, Ciric B et al (2015) Therapeutic effect of baicalin on experimental autoimmune encephalomyelitis is mediated by SOCS3 regulatory pathway. Sci Rep 5:17407.  https://doi.org/10.1038/srep17407 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ghaiad HR, Nooh MM, El-Sawalhi MM, Shaheen A a (2016) Resveratrol promotes remyelination in cuprizone model of multiple sclerosis: biochemical and histological study. Mol Neurobiol 1–11.  https://doi.org/10.1007/s12035-016-9891-5
  13. 13.
    Mrvová N, Škandík M, Kuniaková M, Račková L (2015) Modulation of BV-2 microglia functions by novel quercetin pivaloyl ester. Neurochem Int 90:246–254.  https://doi.org/10.1016/j.neuint.2015.09.005 CrossRefPubMedGoogle Scholar
  14. 14.
    Barbierato M, Facci L, Marinelli C et al (2015) Co-ultramicronized palmitoylethanolamide/luteolin promotes the maturation of oligodendrocyte precursor cells. Sci Rep 5:16676.  https://doi.org/10.1038/srep16676 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zhang K, Ge Z, Xue Z et al (2015) Chrysin suppresses human CD14+ monocyte-derived dendritic cells and ameliorates experimental autoimmune encephalomyelitis. J Neuroimmunol 288:13–20.  https://doi.org/10.1016/j.jneuroim.2015.08.017 CrossRefPubMedGoogle Scholar
  16. 16.
    Wang WW, Lu L, Bao TH et al (2016) Scutellarin alleviates behavioral deficits in a mouse model of multiple sclerosis, possibly through protecting neural stem cells. J Mol Neurosci 58:210–220.  https://doi.org/10.1007/s12031-015-0660-0 CrossRefPubMedGoogle Scholar
  17. 17.
    Ciftci O, Ozcan C, Kamisli O, Nese C (2015) Hesperidin, a citrus flavonoid, has the ameliorative effects against experimental autoimmune encephalomyelitis (EAE) in a C57BL / J6 mouse model. Neurochem Res 40:1111–1120.  https://doi.org/10.1007/s11064-015-1571-8 CrossRefPubMedGoogle Scholar
  18. 18.
    Shen R, Deng W, Li C, Zeng G (2015) A natural flavonoid glucoside icariin inhibits Th1 and Th17 cell differentiation and ameliorates experimental autoimmune encephalomyelitis. Int Immunopharmacol 24:224–231.  https://doi.org/10.1016/j.intimp.2014.12.015 CrossRefPubMedGoogle Scholar
  19. 19.
    Seyedzadeh MH, Safari Z, Zare A et al (2014) Study of curcumin immunomodulatory effects on reactive astrocyte cell function. Int Immunopharmacol 22:230–235.  https://doi.org/10.1016/j.intimp.2014.06.035 CrossRefPubMedGoogle Scholar
  20. 20.
    Cheng KK, Yeung CF, Ho SW et al (2013) Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer’s disease Tg2576 mice. AAPS J 15:324–336.  https://doi.org/10.1208/s12248-012-9444-4 CrossRefPubMedGoogle Scholar
  21. 21.
    Monroy A, Lithgow GJ, Alavez S (2013) Curcumin and neurodegenerative diseases. Biofactors 39:122–132.  https://doi.org/10.1002/biof.1063 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Calabrese M, Magliozzi R, Ciccarelli O et al (2015) Exploring the origins of grey matter damage in multiple sclerosis. Nat Rev Neurosci 16:147–158.  https://doi.org/10.1038/nrn3900 CrossRefPubMedGoogle Scholar
  23. 23.
    Tavazzi E, Laganà MM, Bergsland N et al (2014) Grey matter damage in progressive multiple sclerosis versus amyotrophic lateral sclerosis: a voxel-based morphometry MRI study. Neurol Sci 36:371–377.  https://doi.org/10.1007/s10072-014-1954-7 CrossRefPubMedGoogle Scholar
  24. 24.
    Incerti CC, Argento O, Magistrale G et al (2016) Adverse working events in patients with multiple sclerosis. Neurol Sci 38:1–4.  https://doi.org/10.1007/s10072-016-2737-0 Google Scholar
  25. 25.
    Kutzelnigg A, Lassmann H (2014) Pathology of multiple sclerosis and related inflammatory demyelinating diseases, 1st ed. Handb Clin Neurol.  https://doi.org/10.1016/B978-0-444-52001-2.00002-9
  26. 26.
    KG S, Banker G, Bourdette D, Forte M (2009) Axonal degeneration in multiple sclerosis: the mitochondrial hypothesis. Curr Neurol Neurosci Rep 9:411–417.  https://doi.org/10.1007/s11910-009-0060-3 CrossRefGoogle Scholar
  27. 27.
    Ingram G, Loveless S, Howell OW et al (2014) Complement activation in multiple sclerosis plaques: an immunohistochemical analysis. Acta Neuropathol Commun 2:53.  https://doi.org/10.1186/2051-5960-2-53 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Mirshafiey A, Asghari B, Ghalamfarsa G et al (2014) The significance of matrix metalloproteinases in the immunopathogenesis and treatment of multiple sclerosis. Sultan Qaboos Univ Med J 14:13–25CrossRefGoogle Scholar
  29. 29.
    Gilgun-Sherki Y, Melamed E, Offen D (2004) The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol 251:261–268.  https://doi.org/10.1007/s00415-004-0348-9 CrossRefPubMedGoogle Scholar
  30. 30.
    Christophi GP, Panos M, C a H et al (2009) Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype. Lab Investig 89:742–759.  https://doi.org/10.1038/labinvest.2009.32 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kolls JK, Linde A (2004) Interleukin-17 family members. Immunity 21:467–476.  https://doi.org/10.1016/j.immuni.2004.08.018 CrossRefPubMedGoogle Scholar
  32. 32.
    Miljkovic D, Cvetkovic I, Momcilovic M et al (2005) Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells. Cell Mol Life Sci 62:2658–2668.  https://doi.org/10.1007/s00018-005-5259-0 CrossRefPubMedGoogle Scholar
  33. 33.
    Li J, Gran B, Zhang GX et al (2003) Differential expression and regulation of IL-23 and IL-12 subunits and receptors in adult mouse microglia. J Neurol Sci 215:95–103.  https://doi.org/10.1016/S0022-510X(03)00203-X CrossRefPubMedGoogle Scholar
  34. 34.
    Anagnostouli M, Christidi F, Zalonis I et al (2015) Clinical and cognitive implications of cerebrospinal fluid oligoclonal bands in multiple sclerosis patients. Neurol Sci 36:2053–2060.  https://doi.org/10.1007/s10072-015-2303-1 CrossRefPubMedGoogle Scholar
  35. 35.
    Hao J, Liu R, Piao W et al (2010) Central nervous system (CNS)-resident natural killer cells suppress Th17 responses and CNS autoimmune pathology. J Exp Med 207:1907–1921.  https://doi.org/10.1084/jem.20092749 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Liu Q, Sanai N, Jin W-N, et al (2016) Neural stem cells sustain natural killer cells that dictate recovery from brain inflammation. Nat Neurosci 1–12.  https://doi.org/10.1038/nn.4211
  37. 37.
    Ortiz GG, Pacheco-mois P, Angel M et al (2014) Role of the blood e brain barrier in multiple sclerosis. Arch Med Res.  https://doi.org/10.1016/j.arcmed.2014.11.013
  38. 38.
    Kebir H, Kreymborg K, Ifergan I et al (2007) Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 13:1173–1175.  https://doi.org/10.1038/nm1651 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Huppert J, Closhen D, Croxford A et al Cellular mechanisms of IL-17-induced blood-brain barrier disruption. FASEB J.  https://doi.org/10.1096/fj.09-141978
  40. 40.
    Priyadarsini KI (2014) The chemistry of curcumin: from extraction to therapeutic agent. Molecules 19:20091–20112.  https://doi.org/10.3390/molecules191220091 CrossRefPubMedGoogle Scholar
  41. 41.
    Federico A, Cardaioli E, Da Pozzo P et al (2012) Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 322:254–262.  https://doi.org/10.1016/j.jns.2012.05.030 CrossRefPubMedGoogle Scholar
  42. 42.
    Follett J, Bugarcic A, Yang Z et al (2016) Parkinson’s disease linked Vps35 R524W mutation impairs the endosomal association of retromer and induces α -synuclein aggregation. J Biol Chem 291:18283–18298.  https://doi.org/10.1074/jbc.M115.703157 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Palmqvist S, Mattsson N, Hansson O (2016) Cerebrospinal fluid analysis detects cerebral amyloid-ß accumulation earlier than positron emission tomography. Brain 139:1226–1236.  https://doi.org/10.1093/brain/aww015 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Bates G (2003) Huntingtin aggregation and toxicity in Huntington’s disease. Lancet 361:1642–1644.  https://doi.org/10.1016/S0140-6736(03)13304-1 CrossRefPubMedGoogle Scholar
  45. 45.
    Farina M, Avila DS, Da Rocha JBT, Aschner M (2013) Metals, oxidative stress and neurodegeneration: a focus on iron, manganese and mercury. Neurochem Int 62:575–594.  https://doi.org/10.1016/j.neuint.2012.12.006 CrossRefPubMedGoogle Scholar
  46. 46.
    Chin-Chan M, Navarro-Yepes J, Quintanilla-Vega B (2015) Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front Cell Neurosci 9:124.  https://doi.org/10.3389/fncel.2015.00124 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Fischer R, Maier O (2015) Interrelation of oxidative stress and inflammation in neurodegenerative disease: role of TNF. Oxidative Med Cell Longev 2015:1–18CrossRefGoogle Scholar
  48. 48.
    Zhou H, Beevers CS, Huang S (2011) The targets of curcumin. Curr Drug Targets 12:332–347CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Chen J-J, Dai L, Zhao L-X et al (2015) Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis. Sci Rep 5:10278.  https://doi.org/10.1038/srep10278 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Ma QL, Zuo X, Yang F et al (2013) Curcumin suppresses soluble Tau dinners and corrects molecular chaperone, synaptic, and behavioral deficits in aged human Tau transgenic mice. J Biol Chem 288:4056–4065.  https://doi.org/10.1074/jbc.M112.393751 CrossRefPubMedGoogle Scholar
  51. 51.
    Farooqui, A A (2016) Therapeutic potentials of curcumin for Alzheimer disease.  https://doi.org/10.1007/978–3–319-15889-1
  52. 52.
    Ji H-F, Shen L (2014) The multiple pharmaceutical potential of curcumin in Parkinson’s disease. CNS Neurol Disord Drug Targets 13:369–373.  https://doi.org/10.2174/18715273113129990077 CrossRefPubMedGoogle Scholar
  53. 53.
    Chongtham A, Agrawal N (2016) Curcumin modulates cell death and is protective in Huntington’s disease model. Sci Rep 6:18736.  https://doi.org/10.1038/srep18736 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Wu A, Noble EE, Tyagi E et al (2015) Curcumin boosts DHA in the brain: implications for the prevention of anxiety disorders. BBA Mol Basis Dis 1852:951–961.  https://doi.org/10.1016/j.bbadis.2014.12.005 CrossRefGoogle Scholar
  55. 55.
    Xie L, Li XK, Funeshima-Fuji N et al (2009) Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production. Int Immunopharmacol 9:575–581.  https://doi.org/10.1016/j.intimp.2009.01.025 CrossRefPubMedGoogle Scholar
  56. 56.
    Yu HJ, Lan Ma JJ, SQS (2016) Protective effect of curcumin on neural myelin sheaths by attenuating interactions between the endoplasmic reticulum and mitochondria after compressed spinal cord. J Spine 5:2.  https://doi.org/10.4172/2165-7939.1000322 Google Scholar
  57. 57.
    Kim G-Y, Kim K-H, Lee S-H et al (2005) Curcumin inhibits Immunostimulatory function of dendritic cells: MAPKs and translocation of NF- B as potential targets. J Immunol 174:8116–8124.  https://doi.org/10.4049/jimmunol.174.12.8116 CrossRefPubMedGoogle Scholar
  58. 58.
    Orrenius S, Gogvadze V, Zhivotovsky B (2007) Mitochondrial oxidative stress: implications for cell death. Annu Rev Pharmacol Toxicol 47:143–183.  https://doi.org/10.1146/annurev.pharmtox.47.120505.105122 CrossRefPubMedGoogle Scholar
  59. 59.
    Chearwae W, Bright JJ (2008) 15-Deoxy- Δ 12, 14 -prostaglandin J 2 and curcumin modulate the expression of toll-like receptors 4 and 9 in autoimmune T lymphocyte. J Clin Immunol 28:558–570.  https://doi.org/10.1007/s10875-008-9202-7 CrossRefPubMedGoogle Scholar
  60. 60.
    Natarajan C, Bright JJ (2002) Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes. J Immunol 168:6506–6513.  https://doi.org/10.4049/jimmunol.168.12.6506 CrossRefPubMedGoogle Scholar
  61. 61.
    Kanakasabai S, Casalini E, Walline CC et al (2012) Differential regulation of CD4 + T helper cell responses by curcumin in experimental autoimmune encephalomyelitis. J Nutr Biochem 23:1498–1507.  https://doi.org/10.1016/j.jnutbio.2011.10.002 CrossRefPubMedGoogle Scholar
  62. 62.
    Feng J, Tao T, Yan W et al (2014) Curcumin inhibits mitochondrial injury and apoptosis from the early stage in EAE mice. Oxidative Med Cell Longev 2014:1–11.  https://doi.org/10.1155/2014/728751 CrossRefGoogle Scholar
  63. 63.
    Abbott NJ (2002) Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 200:629–638.  https://doi.org/10.1046/j.1469-7580.2002.00064.x CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Jin CY, Lee JD, Park C et al (2007) Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated BV2 microglia. Acta Pharmacol Sin 28:1645–1651.  https://doi.org/10.1111/j.1745-7254.2007.00651.x CrossRefPubMedGoogle Scholar
  65. 65.
    Agrawal SM, Lau L, Yong VW (2008) MMPs in the central nervous system: where the good guys go bad. Sem Cell Dev Biol 19:42–51.  https://doi.org/10.1016/j.semcdb.2007.06.003 CrossRefGoogle Scholar
  66. 66.
    Zhang ZJ, Zhao LX, Cao DL et al (2012) Curcumin inhibits LPS-induced CCL2 expression via JNK pathway in C6 rat astrocytoma cells. Cell Mol Neurobiol 32:1003–1010.  https://doi.org/10.1007/s10571-012-9816-4 CrossRefPubMedGoogle Scholar
  67. 67.
    Kimura K, Teranishi S, Fukuda K et al (2008) Delayed disruption of barrier function in cultured human corneal epithelial cells induced by tumor necrosis factor-alpha in a manner dependent on NF-kappaB. Invest Ophthalmol Vis Sci 49:565–571.  https://doi.org/10.1167/iovs.07-0419 CrossRefPubMedGoogle Scholar
  68. 68.
    Carlson T, Kroenke M, Rao P et al (2008) The Th17-ELR+ CXC chemokine pathway is essential for the development of central nervous system autoimmune disease. J Exp Med 205:811–823.  https://doi.org/10.1084/jem.20072404 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Bachmeier BE, Mohrenz IV, Mirisola V et al (2008) Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFκB. Carcinogenesis 29:779–789.  https://doi.org/10.1093/carcin/bgm248 CrossRefPubMedGoogle Scholar
  70. 70.
    Kamohara H, Takahashi M, Ishiko T et al (2007) Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-alpha and leukemia inhibitory factor in pancreatic carcinoma cells: impact of CXCL-8 as an autocrine growth factor. Int J Oncol 31:627–632PubMedGoogle Scholar
  71. 71.
    Choi KH, Park JW, Kim HY et al (2010) Cellular factors involved in CXCL8 expression induced by glycated serum albumin in vascular smooth muscle cells. Atherosclerosis 209:58–65.  https://doi.org/10.1016/j.atherosclerosis.2009.08.030 CrossRefPubMedGoogle Scholar
  72. 72.
    Liu H, Yang J, Li L et al (2016) The natural occurring compounds targeting endoplasmic reticulum stress. J Evid Based Complementary Altern Med 1113:58–71.  https://doi.org/10.1196/annals.1391.007 Google Scholar
  73. 73.
    Zheng M, Zhang Q, Joe Y et al (2013) Curcumin induces apoptotic cell death of activated human CD4 + T cells via increasing endoplasmic reticulum stress and mitochondrial dysfunction. Int Immunopharmacol 15:517–523.  https://doi.org/10.1016/j.intimp.2013.02.002 CrossRefPubMedGoogle Scholar
  74. 74.
    Tegenge MA, Rajbhandari L, Shrestha S et al (2014) Curcumin protects axons from degeneration in the setting of local neuroinflammation. Exp Neurol 253:102–110.  https://doi.org/10.1016/j.expneurol.2013.12.016 CrossRefPubMedGoogle Scholar
  75. 75.
    Baker M (2016) Chemists warn against deceptive molecules: spice extract curcumin dupes assays and leads some drug hunters astray. Nature 541:144–145CrossRefGoogle Scholar
  76. 76.
    Nelson KM, Dahlin JL, Bisson J et al (2017) The essential medicinal chemistry of curcumin. J Med Chem 60:1620.  https://doi.org/10.1021/acs.jmedchem.6b00975 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Series AC (2008) Letters to the editors suicidal ideation associated with duloxetine use successful treatment of nicotine withdrawal with duloxetine a case report. J Clin Pharmacol 28:101–122Google Scholar
  78. 78.
    Ringman JM, S a F, Teng E et al (2012) Oral curcumin for Alzheimer’s disease: tolerability and efficacy in a 24-week randomized, double-blind, placebo-controlled study. Alzheimers Res Ther 4:43.  https://doi.org/10.1186/alzrt146 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l. 2017

Authors and Affiliations

  1. 1.Department of Biomedical Engineering and Sciences, School of Mechanical and Manufacturing EngineeringNational University of Sciences and TechnologyIslamabadPakistan
  2. 2.Department of Biology, Sciences CollegeUniversity of DammamDammamSaudi Arabia
  3. 3.Biotechnology Program, Department of Environmental SciencesCOMSATS Institute of Information TechnologyAbbottabadPakistan
  4. 4.Department of pharmacyAbdul Wali Khan University MardanPakistan

Personalised recommendations