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Neurotoxicity Research

, Volume 36, Issue 1, pp 12–26 | Cite as

Effects of Curcumin on Microglial Cells

  • Faezeh Ghasemi
  • Hossein Bagheri
  • George E. Barreto
  • Morgayn I. Read
  • Amirhossein SahebkarEmail author
Review

Abstract

Microglia are innate immune system cells which reside in the central nervous system (CNS). Resting microglia regulate the homeostasis of the CNS via phagocytic activity to clear pathogens and cell debris. Sometimes, however, to protect neurons and fight invading pathogens, resting microglia transform to an activated-form, producing inflammatory mediators, such as cytokines, chemokines, iNOS/NO and cyclooxygenase-2 (COX-2). Excessive inflammation, however, leads to damaged neurons and neurodegenerative diseases (NDs), such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Curcumin is a phytochemical isolated from Curcuma longa. It is widely used in Asia and has many therapeutic properties, including antioxidant, anti-viral, anti-bacterial, anti-mutagenic, anti-amyloidogenic and anti-inflammatory, especially with respect to neuroinflammation and neurological disorders (NDs). Curcumin is a pleiotropic molecule that inhibits microglia transformation, inflammatory mediators and subsequent NDs. In this mini-review, we discuss the effects of curcumin on microglia and explore the underlying mechanisms.

Keywords

Curcumin Microglia, neuroinflammation Neuroprotection Neurodegenerative diseases 

Notes

Authors’ Contributions

Conceived and design: FG, HB, GEB, AEB, AS

Wrote the manuscript: HB, FG, GEB, AS, AEB

All authors have approved final manuscript and submission.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Abdollahi E, Momtazi AA, Johnston TP, Sahebkar A (2018) Therapeutic effects of curcumin in inflammatory and immune-mediated diseases: a nature-made jack-of-all-trades? J Cell Physiol 233:830–848.  https://doi.org/10.1002/jcp.25778 Google Scholar
  2. Agrawal DK, Mishra PK (2010) Curcumin and its analogues: potential anticancer agents. Med Res Rev 30:818–860Google Scholar
  3. Akaishi T, Abe K (2018) CNB-001, a synthetic pyrazole derivative of curcumin, suppresses lipopolysaccharide-induced nitric oxide production through the inhibition of NF-kappaB and p38 MAPK pathways in microglia. Eur J Pharmacol 819:190–197.  https://doi.org/10.1016/j.ejphar.2017.12.008 Google Scholar
  4. Alexiou A, Soursou G, Chatzichronis S, Gasparatos E, Kamal MA, Yarla NS, Perveen A, Barreto GE, Ashraf GM (2018) Role of GTPases in the regulation of mitochondrial dynamics in Alzheimer’s disease and CNS-related disorders. Mol Neurobiol.  https://doi.org/10.1007/s12035-018-1397-x
  5. Alliot F, Godin I, Pessac B (1999) Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res 117:145–152Google Scholar
  6. Ameruoso A, Palomba R, Palange AL, Cervadoro A, Lee A, di Mascolo D, Decuzzi P (2017) Ameliorating amyloid-beta fibrils triggered inflammation via curcumin-loaded polymeric nanoconstructs. Front Immunol 8:1411.  https://doi.org/10.3389/fimmu.2017.01411 Google Scholar
  7. Avan A, Shahidsales S, Bahmani Z, Ghasemi F, Hassanian SM, Sahebkar A (2016) 19P curcumin oleoresin inhibits cell growth and migratory properties of breast cancer cells through inhibition of NF-kB pathway. Ann Oncol 27:mdw573.018-mdw573.018.  https://doi.org/10.1093/annonc/mdw573.018 Google Scholar
  8. Bavarsad K, Barreto GE, Hadjzadeh MA, Sahebkar A (2018) Protective effects of curcumin against ischemia-reperfusion injury in the nervous system. Mol Neurobiol 56:1391–1404.  https://doi.org/10.1007/s12035-018-1169-7 Google Scholar
  9. Bennett ML, Bennett FC, Liddelow SA, Ajami B, Zamanian JL, Fernhoff NB, Mulinyawe SB, Bohlen CJ, Adil A, Tucker A, Weissman IL, Chang EF, Li G, Grant GA, Hayden Gephart MG, Barres BA (2016) New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci U S A 113:E1738–E1746.  https://doi.org/10.1073/pnas.1525528113 Google Scholar
  10. Bhattacharjee S, Zhao Y, Dua P, Rogaev EI, Lukiw WJ (2016) microRNA-34a-mediated down-regulation of the microglial-enriched triggering receptor and phagocytosis-sensor TREM2 in age-related macular degeneration. PLoS One 11:e0150211.  https://doi.org/10.1371/journal.pone.0150211 Google Scholar
  11. Bianconi V, Mannarino MR, Sahebkar A, Cosentino T, Pirro M (2018) Cholesterol-lowering nutraceuticals affecting vascular function and cardiovascular disease risk. Curr Cardiol Rep 20:53.  https://doi.org/10.1007/s11886-018-0994-7 Google Scholar
  12. Cabezas R, El-Bacha RS, Gonzalez J, Barreto GE (2012) Mitochondrial functions in astrocytes: neuroprotective implications from oxidative damage by rotenone. Neurosci Res 74:80–90.  https://doi.org/10.1016/j.neures.2012.07.008 Google Scholar
  13. Cabezas R, Baez-Jurado E, Hidalgo-Lanussa O, Echeverria V, Ashrad GM, Sahebkar A, Barreto GE (2018) Growth factors and neuroglobin in astrocyte protection against neurodegeneration and oxidative stress. Mol Neurobiol.  https://doi.org/10.1007/s12035-018-1203-9
  14. Canales-Aguirre AA, Gomez-Pinedo UA, Luquin S, Ramirez-Herrera MA, Mendoza-Magana ML et al (2012) Curcumin protects against the oxidative damage induced by the pesticide parathion in the hippocampus of the rat brain. Nutr Neurosci 15:62–69.  https://doi.org/10.1179/1476830511Y.0000000034 Google Scholar
  15. Chen G, Liu S, Pan R, Li G, Tang H, Jiang M, Xing Y, Jin F, Lin L, Dong J (2018a) Curcumin attenuates gp120-induced microglial inflammation by inhibiting autophagy via the PI3K pathway. Cell Mol Neurobiol 38:1465–1477.  https://doi.org/10.1007/s10571-018-0616-3 Google Scholar
  16. Chen H, Tang Y, Wang H, Chen W, Jiang H (2018b) Curcumin alleviates lipopolysaccharide-induced neuroinflammation in fetal mouse brain. Restor Neurol Neurosci 36:583–592.  https://doi.org/10.3233/RNN-180834 Google Scholar
  17. Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF et al (2001) Phase I clinical trial of curcumin, 488 a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21:2895–2900Google Scholar
  18. Chiu SS, Lui E, Majeed M, Vishwanatha JK, Ranjan AP, Maitra A, Pramanik D,Smith JA, Helson L (2011) Differential distribution of intravenous curcuminformulations in the rat brain. Anticancer Res. Mar;31(3):907–11Google Scholar
  19. Choi DK, Koppula S, Suk K (2011) Inhibitors of microglial neurotoxicity: focus on natural products. Molecules 16:1021–1043.  https://doi.org/10.3390/molecules16021021 Google Scholar
  20. Cianciulli A, Calvello R, Porro C, Trotta T, Salvatore R, Panaro MA (2016) PI3k/Akt signalling pathway plays a crucial role in the anti-inflammatory effects of curcumin in LPS-activated microglia. Int Immunopharmacol 36:282–290.  https://doi.org/10.1016/j.intimp.2016.05.007 Google Scholar
  21. Cicero AFG, Colletti A, Bajraktari G, Descamps O, Djuric DM, Ezhov M, Fras Z, Katsiki N, Langlois M, Latkovskis G, Panagiotakos DB, Paragh G, Mikhailidis DP, Mitchenko O, Paulweber B, Pella D, Pitsavos C, Reiner Ž, Ray KK, Rizzo M, Sahebkar A, Serban MC, Sperling LS, Toth PP, Vinereanu D, Vrablík M, Wong ND, Banach M (2017) Lipid lowering nutraceuticals in clinical practice: position paper from an international lipid. Expert Panel Arch Med Sci 13:965–1005.  https://doi.org/10.5114/aoms.2017.69326 Google Scholar
  22. Colonna M, Butovsky O (2017) Microglia function in the central nervous system during health and neurodegeneration. Annu Rev Immunol 35:441–468.  https://doi.org/10.1146/annurev-immunol-051116-052358 Google Scholar
  23. Deguine J, Barton GM (2014) MyD88: a central player in innate immune signaling. F1000Prime Rep 6:97.  https://doi.org/10.12703/P6-97 Google Scholar
  24. Ding F, Li F, Li Y, Hou X, Ma Y, Zhang N, Ma J, Zhang R, Lang B, Wang H, Wang Y (2016) HSP60 mediates the neuroprotective effects of curcumin by suppressing microglial activation. Exp Ther Med 12:823–828.  https://doi.org/10.3892/etm.2016.3413 Google Scholar
  25. Dong W, Yang B, Wang L, Li B, Guo X, Zhang M, Jiang Z, Fu J, Pi J, Guan D, Zhao R (2018) Curcumin plays neuroprotective roles against traumatic brain injury partly via Nrf2 signaling. Toxicol Appl Pharmacol 346:28–36.  https://doi.org/10.1016/j.taap.2018.03.020 Google Scholar
  26. Eun CS, Lim JS, Lee J, Lee SP, Yang SA (2017) The protective effect of fermented Curcuma longa L. on memory dysfunction in oxidative stress-induced C6 gliomal cells, proinflammatory-activated BV2 microglial cells, and scopolamine-induced amnesia model in mice. BMC Complement Altern Med 17:367.  https://doi.org/10.1186/s12906-017-1880-3 Google Scholar
  27. Ganjali S, Blesso CN, Banach M, Pirro M, Majeed M, Sahebkar A (2017) Effects of curcumin on HDL functionality. Pharmacol Res 119:208–218.  https://doi.org/10.1016/j.phrs.2017.02.008 Google Scholar
  28. Ghandadi M, Sahebkar A (2017) Curcumin: an effective inhibitor of interleukin-6. Curr Pharm Des 23:921–931.  https://doi.org/10.2174/1381612822666161006151605 Google Scholar
  29. Ghosh S, Banerjee S, Sil PC (2015) The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: a recent update. Food Chem Toxicol 83:111–124.  https://doi.org/10.1016/j.fct.2015.05.022 Google Scholar
  30. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, Merad M (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–845.  https://doi.org/10.1126/science.1194637 Google Scholar
  31. Guo L, Xing Y, Pan R, Jiang M, Gong Z, Lin L, Wang J, Xiong G, Dong J (2013) Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis. PLoS One 8:e70565.  https://doi.org/10.1371/journal.pone.0070565 Google Scholar
  32. Gupta SC, Kismali G, Aggarwal BB (2013) Curcumin, a component of turmeric: from farm to pharmacy. Biofactors 39:2–13Google Scholar
  33. Hamzehzadeh L, Atkin SL, Majeed M, Butler AE, Sahebkar A (2018) The versatile role of curcumin in cancer prevention and treatment: a focus on PI3K/AKT pathway. J Cell Physiol 233:6530–6537.  https://doi.org/10.1002/jcp.26620 Google Scholar
  34. Hanisch UK (2013) Functional diversity of microglia - how heterogeneous are they to begin with? Front Cell Neurosci 7:65.  https://doi.org/10.3389/fncel.2013.00065 Google Scholar
  35. He LF, Chen HJ, Qian LH, Chen GY, Buzby JS (2010) Curcumin protects pre-oligodendrocytes from activated microglia in vitro and in vivo. Brain Res 1339:60–69.  https://doi.org/10.1016/j.brainres.2010.04.014 Google Scholar
  36. He GL, Liu Y, Li M, Chen CH, Gao P, Yu ZP, Yang XS (2014) The amelioration of phagocytic ability in microglial cells by curcumin through the inhibition of EMF-induced pro-inflammatory responses. J Neuroinflammation 11:49.  https://doi.org/10.1186/1742-2094-11-49 Google Scholar
  37. He GL, Luo Z, Yang J, Shen TT, Chen Y, Yang XS (2016) Curcumin ameliorates the reduction effect of PGE2 on fibrillar beta-amyloid peptide (1-42)-induced microglial phagocytosis through the inhibition of EP2-PKA signaling in N9 microglial cells. PLoS One 11:e0147721.  https://doi.org/10.1371/journal.pone.0147721 Google Scholar
  38. Hesari A, Ghasemi F, Salarinia R, Biglari H, Tabar Molla Hassan A, Abdoli V, Mirzaei H (2018) Effects of curcumin on NF-kappaB, AP-1, and Wnt/beta-catenin signaling pathway in hepatitis B virus infection. J Cell Biochem 119:7898–7904.  https://doi.org/10.1002/jcb.26829 Google Scholar
  39. Hidalgo-Lanussa O, Avila-Rodriguez M, Baez-Jurado E, Zamudio J, Echeverria V et al (2018) Tibolone reduces oxidative damage and inflammation in microglia stimulated with palmitic acid through mechanisms involving estrogen receptor. Beta Mol Neurobiol 55:5462–5477.  https://doi.org/10.1007/s12035-017-0777-y Google Scholar
  40. Hillmer EJ, Zhang H, Li HS, Watowich SS (2016) STAT3 signaling in immunity. Cytokine Growth Factor Rev 31:1–15.  https://doi.org/10.1016/j.cytogfr.2016.05.001 Google Scholar
  41. Hoppe JB, Coradini K, Frozza RL, Oliveira CM, Meneghetti AB, Bernardi A, Pires ES, Beck RCR, Salbego CG (2013) Free and nanoencapsulated curcumin suppress beta-amyloid-induced cognitive impairments in rats: involvement of BDNF and Akt/GSK-3beta signaling pathway. Neurobiol Learn Mem 106:134–144.  https://doi.org/10.1016/j.nlm.2013.08.001 Google Scholar
  42. Hosseini S, Chamani J, Rahimi H, Azmoodeh N, Ghasemi F et al (2018) An in vitro study on curcumin delivery by nano-micelles for esophageal squamous cell carcinoma (KYSE-30). Rep Biochem Mol Biol 6:137–143Google Scholar
  43. Hu S, Maiti P, Ma Q, Zuo X, Jones MR, Cole GM, Frautschy SA (2015) Clinical development of curcumin in neurodegenerative disease. Expert Rev Neurother 15:629–637.  https://doi.org/10.1586/14737175.2015.1044981 Google Scholar
  44. Huang Y, Xu Z, Xiong S, Sun F, Qin G, Hu G, Wang J, Zhao L, Liang YX, Wu T, Lu Z, Humayun MS, So KF, Pan Y, Li N, Yuan TF, Rao Y, Peng B (2018) Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion. Nat Neurosci 21:530–540.  https://doi.org/10.1038/s41593-018-0090-8 Google Scholar
  45. Iglesias J, Morales L, Barreto GE (2017) Metabolic and inflammatory adaptation of reactive astrocytes: role of PPARs. Mol Neurobiol 54:2518–2538.  https://doi.org/10.1007/s12035-016-9833-2 Google Scholar
  46. Imbimbo B, Solfrizzi V, Panza F (2010) Are NSAIDs useful to treat Alzheimer’s disease or mild cognitive impairment? Front Aging Neurosci 2.  https://doi.org/10.3389/fnagi.2010.00019
  47. Iranshahi M, Sahebkar A, Takasaki M, Konoshima T, Tokuda H (2009) Cancer chemopreventive activity of the prenylated coumarin, umbelliprenin, in vivo. Eur J Cancer Prev 18:412–415.  https://doi.org/10.1097/CEJ.0b013e32832c389e Google Scholar
  48. Jack CS, Arbour N, Manusow J, Montgrain V, Blain M, McCrea E, Shapiro A, Antel JP (2005) TLR signaling tailors innate immune responses in human microglia and astrocytes. J Immunol 175:4320–4330Google Scholar
  49. Jacob A, Wu R, Zhou M, Wang P (2007) Mechanism of the anti -inflammatory effect of curcumin: PPAR-gamma Activation. PPAR Res 2007:89369.  https://doi.org/10.1155/2007/89369 Google Scholar
  50. Karimian MS, Pirro M, Johnston TP, Majeed M, Sahebkar A (2017a) Curcumin and endothelial function: evidence and mechanisms of protective effects. Curr Pharm Des 23:2462–2473.  https://doi.org/10.2174/1381612823666170222122822 Google Scholar
  51. Karimian MS, Pirro M, Majeed M, Sahebkar A (2017b) Curcumin as a natural regulator of monocyte chemoattractant protein-1. Cytokine Growth Factor Rev 33:55–63.  https://doi.org/10.1016/j.cytogfr.2016.10.001 Google Scholar
  52. Karlstetter M, Lippe E, Walczak Y, Moehle C, Aslanidis A, Mirza M, Langmann T (2011) Curcumin is a potent modulator of microglial gene expression and migration. J Neuroinflammation 8:125.  https://doi.org/10.1186/1742-2094-8-125 Google Scholar
  53. Kaur H, Patro I, Tikoo K, Sandhir R (2015) Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy. Neurochem Int 89:40–50.  https://doi.org/10.1016/j.neuint.2015.07.009 Google Scholar
  54. Keihanian F, Saeidinia A, Bagheri RK, Johnston TP, Sahebkar A (2018) Curcumin, hemostasis, 584 thrombosis, and coagulation. J Cell Physiol 233:4497–4511.  https://doi.org/10.1002/jcp.26249 Google Scholar
  55. Kettenmann H, Hanisch UK, Noda M, Verkhratsky A (2011) Physiology of microglia. Physiol Rev 91:461–553.  https://doi.org/10.1152/physrev.00011.2010 Google Scholar
  56. Kodali M, Hattiangady B, Shetty GA, Bates A, Shuai B, Shetty AK (2018) Curcumin treatment leads to better cognitive and mood function in a model of Gulf War Illness with enhanced neurogenesis, and alleviation of inflammation and mitochondrial dysfunction in the hippocampus. Brain Behav Immun 69:499–514.  https://doi.org/10.1016/j.bbi.2018.01.009 Google Scholar
  57. Lanussa OH, Avila-Rodriguez M, Garcia-Segura LM, Gonzalez J, Echeverria V et al (2016) Microglial dependent protective effects of neuroactive steroids. CNS Neurol Disord Drug Targets 15:242–249Google Scholar
  58. Lao CD, Ruffin MT 4th, Normolle D, Health DD, Murray SI et al (2006) Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 6:10.  https://doi.org/10.1186/1472-6882-6-10 Google Scholar
  59. Lee KH, Chow YL, Sharmili V, Abas F, Alitheen NB et al (2012) BDMC33, a curcumin derivative suppresses inflammatory responses in macrophage-like cellular system: role of inhibition in NF-kappaB and MAPK signaling pathways. Int J Mol Sci 13:2985–3008.  https://doi.org/10.3390/ijms13032985 Google Scholar
  60. Lelli D, Sahebkar A, Johnston TP, Pedone C (2017) Curcumin use in pulmonary diseases: state of the art and future perspectives. Pharmacol Res 115:133–148.  https://doi.org/10.1016/j.phrs.2016.11.017 Google Scholar
  61. Liang G, Li X, Chen L, Yang S, Wu X, Studer E, Gurley E, Hylemon PB, Ye F, Li Y, Zhou H (2008) Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin. Bioorg Med Chem Lett 18:1525–1529Google Scholar
  62. Liu W, Ma H, DaSilva NA, Rose KN, Johnson SL et al (2016a) Development of a neuroprotective potential algorithm for medicinal plants. Neurochem Int 100:164–177.  https://doi.org/10.1016/j.neuint.2016.09.014 Google Scholar
  63. Liu ZJ, Li ZH, Liu L, Tang WX, Wang Y, Dong MR, Xiao C (2016b) Curcumin attenuates beta-amyloid-induced neuroinflammation via activation of peroxisome proliferator-activated receptor-gamma function in a rat model of Alzheimer’s disease. Front Pharmacol 7:261.  https://doi.org/10.3389/fphar.2016.00261 Google Scholar
  64. Liu Z, Ran Y, Huang S, Wen S, Zhang W, Liu X, Ji Z, Geng X, Ji X, du H, Leak RK, Hu X (2017) Curcumin protects against ischemic stroke by titrating microglia/macrophage polarization. Front Aging Neurosci 9:233.  https://doi.org/10.3389/fnagi.2017.00233 Google Scholar
  65. Lund H, Pieber M, Parsa R, Grommisch D, Ewing E, Kular L, Han J, Zhu K, Nijssen J, Hedlund E, Needhamsen M, Ruhrmann S, Guerreiro-Cacais AO, Berglund R, Forteza MJ, Ketelhuth DFJ, Butovsky O, Jagodic M, Zhang XM, Harris RA (2018) Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-beta signaling. Nat Immunol 19:1–7.  https://doi.org/10.1038/s41590-018-0091-5 Google Scholar
  66. Maiti P, Paladugu L, Dunbar GL (2018) Solid lipid curcumin particles provide greater anti -amyloid, anti-inflammatory and neuroprotective effects than curcumin in the 5xFAD mouse model of Alzheimer’s disease. BMC Neurosci 19:7.  https://doi.org/10.1186/s12868-018-0406-3 Google Scholar
  67. Mantovani A, Sica A, Locati M (2005) Macrophage polarization comes of age. Immunity 23:344–346.  https://doi.org/10.1016/j.immuni.2005.10.001 Google Scholar
  68. Martinez FO, Gordon S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 6:13.  https://doi.org/10.12703/p6-13 Google Scholar
  69. Mazzolani F, Togni S (2013) Oral administration of a curcumin-phospholipid delivery system for the treatment of central serous chorioretinopathy: a 12-month follow-up study. Clin Ophthalmol 7:939–945.  https://doi.org/10.2147/OPTH.S45820 Google Scholar
  70. Miłobȩdzka J, Kostanecki S, Lampe V (1910) Zur Kenntnis des Curcumins Berichte der deutschen chemischen. Gesellschaft 43:2163–2170.  https://doi.org/10.1002/cber.191004302168 Google Scholar
  71. Mirzaei H, Naseri G, Rezaee R, Mohammadi M, Banikazemi Z, Mirzaei HR, Salehi H, Peyvandi M, Pawelek JM, Sahebkar A (2016) Curcumin: a new candidate for melanoma therapy? Int J Cancer 139:1683–1695.  https://doi.org/10.1002/ijc.30224 Google Scholar
  72. Mokhtari-Zaer A, Marefati N, Atkin SL, Butler AE, Sahebkar A (2018) The protective role of curcumin in myocardial ischemia-reperfusion injury. J Cell Physiol 234:214–222.  https://doi.org/10.1002/jcp.26848 Google Scholar
  73. Momtazi AA, Sahebkar A (2016) Difluorinated curcumin: a promising curcumin analogue with improved anti-tumor activity and pharmacokinetic profile. Curr Pharm Des 22:4386–4397.  https://doi.org/10.2174/1381612822666160527113501 Google Scholar
  74. Momtazi AA, Derosa G, Maffioli P, Banach M, Sahebkar A (2016a) Role of microRNAs in the therapeutic effects of curcumin in non-cancer diseases. Mol Diagn Ther 20:335–345.  https://doi.org/10.1007/s40291-016-0202-7 Google Scholar
  75. Momtazi AA, Shahabipour F, Khatibi S, Johnston TP, Pirro M et al (2016b) Curcumin as a MicroRNA regulator in cancer: a review. Rev Physiol Biochem Pharmacol 171:1–38.  https://doi.org/10.1007/112_2016_3 Google Scholar
  76. Morales I, Guzman-Martinez L, Cerda-Troncoso C, Farias GA, Maccioni RB (2014) Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci 8:112.  https://doi.org/10.3389/fncel.2014.00112 Google Scholar
  77. Mukherjee S, Baidoo J, Fried A, Atwi D, Dolai S, Boockvar J, Symons M, Ruggieri R, Raja K, Banerjee P (2016) Curcumin changes the polarity of tumor associated microglia and eliminates glioblastoma. Int J Cancer 139:2838–2849.  https://doi.org/10.1002/ijc.30398 Google Scholar
  78. Mukherjee S, Fried A, Hussaini R, White R, Baidoo J, Yalamanchi S, Banerjee P (2018) Phytosomal curcumin causes natural killer cell-dependent repolarization of glioblastoma (GBM) tumor-associated microglia/macrophages and elimination of GBM and GBM stem cells. J Exp Clin Cancer Res 37:168.  https://doi.org/10.1186/s13046-018-0792-5 Google Scholar
  79. Naeimi R, Safarpour F, Hashemian M, Tashakorian H, Ahmadian SR, Ashrafpour M, Ghasemi-Kasman M (2018) Curcumin-loaded nanoparticles ameliorate glial activation and improve myelin repair in lyolecithin-induced focal demyelination model of rat corpus callosum. Neurosci Lett 674:1–10.  https://doi.org/10.1016/j.neulet.2018.03.018 Google Scholar
  80. Napoli I, Neumann H (2009) Microglial clearance function in health and disease. Neuroscience 158:1030–1038Google Scholar
  81. Niskanen J, Zhang I, Xue Y, Golberg D, Maysinger D, Winnik FM (2016) Boron nitride nanotubes as vehicles for intracellular delivery of fluorescent drugs and probes. Nanomed (Lond) 11:447–463.  https://doi.org/10.2217/nnm.15.214 Google Scholar
  82. Panahi Y, Khalili N, Hosseini MS, Abbasinazari M, Sahebkar A (2014) Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial. Complement Ther Med 22:851–857.  https://doi.org/10.1016/j.ctim.2014.07.006 Google Scholar
  83. Panahi Y, Hosseini MS, Khalili N, Naimi E, Majeed M, Sahebkar A (2015) 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 34:1101–1108.  https://doi.org/10.1016/j.clnu.2014.12.019 Google Scholar
  84. Panahi Y, Ghanei M, Hajhashemi A, Sahebkar A (2016a) Effects of curcuminoids-piperine combination on systemic oxidative stress, clinical symptoms and quality of life in subjects with chronic pulmonary complications due to sulfur mustard: a randomized controlled trial. J Diet Suppl 13:93–105.  https://doi.org/10.3109/19390211.2014.952865 Google Scholar
  85. Panahi Y, Kianpour P, Mohtashami R, Jafari R, Simental-Mendiá LE et al (2016b) 676 curcumin lowers serum lipids and uric acid in subjects with nonalcoholic fatty liver disease: a randomized controlled trial. J Cardiovasc Pharmacol 68:223–229.  https://doi.org/10.1097/FJC.0000000000000406 Google Scholar
  86. Panahi Y, Khalili N, Sahebi E, Namazi S, Karimian MS, Majeed M, Sahebkar A (2017a) Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial. Inflammopharmacology 25:25–31.  https://doi.org/10.1007/s10787-016-0301-4 Google Scholar
  87. Panahi Y, Kianpour P, Mohtashami R, Jafari R, Simental -Mendía LE et al (2017b) Efficacy and safety of phytosomal curcumin in non-alcoholic fatty liver disease: a randomized controlled trial. Drug Res 67:244–251.  https://doi.org/10.1055/s-0043-100019 Google Scholar
  88. Panahi Y, Khalili N, Sahebi E, Namazi S, Simental -Mendía LE et al (2018) Effects of curcuminoids plus piperine on glycemic, hepatic and inflammatory biomarkers in patients with type 2 diabetes mellitus: a randomized double-blind placebo-controlled trial. Drug Res 68:403–409.  https://doi.org/10.1055/s-0044-101752 Google Scholar
  89. Parada E, Buendia I, Navarro E, Avendano C, Egea J et al (2015) Microglial HO-1 induction by curcumin provides antioxidant, antineuroinflammatory, and glioprotective effects. Mol Nutr Food Res 59:1690–1700.  https://doi.org/10.1002/mnfr.201500279 Google Scholar
  90. Parsamanesh N, Moossavi M, Bahrami A, Butler AE, Sahebkar A (2018) Therapeutic potential of curcumin in diabetic complications. Pharmacol Res 136:181–193.  https://doi.org/10.1016/j.phrs.2018.09.012 Google Scholar
  91. Ransohoff RM (2016) A polarizing question: do M1 and M2 microglia exist? Nat Neurosci 19:987–991.  https://doi.org/10.1038/nn.4338 Google Scholar
  92. Ransohoff RM, Cardona AE (2010) The myeloid cells of the central nervous system parenchyma. Nature 468:253–262.  https://doi.org/10.1038/nature09615 Google Scholar
  93. Réu P, Khosravi A, Bernard S, Mold JE, Salehpour M, Alkass K, Perl S, Tisdale J, Possnert G, Druid H, Frisén J (2017) The lifespan and turnover of microglia in the human brain. Cell Rep 20:779–784.  https://doi.org/10.1016/j.celrep.2017.07.004 Google Scholar
  94. Riazi K, Galic MA, Kentner AC, Reid AY, Sharkey KA et al (2015) Microglia-dependent alteration of glutamatergic synaptic transmission and plasticity in the hippocampus during peripheral inflammation. J Neurosci 35:4942–4952Google Scholar
  95. Rossi F, Lewis C (2018) Microglia’s heretical self –renewal. Nat Neurosci 21:455–456.  https://doi.org/10.1038/s41593-018-0123-3 Google Scholar
  96. Saeidinia A, Keihanian F, Butler AE, Bagheri RK, Atkin SL, Sahebkar A (2018) Curcumin in heart failure: a choice for complementary therapy? Pharmacol Res 131:112–119.  https://doi.org/10.1016/j.phrs.2018.03.009 Google Scholar
  97. Sahebkar A (2010) Molecular mechanisms for curcumin benefits against ischemic injury. Fertil Steril 94:e75–e76; author reply e77.  https://doi.org/10.1016/j.fertnstert.2010.07.1071 Google Scholar
  98. Sahebkar A, Serban MC, Ursoniu S, Banach M (2015) Effect of curcuminoids on oxidative stress: a systematic review and meta-analysis of randomized controlled trials. J Funct Foods 18:898–909.  https://doi.org/10.1016/j.jff.2015.01.005 Google Scholar
  99. Sahebkar A, Cicero AFG, Simental-Mendía LE, Aggarwal BB, Gupta SC (2016) Curcumin downregulates human tumor necrosis factor-α levels: a systematic review and meta-analysis ofrandomized controlled trials. Pharmacol Res 107:234–242.  https://doi.org/10.1016/j.phrs.2016.03.026 Google Scholar
  100. Sawikr Y, Yarla NS, Peluso I, Kamal MA, Aliev G et al (2017) Neuroinflammation in Alzheimer’s disease: the preventive and therapeutic potential of polyphenolic nutraceuticals. Adv Protein Chem Struct Biol 108:33–57.  https://doi.org/10.1016/bs.apcsb.2017.02.001 Google Scholar
  101. Shakeri A, Sahebkar A (2016) Optimized curcumin formulations for the treatment of Alzheimer’s disease: a patent evaluation. J Neurosci Res 94:111–113.  https://doi.org/10.1002/jnr.23696 Google Scholar
  102. Shakeri A, Ward N, Panahi Y, Sahebkar A (2018) Anti-angiogenic activity of curcumin in cancer therapy: a narrative review. Curr Vasc Pharmacol 17:262–269.  https://doi.org/10.2174/1570161116666180209113014 Google Scholar
  103. Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A et al (2004) Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10:6847–6854.  https://doi.org/10.1158/1078-0432.CCR-04-0744 Google Scholar
  104. Sharma N, Sharma S, Nehru B (2017) Curcumin protects dopaminergic neurons against inflammation mediated damage and improves motor dysfunction induced by single intranigral lipopolysaccharide injection. Inflammopharmacology 25:351–368.  https://doi.org/10.1007/s10787-017-0346-z Google Scholar
  105. Shi X, Zheng Z, Li J, Xiao Z, Qi W, Zhang A, Wu Q, Fang Y (2015) Curcumin inhibits Abeta-induced microglial inflammatory responses in vitro: involvement of ERK1/2 and p38 signaling pathways. Neurosci Lett 594:105–110.  https://doi.org/10.1016/j.neulet.2015.03.045 Google Scholar
  106. Sorrenti V, Contarini G, Sut S, Dall'Acqua S, Confortin F et al (2018) Curcumin 724 prevents acute neuroinflammation and long-term memory impairment induced by systemic lipopolysaccharide in mice. Front Pharmacol 9:183.  https://doi.org/10.3389/fphar.2018.00183 Google Scholar
  107. Sousa C, Biber K, Michelucci A (2017) Cellular and molecular characterization of microglia: a unique immune cell population. Front Immunol 8:198.  https://doi.org/10.3389/fimmu.2017.00198 Google Scholar
  108. Subramaniam A, Shanmugam MK, Perumal E, Li F, Nachiyappan A, Dai X, Swamy SN, Ahn KS, Kumar AP, Tan BKH, Hui KM, Sethi G (2013) Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochim Biophys Acta 1835:46–60.  https://doi.org/10.1016/j.bbcan.2012.10.002 Google Scholar
  109. Tegenge MA, Rajbhandari L, Shrestha S, Mithal A, Hosmane S, Venkatesan A (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 Google Scholar
  110. Teymouri M, Pirro M, Johnston TP, Sahebkar A (2017) Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: a review of chemistry, cellular, molecular, and preclinical features. BioFactors 43:331–346.  https://doi.org/10.1002/biof.1344 Google Scholar
  111. Tocharus J, Jamsuwan S, Tocharus C, Changtam C, Suksamrarn A (2012) Curcuminoid analogs inhibit nitric oxide production from LPS-activated microglial cells. J Nat Med 66:400–405.  https://doi.org/10.1007/s11418-011-0599-6 Google Scholar
  112. Tripanichkul W, Jaroensuppaperch EO (2012) Curcumin protects nigrostriatal dopaminergic neurons and reduces glial activation in 6-hydroxydopamine hemiparkinsonian mice model. Int J Neurosci 122:263–270.  https://doi.org/10.3109/00207454.2011.648760 Google Scholar
  113. Tripanichkul W, Jaroensuppaperch EO (2013) Ameliorating effects of curcumin on 6-OHDA-induced dopaminergic denervation, glial response, and SOD1 reduction in the striatum of hemiparkinsonian mice. Eur Rev Med Pharmacol Sci 17:1360–1368Google Scholar
  114. Tsai YM, Chien CF, Lin LC, Tsai TH (2011) Curcumin and its nano-formulation: the kinetics of tissue distribution and blood-brain barrier penetration. Int J Pharm 416:331–338.  https://doi.org/10.1016/j.ijpharm.2011.06.030 Google Scholar
  115. Vainchtein ID, Vinet J, Brouwer N, Brendecke S, Biagini G, Biber K, Boddeke HWGM, Eggen BJL (2014) In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed. Glia 62:1724–1735.  https://doi.org/10.1002/glia.22711 Google Scholar
  116. Valverde Y, Benson B, Gupta M, Gupta K (2016) Spinal glial activation and oxidative stress are alleviated by treatment with curcumin or coenzyme Q in sickle mice. Haematologica 101:e44–e47Google Scholar
  117. Venigalla M, Sonego S, Gyengesi E, Sharman MJ, Munch G (2016) Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer’s disease. Neurochem Int 95:63–74.  https://doi.org/10.1016/j.neuint.2015.10.011 Google Scholar
  118. Wang HM, Zhao YX, Zhang S, Liu GD, Kang WY, Tang HD, Ding JQ, Chen SD (2010) PPARgamma agonist curcumin reduces the amyloid-beta-stimulated inflammatory responses in primary astrocytes. J Alzheimers Dis 20:1189–1199.  https://doi.org/10.3233/JAD-2010-091336 Google Scholar
  119. Wang WY, Tan MS, Yu JT, Tan L (2015) Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med 3:136Google Scholar
  120. Wang Y, Yin Z, Gao L, Sun D, Hu X, Xue L, Dai J, Zeng YX, Chen S, Pan B, Chen M, Xie J, Xu H (2017) Curcumin delays retinal degeneration by regulating microglia activation in the retina of rd1 mice. Cell Physiol Biochem 44:479–493.  https://doi.org/10.1159/000485085 Google Scholar
  121. Xu MX, Yu R, Shao LF, Zhang YX, Ge CX, Liu XM, Wu WY, Li JM, Kong LD (2016) Up-regulated fractalkine (FKN) and its receptor CX3CR1 are involved in fructose-induced neuroinflammation: suppression by curcumin. Brain Behav Immun 58:69–81.  https://doi.org/10.1016/j.bbi.2016.01.001 Google Scholar
  122. Yang S, Zhang D, Hu X, Qian S, Liu J et al (2008) Curcumin protects dopaminergic 770 neuron against LPS induced neurotoxicity in primary rat neuron/glia culture. Neurochem Res 33:2044–2053.  https://doi.org/10.1007/s11064-008-9675-z Google Scholar
  123. Yu Y, Shen Q, Lai Y, Park SY, Ou X, Lin D, Jin M, Zhang W (2018) Anti-inflammatory effects of curcumin in microglial cells. Front Pharmacol 9:386.  https://doi.org/10.3389/fphar.2018.00386 Google Scholar
  124. Yuan J, Liu W, Zhu H, Zhang X, Feng Y, Chen Y, Feng H, Lin J (2017) Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice. J Surg Res 207:85–91.  https://doi.org/10.1016/j.jss.2016.08.090 Google Scholar
  125. Yue YK, Mo B, Zhao J, Yu YJ, Liu L, Yue CL, Liu W (2014) Neuroprotective effect of curcumin against oxidative damage in BV-2 microglia and high intraocular pressure animal model. J Ocul Pharmacol Ther 30:657–664.  https://doi.org/10.1089/jop.2014.0022 Google Scholar
  126. Zabihi NA, Pirro M, Johnston TP, Sahebkar A (2017) Is there a role for curcumin supplementation in the treatment of non-alcoholic fatty liver disease? The data suggest yes. Curr Pharm Des 23:969–982.  https://doi.org/10.2174/1381612822666161010115235 Google Scholar
  127. Zhang L, Wu C, Zhao S, Yuan D, Lian G, Wang X, Wang L, Yang J (2010) Demethoxycurcumin, a natural derivative of curcumin attenuates LPS-induced pro-inflammatory responses through down-regulation of intracellular ROS-related MAPK/NF-kappaB signaling pathways in N9 microglia induced by lipopolysaccharide. Int Immunopharmacol 10:331–338.  https://doi.org/10.1016/j.intimp.2009.12.004 Google Scholar
  128. Zhang ZY, Jiang M, Fang J, Yang MF, Zhang S, Yin YX, Li DW, Mao LL, Fu XY, Hou YJ, Fu XT, Fan CD, Sun BL (2017) Enhanced therapeutic potential of nano-curcumin against subarachnoid hemorrhage-induced blood-brain barrier disruption through inhibition of inflammatory response and oxidative stress. Mol Neurobiol 54:1–14.  https://doi.org/10.1007/s12035-015-9635-y Google Scholar
  129. Zhou J, Miao H, Li X, Hu Y, Sun H, Hou Y (2017) Curcumin inhibits placental inflammation to ameliorate LPS induced adverse pregnancy outcomes in mice via upregulation of phosphorylated. Akt Inflamm Res 66:177–185.  https://doi.org/10.1007/s00011-016-1004-4 Google Scholar
  130. Zhu H, Bian C, Yuan JC, Chu WH, Xiang X, Chen F, Wang CS, Feng H, Lin JK (2014) Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-kappaB signaling pathway in experimental traumatic brain injury. J Neuroinflammation 11:59Google Scholar
  131. Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L, Miller D, Zhang HG (2011) Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 19:1769–1779.  https://doi.org/10.1038/mt.2011.164 Google Scholar
  132. Zusso M, Mercanti G, Belluti F, Di Martino RMC, Pagetta A et al (2017) Phenolic 1,3-diketones attenuate lipopolysaccharide-induced inflammatory response by an alternative magnesium-mediated mechanism. Br J Pharmacol 174:1090–1103.  https://doi.org/10.1111/bph.13746 Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Blood Transfusion Research CenterHigh Institute for Research and Education in Transfusion MedicineTehranIran
  2. 2.Department of Biotechnology, Faculty of MedicineArak University of Medical SciencesArakIran
  3. 3.Departamento de Nutrición y Bioquímica, Facultad de CienciasPontificia Universidad JaverianaBogotáColombia
  4. 4.Instituto de Ciencias BiomédicasUniversidad Autónoma de ChileSantiagoChile
  5. 5.Department of Pharmacology, School of Medical SciencesUniversity of OtagoDunedinNew Zealand
  6. 6.Neurogenic Inflammation Research CenterMashhad University of Medical SciencesMashhadIran
  7. 7.Biotechnology Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran
  8. 8.School of PharmacyMashhad University of Medical SciencesMashhadIran
  9. 9.Department of Medical Biotechnology, School of MedicineMashhad University of Medical SciencesMashhadIran

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