Curcumin as a potential modulator of M1 and M2 macrophages: new insights in atherosclerosis therapy

  • Amir Abbas Momtazi-BorojeniEmail author
  • Elham Abdollahi
  • Banafsheh NikfarEmail author
  • Shahla Chaichian
  • Mahnaz Ekhlasi-Hundrieser


Accumulation of macrophages within the artery wall is an eminent feature of atherosclerotic plaques. Macrophages are influenced by various plaque microenvironmental stimuli, such as oxidized lipids, cytokines, and senescent erythrocytes, and thereby polarize into two main phenotypes called proinflammatory M1 and anti-inflammatory M2 macrophages. In the hemorrhagic zones of atheroma, upon exposure to iron, sequestration of iron by M1 macrophages results in an uncontrolled proinflammatory phenotype impairing wound healing, while M2 macrophages phagocytose both apoptotic cells and senescent erythrocytes. M1 macrophages are prominent phenotype in the unstable plaques, in which plaque shoulder contains macrophages mainly present markers of M1 phenotype, whereas the fibrous cap encompassing the necrotic lipid core content macrophages expressed markers of both M1 and M2 subtypes. The abovementioned findings suggest macrophage modulation as a potent approach for atherosclerosis therapy. Curcumin is a polyphenol dietary derived from turmeric with numerous pharmacological activities. Recent in vitro and in vivo studies have indicated that curcumin exerted lipid-lowering effects, and also can modulate function of different macrophage subsets in various macrophage-involved diseases. The current review aimed to present role of macrophage subtypes in atherosclerosis development and progression, and to understand effect of curcumin on macrophage polarization and foam cell formation in the atherosclerosis lesions. Overall, we would address important targets for macrophage modulation in atherosclerotic plaques.


Atherosclerosis Atherosclerotic plaque Curcumin Inflammation M1 and M2 macrophages 



ATP-binding cassette transporter


Adipocyte protein


CD163 antigen-like 1


Cholesterol efflux regulatory protein




Extracellular signal–regulated kinases


Fatty acid-binding proteins


c-Jun N-terminal kinase


Inducible nitric-oxide synthase


Mitogen-activated protein kinase


Nuclear factor kappa-light-chain-enhancer of activated B cells


Selenoprotein P


Granulocyte-macrophage colony stimulating factor


Interferon gamma




Low-density lipoprotein cholesterol




Liver X receptor alpha


Macrophage colony-stimulating factor


Nuclear factor (erythroid-derived 2)-like 2




Scavenger receptors


Tumor necrosis factor




Phosphoinositide 3-kinase


Peroxisome proliferator-activated receptor gamma


Reverse cholesterol transport


Reactive oxygen species




T helper 1


Toll-like receptors


Tumor necrosis factor alpha


Transforming growth factor β


Vascular smooth muscle cells



The authors would like to say special thanks to the cooperation of Pars Advanced and Minimally Invasive Medical Manners Research Center - Pars Hospital, Nanotechnology Research Center, and Department of Medical Biotechnology of Mashhad University of Medical Sciences for their kindness.

Compliance with ethical standards

Conflict of interest

The authors have no direct conflict of interests related to the content of this review.


  1. 1.
    Moss JW, Ramji DP (2016) Nutraceutical therapies for atherosclerosis. Nat Rev Cardiol 13:513–532CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Lusis AJ (2000) Atherosclerosis. Nature 407(6801):233–241CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340(2):115–126CrossRefGoogle Scholar
  4. 4.
    Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M (1995) Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc Natl Acad Sci 92(18):8264–8268CrossRefPubMedGoogle Scholar
  5. 5.
    Peiser L, Mukhopadhyay S, Gordon S (2002) Scavenger receptors in innate immunity. Curr Opin Immunol 14(1):123–128CrossRefPubMedGoogle Scholar
  6. 6.
    Janeway CA Jr, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20(1):197–216CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Tabas I (2005) Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency. Arterioscler Thromb Vasc Biol 25(11):2255–2264CrossRefPubMedGoogle Scholar
  8. 8.
    Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19(1):71–82CrossRefGoogle Scholar
  9. 9.
    Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5(12):953–964CrossRefPubMedGoogle Scholar
  10. 10.
    Jenkins SJ, Ruckerl D, Cook PC, Jones LH, Finkelman FD, van Rooijen N, MacDonald AS, Allen JE (2011) Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science 332(6035):1284–1288CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Robbins CS, Hilgendorf I, Weber GF, Theurl I, Iwamoto Y, Figueiredo JL, Gorbatov R, Sukhova GK, Gerhardt LMS, Smyth D, Zavitz CCJ, Shikatani EA, Parsons M, van Rooijen N, Lin HY, Husain M, Libby P, Nahrendorf M, Weissleder R, Swirski FK (2013) Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat Med 19(9):1166–1172CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Jenkins SJ et al (2013) IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1. J Exp Med 210:2477. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Biswas SK, Chittezhath M, Shalova IN, Lim JY (2012) Macrophage polarization and plasticity in health and disease. Immunol Res 53(1–3):11–24CrossRefPubMedGoogle Scholar
  14. 14.
    Murray PJ, Wynn TA (2011) Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11(11):723–737CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3(1):23–35CrossRefPubMedGoogle Scholar
  16. 16.
    Verreck FA et al (2004) Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco) bacteria. Proc Natl Acad Sci U S A 101(13):4560–4565CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Mosser DM (2003) The many faces of macrophage activation. J Leukoc Biol 73(2):209–212CrossRefPubMedGoogle Scholar
  18. 18.
    Mantovani A et al (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25(12):677–686CrossRefPubMedGoogle Scholar
  19. 19.
    Zizzo G, Hilliard BA, Monestier M, Cohen PL (2012) Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction. J Immunol 189(7):3508–3520CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Chinetti-Gbaguidi G et al (2011) Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARγ and LXRα pathways. Circ Res 108:985–995. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Jetten N, Verbruggen S, Gijbels MJ, Post MJ, de Winther MPJ, Donners MMPC (2014) Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo. Angiogenesis 17(1):109–118CrossRefPubMedGoogle Scholar
  22. 22.
    Tabas I (2010) Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol 10(1):36–46CrossRefPubMedGoogle Scholar
  23. 23.
    Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8(12):958–969CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Porcheray F, Viaud S, Rimaniol AC, Léone C, Samah B, Dereuddre-Bosquet N, Dormont D, Gras G (2005) Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol 142(3):481–489PubMedPubMedCentralGoogle Scholar
  25. 25.
    Lee S, Huen S, Nishio H, Nishio S, Lee HK, Choi BS, Ruhrberg C, Cantley LG (2011) Distinct macrophage phenotypes contribute to kidney injury and repair. J Am Soc Nephrol 22(2):317–326CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Chinetti-Gbaguidi G, Colin S, Staels B (2015) Macrophage subsets in atherosclerosis. Nat Rev Cardiol 12(1):10–17CrossRefPubMedGoogle Scholar
  27. 27.
    Stöger JL, Gijbels MJJ, van der Velden S, Manca M, van der Loos CM, Biessen EAL, Daemen MJAP, Lutgens E, de Winther MPJ (2012) Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis 225(2):461–468CrossRefPubMedGoogle Scholar
  28. 28.
    Cho KY, Miyoshi H, Kuroda S, Yasuda H, Kamiyama K, Nakagawara J, Takigami M, Kondo T, Atsumi T (2013) The phenotype of infiltrating macrophages influences arteriosclerotic plaque vulnerability in the carotid artery. J Stroke Cerebrovasc Dis 22(7):910–918CrossRefPubMedGoogle Scholar
  29. 29.
    Shaikh S, Brittenden J, Lahiri R, Brown PAJ, Thies F, Wilson HM (2012) Macrophage subtypes in symptomatic carotid artery and femoral artery plaques. Eur J Vasc Endovasc Surg 44(5):491–497CrossRefPubMedGoogle Scholar
  30. 30.
    Barlis P, Serruys PW, DeVries A, Regar E (2008) Optical coherence tomography assessment of vulnerable plaque rupture: predilection for the plaque ‘shoulder’. Eur Heart J 29(16):2023–2023CrossRefPubMedGoogle Scholar
  31. 31.
    Lee CG, Homer RJ, Zhu Z, Lanone S, Wang X, Koteliansky V, Shipley JM, Gotwals P, Noble P, Chen Q, Senior RM, Elias JA (2001) Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor β1. J Exp Med 194(6):809–822CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nuñez G, Schnurr M, Espevik T, Lien E, Fitzgerald KA, Rock KL, Moore KJ, Wright SD, Hornung V, Latz E (2010) NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464(7293):1357–1361CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Bae YS, Lee JH, Choi SH, Kim S, Almazan F, Witztum JL, Miller YI (2009) Macrophages generate reactive oxygen species in response to minimally oxidized low-density lipoprotein: toll-like receptor 4–and spleen tyrosine kinase–dependent activation of NADPH oxidase 2. Circ Res 104(2):210–218CrossRefPubMedGoogle Scholar
  34. 34.
    Van Tits L et al (2011) Oxidized LDL enhances pro-inflammatory responses of alternatively activated M2 macrophages: a crucial role for Krüppel-like factor 2. Atherosclerosis 214(2):345–349CrossRefPubMedGoogle Scholar
  35. 35.
    Hirose K, Iwabuchi K, Shimada K, Kiyanagi T, Iwahara C, Nakayama H, Daida H (2011) Different responses to oxidized low-density lipoproteins in human polarized macrophages. Lipids Health Dis 10(1):1CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Fang L, Harkewicz R, Hartvigsen K, Wiesner P, Choi SH, Almazan F, Pattison J, Deer E, Sayaphupha T, Dennis EA, Witztum JL, Tsimikas S, Miller YI (2010) Oxidized cholesteryl esters and phospholipids in zebrafish larvae fed a high cholesterol diet macrophage binding and activation. J Biol Chem 285(42):32343–32351CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Sottero B, Gamba P, Longhi M, Robbesyn F, Abuja PM, Schaur RJ, Poli G, Leonarduzzi G (2005) Expression and synthesis of TGFβ1 is induced in macrophages by 9-oxononanoyl cholesterol, a major cholesteryl ester oxidation product. Biofactors 24(1–4):209–216CrossRefPubMedGoogle Scholar
  38. 38.
    Mitchell PL, McLeod RS (2008) Conjugated linoleic acid and atherosclerosis: studies in animal models. Biochem Cell Biol 86(4):293–301CrossRefPubMedGoogle Scholar
  39. 39.
    McCarthy C, Duffy MM, Mooney D, James WG, Griffin MD, Fitzgerald DJ, Belton O (2013) IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis. FASEB J 27(2):499–510CrossRefPubMedGoogle Scholar
  40. 40.
    Feig JE, Rong JX, Shamir R, Sanson M, Vengrenyuk Y, Liu J, Rayner K, Moore K, Garabedian M, Fisher EA (2011) HDL promotes rapid atherosclerosis regression in mice and alters inflammatory properties of plaque monocyte-derived cells. Proc Natl Acad Sci 108(17):7166–7171CrossRefPubMedGoogle Scholar
  41. 41.
    Hughes JE, Srinivasan S, Lynch KR, Proia RL, Ferdek P, Hedrick CC (2008) Sphingosine-1-phosphate induces an antiinflammatory phenotype in macrophages. Circ Res 102(8):950–958CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Titos E, Rius B, González-Périz A, López-Vicario C, Morán-Salvador E, Martínez-Clemente M, Arroyo V, Clària J (2011) Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype. J Immunol 187(10):5408–5418CrossRefPubMedGoogle Scholar
  43. 43.
    Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF, Oh SF, Spite M (2009) Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med 206(1):15–23CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Wolfs IM, Donners MM, de Winther MP (2011) Differentiation factors and cytokines in the atherosclerotic plaque micro-environment as a trigger for macrophage polarisation. Thromb Haemost 105(05):763–771CrossRefGoogle Scholar
  45. 45.
    Bouhlel MA, Derudas B, Rigamonti E, Dièvart R, Brozek J, Haulon S, Zawadzki C, Jude B, Torpier G, Marx N, Staels B, Chinetti-Gbaguidi G (2007) PPARγ activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab 6(2):137–143CrossRefPubMedGoogle Scholar
  46. 46.
    Waldo SW, Li Y, Buono C, Zhao B, Billings EM, Chang J, Kruth HS (2008) Heterogeneity of human macrophages in culture and in atherosclerotic plaques. Am J Pathol 172(4):1112–1126CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Brochériou I, Maouche S, Durand H, Braunersreuther V, le Naour G, Gratchev A, Koskas F, Mach F, Kzhyshkowska J, Ninio E (2011) Antagonistic regulation of macrophage phenotype by M-CSF and GM-CSF: implication in atherosclerosis. Atherosclerosis 214(2):316–324CrossRefPubMedGoogle Scholar
  48. 48.
    Plenz G, Koenig C, Severs NJ, Robenek H (1997) Smooth muscle cells express granulocyte-macrophage colony-stimulating factor in the undiseased and atherosclerotic human coronary artery. Arterioscler Thromb Vasc Biol 17(11):2489–2499CrossRefPubMedGoogle Scholar
  49. 49.
    Kolodgie FD, Gold HK, Burke AP, Fowler DR, Kruth HS, Weber DK, Farb A, Guerrero LJ, Hayase M, Kutys R, Narula J, Finn AV, Virmani R (2003) Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med 349(24):2316–2325CrossRefPubMedGoogle Scholar
  50. 50.
    Kockx MM, Cromheeke KM, Knaapen MWM, Bosmans JM, de Meyer GRY, Herman AG, Bult H (2003) Phagocytosis and macrophage activation associated with hemorrhagic microvessels in human atherosclerosis. Arterioscler Thromb Vasc Biol 23(3):440–446CrossRefPubMedGoogle Scholar
  51. 51.
    Sindrilaru A, Peters T, Wieschalka S, Baican C, Baican A, Peter H, Hainzl A, Schatz S, Qi Y, Schlecht A, Weiss JM, Wlaschek M, Sunderkötter C, Scharffetter-Kochanek K (2011) An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J Clin Invest 121(3):985–997CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Bories G et al (2013) Liver X receptor (LXR) activation stimulates iron export in human alternative macrophages. Circ Res 113:1196–1205. CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Nielsen MJ, Møller HJ, Moestrup SK (2010) Hemoglobin and heme scavenger receptors. Antioxid Redox Signal 12(2):261–273CrossRefPubMedGoogle Scholar
  54. 54.
    Finn AV, Nakano M, Polavarapu R, Karmali V, Saeed O, Zhao XQ, Yazdani S, Otsuka F, Davis T, Habib A, Narula J, Kolodgie FD, Virmani R (2012) Hemoglobin directs macrophage differentiation and prevents foam cell formation in human atherosclerotic plaques. J Am Coll Cardiol 59(2):166–177CrossRefPubMedGoogle Scholar
  55. 55.
    Vivo SBI (2004) Hemoglobin scavenger receptor CD163 mediates interleukin-10 release and heme oxygenase-1 synthesis. Circ Res 94:119–126CrossRefGoogle Scholar
  56. 56.
    Landis RC, Philippidis P, Domin J, Boyle JJ, Haskard DO (2013) Haptoglobin genotype-dependent anti-inflammatory signaling in CD163. Int J Inflamm 2013:1–7Google Scholar
  57. 57.
    Strimpakos AS, Sharma RA (2008) Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal 10(3):511–546CrossRefPubMedGoogle Scholar
  58. 58.
    Aggarwal BB (2010) Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals. Annu Rev Nutr 30:173–199CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Epstein J, Sanderson IR, MacDonald TT (2010) Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies. Br J Nutr 103(11):1545–1557CrossRefPubMedGoogle Scholar
  60. 60.
    Shehzad A, Ha T, Subhan F, Lee YS (2011) New mechanisms and the anti-inflammatory role of curcumin in obesity and obesity-related metabolic diseases. Eur J Nutr 50(3):151–161CrossRefPubMedGoogle Scholar
  61. 61.
    Momtazi AA et al (2016) Curcumin as a MicroRNA regulator in cancer: a review. Rev Physiol Biochem Pharmacol 171:1–38CrossRefPubMedGoogle Scholar
  62. 62.
    Momtazi AA, Derosa G, Maffioli P, Banach M, Sahebkar A (2016) Role of microRNAs in the therapeutic effects of curcumin in non-cancer diseases. Mol Diagn Ther 20(4):335–345CrossRefPubMedGoogle Scholar
  63. 63.
    Aeineh N et al (2018) Glutathione conjugated polyethylenimine on the surface of Fe3O4 magnetic nanoparticles as a theranostic agent for targeted and controlled curcumin delivery. J Biomater Sci Polym Ed 29(10):1109–1125Google Scholar
  64. 64.
    Momtazi-Borojeni AA et al (2017) Curcumin: a natural modulator of immune cells in systemic lupus erythematosus. Autoimmun Rev 17(2):125–135Google Scholar
  65. 65.
    Schaffer M, Schaffer PM, Zidan J, Sela GB (2011) Curcuma as a functional food in the control of cancer and inflammation. Curr Opin Clin Nutr Metab Care 14(6):588–597CrossRefPubMedGoogle Scholar
  66. 66.
    Zhong Y, Liu T, Guo Z (2012) Curcumin inhibits ox-LDL-induced MCP-1 expression by suppressing the p38MAPK and NF-κB pathways in rat vascular smooth muscle cells. Inflamm Res 61(1):61–67CrossRefPubMedGoogle Scholar
  67. 67.
    Abdollahi E et al (2017) Therapeutic effects of curcumin in inflammatory and immune-mediated diseases: a nature-made jack-of-all-trades? J Cell PhysiolGoogle Scholar
  68. 68.
    Momtazi-Borojeni AA et al Curcumin in advancing treatment for gynecological cancers with developed drug- and radiotherapy-associated resistance. Springer, Berlin, pp 1–23Google Scholar
  69. 69.
    Jang E-M, Choi MS, Jung UJ, Kim MJ, Kim HJ, Jeon SM, Shin SK, Seong CN, Lee MK (2008) Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat–fed hamsters. Metab Clin Exp 57(11):1576–1583CrossRefPubMedGoogle Scholar
  70. 70.
    Kim M, Kim Y (2010) Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet. Nutr Res Pract 4(3):191–195CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Shin SK, Ha TY, McGregor RA, Choi MS (2011) Long-term curcumin administration protects against atherosclerosis via hepatic regulation of lipoprotein cholesterol metabolism. Mol Nutr Food Res 55(12):1829–1840CrossRefPubMedGoogle Scholar
  72. 72.
    Wang MY ( 2012) Spice up your lipids: the effects of curcumin on lipids in humans. Nutr Bytes 16(1)Google Scholar
  73. 73.
    Yang YS, Su YF, Yang HW, Lee YH, Chou JI, Ueng KC (2014) Lipid-lowering effects of curcumin in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled trial. Phytother Res 28(12):1770–1777CrossRefPubMedGoogle Scholar
  74. 74.
    Na LX, Li Y, Pan HZ, Zhou XL, Sun DJ, Meng M, Li XX, Sun CH (2013) Curcuminoids exert glucose-lowering effect in type 2 diabetes by decreasing serum free fatty acids: a double-blind, placebo-controlled trial. Mol Nutr Food Res 57(9):1569–1577CrossRefPubMedGoogle Scholar
  75. 75.
    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(5):851–857CrossRefPubMedGoogle Scholar
  76. 76.
    Panahi Y, Ahmadi Y, Teymouri M, Johnston TP, Sahebkar A (2018) Curcumin as a potential candidate for treating hyperlipidemia: a review of cellular and metabolic mechanisms. J Cell Physiol 233(1):141–152CrossRefPubMedGoogle Scholar
  77. 77.
    Hasan S et al (2014) Curcumin modulation of high fat diet-induced atherosclerosis and steatohepatosis in LDL receptor deficient mice. Atherosclerosis 232(1):40–51CrossRefPubMedGoogle Scholar
  78. 78.
    Zhao JF, Ching LC, Huang YC, Chen CY, Chiang AN, Kou YR, Shyue SK, Lee TS (2012) Molecular mechanism of curcumin on the suppression of cholesterol accumulation in macrophage foam cells and atherosclerosis. Mol Nutr Food Res 56(5):691–701CrossRefPubMedGoogle Scholar
  79. 79.
    Quiles JL et al (2002) Curcuma longa extract supplementation reduces oxidative stress and attenuates aortic fatty streak development in rabbits. Arterioscler Thromb Vasc Biol 22(7):1225–1231CrossRefPubMedGoogle Scholar
  80. 80.
    Ramırez-Tortosa M et al (1999) Oral administration of a turmeric extract inhibits LDL oxidation and has hypocholesterolemic effects in rabbits with experimental atherosclerosis. Atherosclerosis 147(2):371–378CrossRefPubMedGoogle Scholar
  81. 81.
    Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT, Morgan MA, Parker RA, Suttles J, Fazio S, Hotamisligil GS, Linton MRF (2001) Lack of macrophage fatty-acid–binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat Med 7(6):699–705CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Fu Y, Luo N, Lopes-Virella MF, Garvey WT (2002) The adipocyte lipid binding protein (ALBP/aP2) gene facilitates foam cell formation in human THP-1 macrophages. Atherosclerosis 165(2):259–269CrossRefPubMedGoogle Scholar
  83. 83.
    Boord JB, Maeda K, Makowski L, Babaev VR, Fazio S, Linton MRF, Hotamisligil G̈S (2002) Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia. Arterioscler Thromb Vasc Biol 22(10):1686–1691CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Makowski L, Brittingham KC, Reynolds JM, Suttles J, Hotamisligil GS (2005) The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity. Macrophage expression of aP2 impacts peroxisome proliferator-activated receptor gamma and IkappaB kinase activities. J Biol Chem 280(13):12888–12895CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Zingg JM, Hasan ST, Cowan D, Ricciarelli R, Azzi A, Meydani M (2012) Regulatory effects of curcumin on lipid accumulation in monocytes/macrophages. J Cell Biochem 113(3):833–840CrossRefPubMedGoogle Scholar
  86. 86.
    Kou MC, Chiou SY, Weng CY, Wang L, Ho CT, Wu MJ (2013) Curcuminoids distinctly exhibit antioxidant activities and regulate expression of scavenger receptors and heme oxygenase-1. Mol Nutr Food Res 57(9):1598–1610CrossRefPubMedGoogle Scholar
  87. 87.
    Chen F-Y, Zhou J, Guo N, Ma WG, Huang X, Wang H, Yuan ZY (2015) Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis. Biochem Biophys Res Commun 467(4):872–878CrossRefPubMedGoogle Scholar
  88. 88.
    Zingg JM, Hasan ST, Nakagawa K, Canepa E, Ricciarelli R, Villacorta L, Azzi A, Meydani M (2017) Modulation of cAMP levels by high-fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression. Biofactors 43(1):42–53CrossRefPubMedGoogle Scholar
  89. 89.
    Zhou Y, Zhang T, Wang X, Wei X, Chen Y, Guo L, Zhang J, Wang C (2015) Curcumin modulates macrophage polarization through the inhibition of the toll-like receptor 4 expression and its signaling pathways. Cell Physiol Biochem 36(2):631–641CrossRefPubMedGoogle Scholar
  90. 90.
    Youn HS, Saitoh SI, Miyake K, Hwang DH (2006) Inhibition of homodimerization of toll-like receptor 4 by curcumin. Biochem Pharmacol 72(1):62–69CrossRefPubMedGoogle Scholar
  91. 91.
    Chen Y-R, Tan T-H (1998) Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin. Oncogene 17(2):173–178CrossRefPubMedGoogle Scholar
  92. 92.
    Jacob A, Wu R, Zhou M, Wang P (2007) Mechanism of the anti-inflammatory effect of curcumin: PPAR-γ activation. PPAR Res 2007:1–5CrossRefGoogle Scholar
  93. 93.
    Chen F, Guo N, Cao G, Zhou J, Yuan Z (2014) Molecular analysis of curcumin-induced polarization of murine RAW264. 7 macrophages. J Cardiovasc Pharmacol 63(6):544–552CrossRefPubMedGoogle Scholar
  94. 94.
    Gao S, Zhou J, Liu N, Wang L, Gao Q, Wu Y, Zhao Q, Liu P, Wang S, Liu Y, Guo N, Shen Y, Wu Y, Yuan Z (2015) Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13. J Mol Cell Cardiol 85:131–139CrossRefPubMedGoogle Scholar
  95. 95.
    Li B et al (2017) Curcumin attenuates titanium particle-induced inflammation by regulating macrophage polarization in vitro and in vivo. Front Immunol 8:55Google Scholar
  96. 96.
    Medbury H, Tarran SL, Guiffre AK, Williams MM, Lam TH, Vicaretti M, Fletcher JP (2008) Monocytes contribute to the atherosclerotic cap by transformation into fibrocytes. Int Angiol 27(2):114–123PubMedGoogle Scholar
  97. 97.
    Chistiakov DA, Bobryshev YV, Nikiforov NG, Elizova NV, Sobenin IA, Orekhov AN (2015) Macrophage phenotypic plasticity in atherosclerosis: the associated features and the peculiarities of the expression of inflammatory genes. Int J Cardiol 184:436–445CrossRefPubMedGoogle Scholar
  98. 98.
    Bosisio D et al (2002) Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-γ: a molecular basis for priming and synergism with bacterial lipopolysaccharide. Blood 99(9):3427–3431CrossRefPubMedGoogle Scholar
  99. 99.
    Meng Z, Yan C, Deng Q, Gao DF, Niu XL (2013) Curcumin inhibits LPS-induced inflammation in rat vascular smooth muscle cells in vitro via ROS-relative TLR4-MAPK/NF-κB pathways. Acta Pharmacol Sin 34(7):901–911CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Cao J, Han Z, Tian L, Chen K, Fan Y, Ye B, Huang W, Wang C, Huang Z (2014) Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages. J Transl Med 12(1):266CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Gradišar H, Keber MM, Pristovšek P, Jerala R (2007) MD-2 as the target of curcumin in the inhibition of response to LPS. J Leukoc Biol 82(4):968–974CrossRefPubMedGoogle Scholar
  102. 102.
    Kong F et al (2016) Curcumin represses NLRP3 inflammasome activation via TLR4/MyD88/NF-κB and P2X7R signaling in PMA-induced macrophages. Front Pharmacol 7:369PubMedPubMedCentralGoogle Scholar
  103. 103.
    Lee K-H, Chow YL, Sharmili V, Abas F, Alitheen NBM, Shaari K, Israf DA, Lajis NH, Syahida A (2012) BDMC33, a curcumin derivative suppresses inflammatory responses in macrophage-like cellular system: role of inhibition in NF-κB and MAPK signaling pathways. Int J Mol Sci 13(3):2985–3008CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Bai X, Oberley-Deegan RE, Bai A, Ovrutsky AR, Kinney WH, Weaver M, Zhang G, Honda JR, Chan ED (2016) Curcumin enhances human macrophage control of Mycobacterium tuberculosis infection. Respirology 21(5):951–957CrossRefPubMedGoogle Scholar
  105. 105.
    Li H, Sun B (2007) Toll-like receptor 4 in atherosclerosis. J Cell Mol Med 11(1):88–95CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Meng Z, Yan C, Deng Q, Dong X, Duan ZM, Gao DF, Niu XL (2013) Oxidized low-density lipoprotein induces inflammatory responses in cultured human mast cells via toll-like receptor 4. Cell Physiol Biochem 31(6):842–853CrossRefPubMedGoogle Scholar
  107. 107.
    Michelsen KS, Wong MH, Shah PK, Zhang W, Yano J, Doherty TM, Akira S, Rajavashisth TB, Arditi M (2004) Lack of toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc Natl Acad Sci U S A 101(29):10679–10684CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Björkbacka H, Kunjathoor VV, Moore KJ, Koehn S, Ordija CM, Lee MA, Means T, Halmen K, Luster AD, Golenbock DT, Freeman MW (2004) Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways. Nat Med 10(4):416–421CrossRefPubMedGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Halal research center of IRIFDATehranIran
  2. 2.Nanotechnology Research Center, Bu-Ali Research Institute, Student Research CommitteeMashhad University of Medical SciencesMashhadIran
  3. 3.Department of Medical Immunology, Student Research Committee, School of MedicineMashhad University of Medical SciencesMashhadIran
  4. 4.Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars HospitalIran University of Medical SciencesTehranIran
  5. 5.Minimally Invasive Techniques Research Center in Women, Tehran Medical Sciences BranchIslamic Azad UniversityTehranIran
  6. 6.Endometriosis Research Center, Iran University of Medical SciencesTehranIran
  7. 7.Werlhof-InstitutHannoverGermany

Personalised recommendations