Mast cells in meningiomas and brain inflammation

Journal of Neuroinflammation

Volumn 12, Issue 1, 2015, Pages

  Polyzoidis, Stavros ^a   Koletsa, Triantafyllia ^b   Panagiotidou, Smaro ^c   Ashkan, Keyoumars ^a   Theoharides, Theoharis C ^c  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b AHEPA UNIVERSITY HOSPITAL   (Greece)

^c TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOOXYGENASE 2 INHIBITOR; GLUCOCORTICOID; LUTEOLIN; PROSTAGLANDIN SYNTHASE INHIBITOR; QUERCETIN;

BRAIN EDEMA; BRAIN TUMOR; CARCINOGENESIS; CELL FUNCTION; CELL INTERACTION; CELL PROLIFERATION; DRUG POTENTIATION; ENCEPHALITIS; GLIOBLASTOMA; GLIOMA; HEMANGIOBLASTOMA; HUMAN; MAST CELL; MENINGIOMA; NONHUMAN; PATHOGENESIS; REVIEW; SYSTEMATIC REVIEW; ANIMAL; BIBLIOGRAPHIC DATABASE; IMMUNOLOGY; PATHOLOGY; STATISTICS AND NUMERICAL DATA;

ANIMALS; DATABASES, BIBLIOGRAPHIC; ENCEPHALITIS; HUMANS; MAST CELLS; MENINGEAL NEOPLASMS; MENINGIOMA;

EID: 84941758024     PISSN: None     EISSN: 17422094     Source Type: Journal    
DOI: 10.1186/s12974-015-0388-3     Document Type: Review

References (119)

1. Rogers L, Barani I, Chamberlain M, Kaley TJ, McDermott M, Raizer J, et al. Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review. J Neurosurg. 2015;122:4-23.
2. Carroll RS, Zhang J, Black PM. Expression of estrogen receptors alpha and beta in human meningiomas. J Neurooncol. 1999;42:109-16.
3. Maxwell M, Galanopoulos T, Neville-Golden J, Antoniades HN. Expression of androgen and progesterone receptors in primary human meningiomas. J Neurosurg. 1993;78:456-62.
4. Probst-Cousin S, Villagran-Lillo R, Lahl R, Bergmann M, Schmid KW, Gullotta F. Secretory meningioma: clinical, histologic, and immunohistochemical findings in 31 cases. Cancer. 1997;79:2003-15.
5. Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol. 2013;15 Suppl 2:ii1-56.
6. Madhusoodanan S, Patel S, Reinharth J, Hines A, Serper M. Meningioma and psychiatric symptoms: a case report and brief review. Ann Clin Psychiatry. 2015;27:126-33.
7. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97-109.
8. Mirimanoff RO, Dosoretz DE, Linggood RM, Ojemann RG, Martuza RL. Meningioma: analysis of recurrence and progression following neurosurgical resection. J Neurosurg. 1985;62:18-24.
9. Barbaro NM, Gutin PH, Wilson CB, Sheline GE, Boldrey EB, Wara WM. Radiation therapy in the treatment of partially resected meningiomas. Neurosurgery. 1987;20:525-8.
10. Smith SJ, Boddu S, Macarthur DC. Atypical meningiomas: WHO moved the goalposts? Br J Neurosurg. 2007;21:588-92.
11. Yang SY, Park CK, Park SH, Kim DG, Chung YS, Jung HW. Atypical and anaplastic meningiomas: prognostic implications of clinicopathological features. J Neurol Neurosurg Psychiatry. 2008;79:574-80.
12. Bret P, Gharbi S, Cohadon F, Remond J. Meningioma of the lateral ventricle. 3 recent cases. Neurochirurgie. 1989;35:5-12.
13. Ruttledge MH, Sarrazin J, Rangaratnam S, Phelan CM, Twist E, Merel P, et al. Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomas. Nat Genet. 1994;6:180-4.
14. Mawrin C, Perry A. Pathological classification and molecular genetics of meningiomas. J Neurooncol. 2010;99:379-91.
15. Phillips LE, Koepsell TD, van BG, Kukull WA, Gehrels JA, Longstreth Jr WT. History of head trauma and risk of intracranial meningioma: population-based case-control study. Neurology. 2002;58:1849-52.
16. Preston-Martin S, Pogoda JM, Schlehofer B, Blettner M, Howe GR, Ryan P, et al. An international case-control study of adult glioma and meningioma: the role of head trauma. Int J Epidemiol. 1998;27:579-86.
17. Rossi ML, Cruz SF, Hughes JT, Esiri MM, Coakham HB. Immunocytochemical study of the cellular immune response in meningiomas. J Clin Pathol. 1988;41:314-9.
18. Bo L, Mork SJ, Nyland H. An immunohistochemical study of mononuclear cells in meningiomas. Neuropathol Appl Neurobiol. 1992;18:548-58.
19. Kepes JJ, Chen WY, Connors MH, Vogel FS. "Chordoid" meningeal tumors in young individuals with peritumoral lymphoplasmacellular infiltrates causing systemic manifestations of the Castleman syndrome. A report of seven cases. Cancer. 1988;62:391-406.
20. Rajaraman P, Brenner AV, Neta G, Pfeiffer R, Wang SS, Yeager M, et al. Risk of meningioma and common variation in genes related to innate immunity. Cancer Epidemiol Biomarkers Prev. 2010;19:1356-61.
21. Barnett GH, Chou SM, Bay JW. Posttraumatic intracranial meningioma: a case report and review of the literature. Neurosurgery. 1986;18:75-8.
22. Kunz T, Marklund N, Hillered L, Oliw EH. Cyclooxygenase-2, prostaglandin synthases, and prostaglandin H2 metabolism in traumatic brain injury in the rat. J Neurotrauma. 2002;19:1051-64.
23. Ragel BT, Jensen RL, Couldwell WT. Inflammatory response and meningioma tumorigenesis and the effect of cyclooxygenase-2 inhibitors. Neurosurg Focus. 2007;23:E7.
24. Reszec J, Hermanowicz A, Kochanowicz J, Turek G, Mariak Z, Chyczewski L. Mast cells evaluation in meningioma of various grades. Folia Histochem Cytobiol. 2012;50:542-6.
25. Lolova I, Ivanova A. A histochemical study of meningiomas. Acta Neuropathol. 1972;20:110-21.
26. Popovic EA, Lyons MK, Scheithauer BW, Marsh WR. Mast cell-rich convexity meningioma presenting as chronic subdural hematoma: case report and review of the literature. Surg Neurol. 1994;42:8-13.
27. Tascos NA, Parr J, Gonatas NK. Immunocytochemical study of the glial fibrillary acidic protein in human neoplasms of the central nervous system. Hum Pathol. 1982;13:454-8.
28. Christie KN, Stoward PJ. Endogenous peroxidase in mast cells localized with a semipermeable membrane technique. Histochem J. 1978;10:425-33.
29. Reszec J, Hermanowicz A, Rutkowski R, Bernaczyk P, Mariak Z, Chyczewski L. Evaluation of mast cells and hypoxia inducible factor-1 expression in meningiomas of various grades in correlation with peritumoral brain edema. J Neurooncol. 2013;115:119-25.
30. Jabini R, Moradi A, Afsharnezhad S, Ayatollahi H, Behravan J, Raziee HR, et al. Pathodiagnostic parameters and evaluation of O(6)- methyl guanine methyl transferase gene promoter methylation in meningiomas. Gene. 2014;538:348-53.
31. Gilfillan AM, Austin SJ, Metcalfe DD. Mast cell biology: introduction and overview. Adv Exp Med Biol. 2011;716:2-12.
32. Ribatti D, Crivellato E. Mast cells, angiogenesis, and tumour growth. Biochim Biophys Acta. 1822;2012:2-8.
33. Theoharides TC, Conti P. Mast cells: the JEKYLL and HYDE of tumor growth. Trends Immunol. 2004;25:235-41.
34. Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis and related diseases. New Engl J Med. 2015. in press
35. Theoharides TC, Stewart JM, Panagiotidou S. Mast Cells, Brain Inflammation and Autism. Eur J Pharmacol. 2015. in press
36. Dimitriadou V, Rouleau A, Trung Tuong MD, Newlands GJF, Miller HRP, Luffau G, et al. Functional relationships between sensory nerve fibers and mast cells of dura mater in normal and inflammatory conditions. Neuroscience. 1997;77:829-39.
37. Silver R, Curley JP. Mast cells on the mind: new insights and opportunities. Trends Neurosci. 2013.
38. Theoharides TC, Angelidou A, Alysandratos KD, Zhang B, Asadi S, Francis K, et al. Mast cell activation and autism. Biochim Biophys Acta. 1822;2012:34-41.
39. Theoharides TC. Mast cells: the immune gate to the brain. Life Sci. 1990;46:607-17.
40. Theoharides TC, Konstantinidou A. Corticotropin-releasing hormone and the blood-brain-barrier. Front Biosci. 2007;12:1615-28.
41. Esposito P, Chandler N, Kandere-Grzybowska K, Basu S, Jacobson S, Connolly R, et al. Corticotropin-releasing hormone (CRH) and brain mast cells regulate blood-brain-barrier permeability induced by acute stress. J Pharmacol Exp Ther. 2002;303:1061-6.
42. Theoharides TC, Kalogeromitros D. The critical role of mast cell in allergy and inflammation. Ann NY Acad Sci. 2006;1088:78-99.
43. Ribatti D. The crucial role of mast cells in blood-brain barrier alterations. Exp Cell Res. 2015.
44. Nelissen S, Lemmens E, Geurts N, Kramer P, Maurer M, Hendriks J, et al. The role of mast cells in neuroinflammation. Acta Neuropathol. 2013;125:637-50.
45. Skaper SD, Facci L, Giusti P. Mast cells, glia and neuroinflammation: partners in crime? Immunology. 2014;141:314-27.
46. Theoharides TC, Zhang B. Neuro-Inflammation, blood-brain barrier, seizures and autism. J Neuroinflammation. 2011;8:168.
47. Skaper SD, Facci L, Giusti P. Mast cells, glia and neuroinflammation: partners in crime? Immunology. 2014;141:314-27.
48. Theoharides TC, Donelan J, Kandere-Grzybowska K, Konstantinidou A. The role of mast cells in migraine pathophysiology. Brain Res Rev. 2005;49:65-76.
49. Theoharides TC, Asadi S, Patel A. Focal brain inflammation and autism. J Neuroinflammation. 2013;10:46.
50. Vasiadi M, Newman J, Theoharides TC. Isoflavones inhibit poly(I:C)-induced serum, brain, and skin inflammatory mediators - relevance to chronic fatigue syndrome. J Neuroinflammation. 2014;11:168.
51. Hoogland IC, Houbolt C, van Westerloo DJ, van Gool WA, van de BD. Systemic inflammation and microglial activation: systematic review of animal experiments. J Neuroinflammation. 2015;12:114.
52. Ribatti D. Mast cells as therapeutic target in cancer. Eur J Pharmacol. 2015
53. Polajeva J, Sjosten AM, Lager N, Kastemar M, Waern I, Alafuzoff I, et al. Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12. PLoS ONE. 2011;6:e25222.
54. Polajeva J, Bergstrom T, Edqvist PH, Lundequist A, Sjosten A, Nilsson G, et al. Glioma-derived macrophage migration inhibitory factor (MIF) promotes mast cell recruitment in a STAT5-dependent manner. Mol Oncol. 2014;8:50-8.
55. Kumar P, Kumar S, Marsden HB, Lynch PG, Earnshaw E. Weibel-Palade bodies in endothelial cells as a marker for angiogenesis in brain tumors. Cancer Res. 1980;40:2010-9.
56. Tachibana O, Yamashima T, Yamashita J. Immunohistochemical study of erythropoietin in cerebellar hemangioblastomas associated with secondary polycythemia. Neurosurgery. 1991;28:24-6.
57. Theoharides TC, Rozniecki JJ, Sahagian G, Kempuraj D, Kalogeromitros D, Conti P. Impact of stress and mast cells on brain metastases. J Neuroimmunol. 2008;205:1-7.
58. Esposito P, Jacobson S, Connolly R, Gheorghe D, Theoharides TC. Non-invasive assessment of blood-brain barrier (BBB) permeability using a gamma camera to detect 99Technetium-gluceptate extravasation in rat brain. Brain Res Protocols. 2001;8:143-9.
59. Rozniecki JJ, Sahagian GG, Kempuraj D, Tao K, Jocobson S, Zhang B, et al. Brain metastases of mouse mammary adenocarcinoma is increased by acute stress. Brain Res. 2010;1366:204-10.
60. Sayegh ET, Henderson GA, Burch EA, Reis GF, Cha S, Oh T, et al. Intrameningioma metastasis of breast carcinoma. Rare Tumors. 2014;6:5313.
61. Okada E, Nakamura M, Koshida Y, Mukai K, Toyama Y, Matsumoto M. Breast carcinoma metastasis to meningioma in the thoracic spine: a case report and review of the literature. J Spinal Cord Med. 2015;38:231-5.
62. Milano MT, Grossman CE. Meningioma in breast cancer patients: population-based analysis of clinicopathologic characteristics. Am J Clin Oncol. 2014
63. Theoharides TC. Mast cells and pancreatic cancer. N Engl J Med. 2008;358:1860-1.
64. Jensen RL. Brain tumor hypoxia: tumorigenesis, angiogenesis, imaging, pseudoprogression, and as a therapeutic target. J Neurooncol. 2009;92:317-35.
65. Kazner E, Lanksch W, Steinhoff H, Wilske J. Computerized axial tomography of the skull - diagnostic possibilities and clinical results (author's transl). Fortschr Neurol Psychiatr Grenzgeb. 1975;43:487-574.
66. Tirakotai W, Mennel HD, Celik I, Hellwig D, Bertalanffy H, Riegel T. Secretory meningioma: immunohistochemical findings and evaluation of mast cell infiltration. Neurosurg Rev. 2006;29:41-8.
67. Epari S, Sharma MC, Sarkar C, Garg A, Gupta A, Mehta VS. Chordoid meningioma, an uncommon variant of meningioma: a clinicopathologic study of 12 cases. J Neurooncol. 2006;78:263-9.
68. Tena-Suck ML, Collado-Ortiz MA, Salinas-Lara C, Garcia-Lopez R, Gelista N, Rembao-Bojorquez D. Chordoid meningioma: a report of ten cases. J Neurooncol. 2010;99:41-8.
69. Schober R, Himuro H, Wechsler W. Cystic changes and vascular permeability in meningiomas. Clin Neuropathol. 1988;7:16-21.
70. Karamitopoulou E, Shoni M, Theoharides TC. Increased number of non-degranulated mast cells in pancreatic ductal adenocarcinoma but not in acute pancreatitis. Int J Immunopathol Pharmacol. 2014;27:213-20.
71. Abe T, Black PM, Ojemann RG, Hedley-White ET. Cerebral edema in intracranial meningiomas: evidence for local and diffuse patterns and factors associated with its occurrence. Surg Neurol. 1994;42:471-5.
72. Buhl R, Hugo HH, Mehdorn HM. Brain oedema in secretory meningiomas. J Clin Neurosci. 2001;8 Suppl 1:19-21.
73. Wick W, Kuker W. Brain edema in neurooncology: radiological assessment and management. Onkologie. 2004;27:261-6.
74. Nakano T, Asano K, Miura H, Itoh S, Suzuki S. Meningiomas with brain edema: radiological characteristics on MRI and review of the literature. Clin Imaging. 2002;26:243-9.
75. Machein MR, Plate KH. VEGF in brain tumors. J Neurooncol. 2000;50:109-20.
76. Nassehi D. Intracranial meningiomas, the VEGF-A pathway, and peritumoral brain oedema. Dan Med J. 2013;60:B4626.
77. Hou J, Kshettry VR, Selman WR, Bambakidis NC. Peritumoral brain edema in intracranial meningiomas: the emergence of vascular endothelial growth factor-directed therapy. Neurosurg Focus. 2013;35:E2.
78. Cao J, Papadopoulou N, Kempuraj D, Boucher WS, Sugimoto K, Cetrulo CL, et al. Human mast cells express corticotropin-releasing hormone (CRH) receptors and CRH leads to selective secretion of vascular endothelial growth factor. J Immunol. 2005;174:7665-75.
79. Kempuraj D, Papadopoulou NG, Lytinas M, Huang M, Kandere-Grzybowska K, Madhappan B, et al. Corticotropin-releasing hormone and its structurally related urocortin are synthesized and secreted by human mast cells. Endocrinology. 2004;145:43-8.
80. Shahani S, Nudelman RJ, Nalini R, Kim HS, Samson SL. Ectopic corticotropin-releasing hormone (CRH) syndrome from metastatic small cell carcinoma: a case report and review of the literature. Diagn Pathol. 2010;5:56.
81. Feoktistov A, Diamond M. Diagnosing and understanding adult headache. Otolaryngol Clin North Am. 2014;47:175-85.
82. Smith RM, Robertson CE, Garza I. Orthostatic headache from supratentorial meningioma. Cephalalgia. 2015
83. Heron A, Dubayle D. A focus on mast cells and pain. J Neuroimmunol. 2013;264:1-7.
84. Hancock BW, Dandona P, Cumberland DC, Jarratt JA. Systemic mastocytosis--central nervous system features and lymphographic demonstration of lymph node involvement. Postgrad Med J. 1976;52:659-62.
85. Ransohoff RM. Immunology: barrier to electrical storms. Nature. 2009;457:155-6.
86. Pehlivanidis C, Fotoulaki M, Boucher W, Kempuraj D, Pang X, Konstantinidou A, et al. Acute stress-induced seizures and loss of consciousness in a ten-year-old boy with cutaneous mastocytosis. J Clin Psychopharmacol. 2002;22:221-4.
87. Karagkouni A, Alevizos M, Theoharides TC. Effect of stress on brain inflammation and multiple sclerosis. Autoimmun Rev. 2013;12:947-53.
88. Bradstreet JJ, Pacini S, Ruggiero M. A new methodology of viewing extra-axial fluid and cortical abnormalities in children with autism via transcranial ultrasonography. Front Hum Neurosci. 2014;7:934.
89. Theoharides TC, Stewart JM, Hatziagelaki E, Kolaitis G. Brain "fog," inflammation and obesity: key aspects of 2 neuropsychiatric disorders improved by luteolin. Front. Neurosci. 2015. in press
90. Roth P, Regli L, Tonder M, Weller M. Tumor-associated edema in brain cancer patients: pathogenesis and management. Expert Rev Anticancer Ther. 2013;13:1319-25.
91. Temel SG, Kahveci Z. Cyclooxygenase-2 expression in astrocytes and microglia in human oligodendroglioma and astrocytoma. J Mol Histol. 2009;40:369-77.
92. Xiao X, Shi D, Liu L, Wang J, Xie X, Kang T, et al. Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling. PLoS ONE. 2011;6:e22934.
93. de Pascual-Teresa S, Johnston KL, DuPont MS, O'Leary KA, Needs PW, Morgan LM, et al. Quercetin metabolites downregulate cyclooxygenase-2 transcription in human lymphocytes ex vivo but not in vivo. J Nutr. 2004;134:552-7.
94. Lamy S, Moldovan PL, Ben SA, Annabi B. Biphasic effects of luteolin on interleukin-1beta-induced cyclooxygenase-2 expression in glioblastoma cells. Biochim Biophys Acta. 1853;2015:126-35.
95. Piantelli M, Rinelli A, Macri E, Maggiano N, Larocca LM, Scerrati M, et al. Type II estrogen binding sites and antiproliferative activity of quercetin in human meningiomas. Cancer. 1993;71:193-8.
96. Park MH, Min dS. Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells. Biochem Biophys Res Commun. 2011;412:710-5.
97. Braganhol E, Zamin LL, Canedo AD, Horn F, Tamajusuku AS, Wink MR, et al. Antiproliferative effect of quercetin in the human U138MG glioma cell line. Anticancer Drugs. 2006;17:663-71.
98. Jeon YW, Suh YJ. Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells. Oncol Rep. 2013;29:819-25.
99. Kempuraj D, Madhappan B, Christodoulou S, Boucher W, Cao J, Papadopoulou N, et al. Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells. Br J Pharmacol. 2005;145:934-44.
100. Kimata M, Shichijo M, Miura T, Serizawa I, Inagaki N, Nagai H. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin Exp Allergy. 2000;30:501-8.
101. Asadi S, Zhang B, Weng Z, Angelidou A, Kempuraj D, Alysandratos KD, et al. Luteolin and thiosalicylate inhibit HgCl(2) and thimerosal-induced VEGF release from human mast cells. Int J Immunopathol Pharmacol. 2010;23:1015-20.
102. Kempuraj D, Tagen M, Iliopoulou BP, Clemons A, Vasiadi M, Boucher W, et al. Luteolin inhibits myelin basic protein-induced human mast cell activation and mast cell dependent stimulation of Jurkat T cells. Br J Pharmacol. 2008;155:1076-84.
103. Verbeek R, Plomp AC, van Tol EA, van Noort JM. The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and interferon-gamma production by murine and human autoimmune T cells. Biochem Pharmacol. 2004;68:621-9.
104. Shim SY, Park JR, Byun DS. 6-Methoxyluteolin from Chrysanthemum zawadskii var. latilobum suppresses histamine release and calcium influx via down-regulation of FcepsilonRI alpha chain expression. J Microbiol Biotechnol. 2012;22:622-7.
105. Weng Z, Patel A, Panagiotidou S, Theoharidess TC. The novel flavone tetramethoxyluteolin is a potent inhibitor of human mast cells. J Allergy Clin Immunol. 2014;14:1044-52.
106. Jang S, Kelley KW, Johnson RW. Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proc Natl Acad Sci U S A. 2008;105:7534-9.
107. Dirscherl K, Karlstetter M, Ebert S, Kraus D, Hlawatsch J, Walczak Y, et al. Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype. J Neuroinflammation. 2010;7:3.
108. Chen HQ, Jin ZY, Wang XJ, Xu XM, Deng L, Zhao JW. Luteolin protects dopaminergic neurons from inflammation-induced injury through inhibition of microglial activation. Neurosci Lett. 2008;448:175-9.
109. Kao TK, Ou YC, Lin SY, Pan HC, Song PJ, Raung SL, et al. Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia. J Nutr Biochem. 2011;22:612-24.
110. Gupta S, Ellis SE, Ashar FN, Moes A, Bader JS, Zhan J, et al. Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat Commun. 2014;5:5748.
111. Theoharides TC, Asadi S, Panagiotidou S. A case series of a luteolin formulation (NeuroProtek(R)) in children with autism spectrum disorders. Int J Immunopathol Pharmacol. 2012;25:317-23.
112. Taliou A, Zintzaras E, Lykouras L, Francis K. An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders. Clin Ther. 2013;35:592-602.
113. Beauchamp GK, Keast RS, Morel D, Lin J, Pika J, Han Q, et al. Phytochemistry: ibuprofen-like activity in extra-virgin olive oil. Nature. 2005;437:45-6.
114. Middleton EJ, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacol Rev. 2000;52:673-751.
115. Jager AK, Saaby L. Flavonoids and the CNS. Molecules. 2011;16:1471-85.
116. Grosso C, Valentao P, Ferreres F, Andrade PB. The use of flavonoids in central nervous system disorders. Curr Med Chem. 2013;20:4697-719.
117. Solanki I, Parihar P, Mansuri ML, Parihar MS. Flavonoid-based therapies in the early management of neurodegenerative diseases. Adv Nutr. 2015;6:64-72.
118. Jones QR, Warford J, Rupasinghe HP, Robertson GS. Target-based selection of flavonoids for neurodegenerative disorders. Trends Pharmacol Sci. 2012;33:602-10.
119. Theoharides TC, Stewart JM, Hatziagelaki E, Kolaitis G. Brain "fog", inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin. Front Neurosci. 2015;9:225.