Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2014

Open Access 01-12-2014 | Research

Isoflavones inhibit poly(I:C)-induced serum, brain, and skin inflammatory mediators - relevance to chronic fatigue syndrome

Authors: Magdalini Vasiadi, Jennifer Newman, Theoharis C Theoharides

Published in: Journal of Neuroinflammation | Issue 1/2014

Login to get access

Abstract

Background

Chronic Fatigue Syndrome (CFS) is a neuroimmunoendocrine disease affecting about 1% of the US population, mostly women. It is characterized by debilitating fatigue for six or more months in the absence of cancer or other systemic diseases. Many CFS patients also have fibromyalgia and skin hypersensitivity that worsen with stress. Corticotropin-releasing hormone (CRH) and neurotensin (NT), secreted under stress, activate mast cells (MC) necessary for allergic reactions to release inflammatory mediators that could contribute to CFS symptoms.

Objective

To investigate the effect of isoflavones on the action of polyinosinic:polycytidylic acid (poly(I:C)), with or without swim stress, on mouse locomotor activity and inflammatory mediator expression, as well as on human MC activation.

Methods

Female C57BL/6 mice were randomly divided into four groups: (a) control/no-swim, (b) control/swim, (c) polyinosinic:polycytidylic acid (poly(I:C))/no swim, and (d) polyinosinic:polycytidylic acid (poly(I:C))/swim. Mice were provided with chow low or high in isoflavones for 2 weeks prior to ip injection with 20 mg/kg poly(I:C) followed or not by swim stress for 15 minutes. Locomotor activity was monitored overnight and animals were sacrificed the following day. Brain and skin gene expression, as well as serum levels, of inflammatory mediators were measured. Data were analyzed using the non-parametric Mann-Whitney U-test.

Results

Poly(I:C)-treated mice had decreased locomotor activity over 24 hours, and increased serum levels of TNF-α, IL-6, KC (IL-8/CXCL8 murine homolog), CCL2,3,4,5, CXCL10, as well as brain and skin gene expression of TNF, IL-6, KC (Cxcl1, IL8 murine homolog), CCL2, CCL4, CCL5 and CXCL10. Histidine decarboxylase (HDC) and NT expression were also increased, but only in the skin, over the same period. High isoflavone diet reversed these effects.

Conclusion

Poly(I:C) treatment decreased mouse locomotor activity and increased serum levels and brain and skin gene expression of inflammatory mediators. These effects were inhibited by isoflavones that may prove useful in CFS.
Appendix
Available only for authorised users
Literature
1.
Jason LA, Corradi K, Torres-Harding S, Taylor RR, King C: Chronic fatigue syndrome: the need for subtypes. Neuropsychol Rev. 2005, 15: 29-58.PubMed
2.
Jahan F, Nanji K, Qidwai W, Qasim R: Fibromyalgia syndrome: an overview of pathophysiology, diagnosis and management. Oman Med J. 2012, 27: 192-195.PubMedCentralPubMed
3.
Anderson VR, Jason LA, Hlavaty LE, Porter N, Cudia J: A review and meta-synthesis of qualitative studies on myalgic encephalomyelitis/chronic fatigue syndrome. Patient Educ Couns. 2012, 86: 147-155.PubMedCentralPubMed
4.
Van't LM, Zielhuis GA, van der Meer JW, Verbeek AL, Bleijenberg G: Fatigue and chronic fatigue syndrome-like complaints in the general population. Eur J Public Health. 2010, 20: 251-257.
5.
Griffith JP, Zarrouf FA: A systematic review of chronic fatigue syndrome: don't assume it's depression. Prim Care Companion J Clin Psychiatry. 2008, 10: 120-128.PubMedCentralPubMed
6.
Holgate ST, Komaroff AL, Mangan D, Wessely S: Chronic fatigue syndrome: understanding a complex illness. Nat Rev Neurosci. 2011, 12: 539-544.PubMed
7.
Katz BZ, Shiraishi Y, Mears CJ, Binns HJ, Taylor R: Chronic fatigue syndrome after infectious mononucleosis in adolescents. Pediatrics. 2009, 124: 189-193.PubMedCentralPubMed
8.
Fremont M, Metzger K, Rady H, Hulstaert J, De MK: Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients. In Vivo. 2009, 23: 209-213.PubMed
9.
Theoharides TC: Atopic conditions in search of pathogenesis and therapy. Clin Ther. 2013, 35: 544-547.PubMed
10.
Martinez-Martinez LA, Mora T, Vargas A, Fuentes-Iniestra M, Martinez-Lavin M: Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: a review of case-control studies. J Clin Rheumatol. 2014, 20: 146-150.PubMed
11.
Aaron LA, Buchwald D: Fibromyalgia and other unexplained clinical conditions. Curr Rheumatol. 2001, 3: 116-122.
12.
Abbi B, Natelson BH: Is chronic fatigue syndrome the same illness as fibromyalgia: evaluating the 'single syndrome' hypothesis. QJM. 2013, 106: 3-9.PubMedCentralPubMed
13.
Aaron LA, Buchwald D: Chronic diffuse musculoskeletal pain, fibromyalgia and co-morbid unexplained clinical conditions. Best Prac Res Clin Rheumatol. 2003, 17: 563-574.
14.
Smith MS, Martin-Herz SP, Womack WM, Marsigan JL: Comparative study of anxiety, depression, somatization, functional disability, and illness attribution in adolescents with chronic fatigue or migraine. Pediatrics. 2003, 111: e376-e381.PubMed
15.
Theoharides TC, Cochrane DE: Critical role of mast cells in inflammatory diseases and the effect of acute stress. J Neuroimmunol. 2004, 146: 1-12.PubMed
16.
Gur A, Oktayoglu P: Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment. Curr Pharm Des. 2008, 14: 1274-1294.PubMed
17.
Cleare AJ, Miell J, Heap E, Sookdeo S, Young L, Malhi GS, O'Keane V: Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy. J Clin Endocrinol Metab. 2001, 86: 3545-3554.PubMed
18.
Crawley E, Hunt L, Stallard P: Anxiety in children with CFS/ME. Eur Child Adolesc Psychiatry. 2009, 18: 683-689.PubMed
19.
Theoharides TC, Weinkauf C, Conti P: Brain cytokines and neuropsychiatric disorders. J Clin Psychopharmacol. 2004, 24: 577-581.PubMed
20.
Maes M, Twisk FN, Ringel K: Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression. Psychother Psychosom. 2012, 81: 286-295.PubMed
21.
Pae CU, Marks DM, Patkar AA, Masand PS, Luyten P, Serretti A: Pharmacological treatment of chronic fatigue syndrome: focusing on the role of antidepressants. Expert Opin Pharmacother. 2009, 10: 1561-1570.PubMed
22.
Huang L, Frampton G, Rao A, Zhang KS, Chen W, Lai JM, Yin XY, Walker K, Culbreath B, Leyva-Illades D, Quinn M, McMillin M, Bradley M, Liang LJ, DeMorrow S: Monoamine oxidase A expression is suppressed in human cholangiocarcinoma via coordinated epigenetic and IL-6-driven events. Lab Invest. 2012, 92: 1451-1460.PubMedCentralPubMed
23.
Bansal AS, Bradley AS, Bishop KN, Kiani-Alikhan S, Ford B: Chronic fatigue syndrome, the immune system and viral infection. Brain Behav Immun. 2012, 26: 24-31.PubMed
24.
Dietert RR, Dietert JM: Possible role for early-life immune insult including developmental immunotoxicity in chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME). Toxicology. 2008, 247: 61-72.PubMed
25.
Bower JE: Fatigue, brain, behavior, and immunity: summary of the 2012 Named Series on fatigue. Brain Behav Immun. 2012, 26: 1220-1223.PubMed
26.
Klimas NG, Broderick G, Fletcher MA: Biomarkers for chronic fatigue. Brain Behav Immun. 2012, 26: 1202-1210.PubMed
27.
Blanco I, Beritze N, Arguelles M, Carcaba V, Fernandez F, Janciauskiene S, Oikonomopoulou K, De Serres FJ, Fernandez-Bustillo E, Hollenberg MD: Abnormal overexpression of mastocytes in skin biopsies of fibromyalgia patients. Clin Rheumatol. 2010, 29: 1403-1412.PubMed
28.
Enestrom S, Bengtsson A, Frodin T: Dermal IgG deposits and increase of mast cells in patients with fibromyalgia-relevant findings or epiphenomena?. Scand J Rheumatol. 1997, 26: 308-313.PubMed
29.
Steinberg P, Pheley A, Peterson PK: Influence of immediate hypersensitivity skin reactions on delayed reactions in patients with chronic fatigue syndrome. J Allergy Clin Immunol. 1996, 98: 1126-1128.PubMed
30.
Yener M, Erturan I, Ceyhan AM, Inal EE, Kozanoglu OO: The evaluation of prevalence of fibromyalgia in patients with chronic urticaria. Med Sci Monit. 2013, 19: 757-761.PubMedCentralPubMed
31.
Nijs J, De BP, De MK, Demanet C, Vincken W, Schuermans D, McGregor N: Associations between bronchial hyperresponsiveness and immune cell parameters in patients with chronic fatigue syndrome. Chest. 2003, 123: 998-1007.PubMed
32.
Theoharides TC, Papaliodis D, Tagen M, Konstantinidou A, Kempuraj D, Clemons A: Chronic fatigue syndrome, mast cells, and tricyclic antidepressants. J Clin Psychopharmacol. 2005, 25: 515-520.PubMed
33.
Theoharides TC, Donelan JM, Papadopoulou N, Cao J, Kempuraj D, Conti P: Mast cells as targets of corticotropin-releasing factor and related peptides. Trends Pharmacol Sci. 2004, 25: 563-568.PubMed
34.
Paus R, Theoharides TC, Arck PC: Neuroimmunoendocrine circuitry of the 'brain-skin connection'. Trends Immunol. 2006, 27: 32-39.PubMed
35.
Theoharides TC, Konstantinidou A: Corticotropin-releasing hormone and the blood-brain-barrier. Front Biosci. 2007, 12: 1615-1628.PubMed
36.
Rozniecki JJ, Dimitriadou V, Lambracht-Hall M, Pang X, Theoharides TC: Morphological and functional demonstration of rat dura mast cell-neuron interactions in vitro and in vivo. Brain Res. 1999, 849: 1-15.PubMed
37.
Dimitriadou V, Rouleau A, Trung Tuong MD, Newlands GJF, Miller HRP, Luffau G, Schwartz J-C, Garbarg M: Functional relationships between sensory nerve fibers and mast cells of dura mater in normal and inflammatory conditions. Neuroscience. 1997, 77: 829-839.PubMed
38.
Theoharides TC, Spanos CP, Pang X, Alferes L, Ligris K, Letourneau R, Rozniecki JJ, Webster E, Chrousos G: Stress-induced intracranial mast cell degranulation. A corticotropin releasing hormone-mediated effect. Endocrinology. 1995, 136: 5745-5750.PubMed
39.
Donelan J, Boucher W, Papadopoulou N, Lytinas M, Papaliodis D, Theoharides TC: Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process. Proc Natl Acad Sci U S A. 2006, 103: 7759-7764.PubMedCentralPubMed
40.
Nicot A, Rowe WB, De Kloet ER, Betancur C, Jessop DS, Lightman SL, Quirion R, Rostene W, Berod A: Endogenous neurotensin regulates hypothalamic-pituitary-adrenal axis activity and peptidergic neurons in the rat hypothalamic paraventricular nucleus. J Neuroendocrinol. 1997, 9: 263-269.PubMed
41.
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.PubMed
42.
Kempuraj D, Madhappan B, Christodoulou S, Boucher W, Cao J, Papadopoulou N, Cetrulo CL, Theoharides TC: Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells. Br J Pharmacol. 2005, 145: 934-944.PubMedCentralPubMed
43.
Miranda CL, Maier CS, Stevens JF: Flavonoids. Chichester: eLS. John Wiley & Sons, Ltd; 2012. doi:10. 1002/9780470015902. a0003068. pub2.
44.
Uceyler N, Hauser W, Sommer C: Systematic review with meta-analysis: cytokines in fibromyalgia syndrome. BMC Musculoskelet Disord. 2011, 12: 245.PubMedCentralPubMed
45.
Abbott NJ: Inflammatory mediators and modulation of blood-brain barrier permeability. Cell Mol Neurobiol. 2000, 20: 131-147.PubMed
46.
Cocchiara R, Bongiovanni A, Albeggiani G, Azzolina A, Geraci D: Evidence that brain mast cells can modulate neuroinflammatory responses by tumor necrosis factor-α production. Neuroreport. 1998, 9: 95-98.PubMed
47.
Probert L, Akassoglou K, Kassiotis G, Pasparakis M, Alexopoulou L, Kollias G: TNF-α transgenic and knockout models of CNS inflammation and degeneration. J Neuroimmunol. 1997, 72: 137-141.PubMed
48.
Bachelet I, Levi-Schaffer F: Mast cells as effector cells: a co-stimulating question. Trends Immunol. 2007, 28: 360-365.PubMed
49.
Salamon P, Shoham NG, Gavrieli R, Wolach B, Mekori YA: Human mast cells release interleukin-8 and induce neutrophil chemotaxis on contact with activated T cells. Allergy. 2005, 60: 1316-1319.PubMed
50.
Nakae S, Suto H, Iikura M, Kakurai M, Sedgwick JD, Tsai M, Galli SJ: Mast cells enhance T cell activation: importance of mast cell costimulatory molecules and secreted TNF. J Immunol. 2006, 176: 2238-2248.PubMed
51.
Kempuraj D, Tagen M, Iliopoulou BP, Clemons A, Vasiadi M, Boucher W, House M, Wolferg A, Theoharides TC: Luteolin inhibits myelin basic protein-induced human mast cell activation and mast cell dependent stimulation of Jurkat T cells. Br J Pharmacol. 2008, 155: 1076-1084.PubMedCentralPubMed
52.
Sachdeva AK, Kuhad A, Tiwari V, Arora V, Chopra K: Protective effect of epigallocatechin gallate in murine water-immersion stress model of chronic fatigue syndrome. Basic Clin Pharmacol Toxicol. 2010, 2010: 2010.
53.
Sachdeva AK, Kuhad A, Tiwari V, Chopra K: Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence. Behav Brain Res. 2009, 205: 414-420.PubMed
54.
Vij G, Gupta A, Chopra K: Modulation of antigen-induced chronic fatigue in mouse model of water immersion stress by naringin, a polyphenolic antioxidant. Fundam Clin Pharmacol. 2009, 23: 331-337.PubMed
55.
Gupta A, Vij G, Sharma S, Tirkey N, Rishi P, Chopra K: Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model. Immunobiology. 2009, 214: 33-39.PubMed
56.
Sachdeva AK, Kuhad A, Chopra K: Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome. Brain Res Bull. 2011, 86: 165-172.PubMed
57.
Ottenweller JE, Natelson BH, Gause WC, Carroll KK, Beldowicz D, Zhou XD, LaManca JJ: Mouse running activity is lowered by Brucella abortus treatment: a potential model to study chronic fatigue. Physiol Behav. 1998, 63: 795-801.PubMed
58.
Surapaneni DK, Adapa SR, Preeti K, Teja GR, Veeraragavan M, Krishnamurthy S: Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats. J Ethnopharmacol. 2012, 143: 91-99.PubMed
59.
Moser B, Wolf M, Walz A, Loetscher P: Chemokines: multiple levels of leukocyte migration control. Trends Immunol. 2004, 25: 75-84.PubMed
60.
Charo IF, Ransohoff RM: The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006, 354: 610-621.PubMed
61.
Koelink PJ, Overbeek SA, Braber S, De KP, Folkerts G, Smit MJ, Kraneveld AD: Targeting chemokine receptors in chronic inflammatory diseases: an extensive review. Pharmacol Ther. 2012, 133: 1-18.PubMed
62.
Juremalm M, Nilsson G: Chemokine receptor expression by mast cells. Chem Immunol Allergy. 2005, 87: 130-144.PubMed
63.
Oliveira SH, Lukacs NW: Stem cell factor and IgE-stimulated murine mast cells produce chemokines (CCL2, CCL17, CCL22) and express chemokine receptors. Inflamm Res. 2001, 50: 168-174.PubMed
64.
65.
Matsushima H, Yamada N, Matsue H, Shimada S: TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells. J Immunol. 2004, 173: 531-541.PubMed
66.
Orinska Z, Bulanova E, Budagian V, Metz M, Maurer M, Bulfone-Paus S: TLR3-induced activation of mast cells modulates CD8+ T-cell recruitment. Blood. 2005, 106: 978-987.PubMed
67.
Ott VL, Cambier JC, Kappler J, Marrack P, Swanson BJ: Mast cell-dependent migration of effector CD8+ T cells through production of leukotriene B4. Nat Immunol. 2003, 4: 974-981.PubMed
68.
Akira S, Takeda K, Kaisho T: Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol. 2001, 2: 675-680.PubMed
69.
Aderem A, Ulevitch RJ: Toll-like receptors in the induction of the innate immune response. Nature. 2000, 406: 782-787.PubMed
70.
Okayama Y: Mast cell-derived cytokine expression induced via Fc receptors and Toll-like receptors. Chem Immunol Allergy. 2005, 87: 101-110.PubMed
71.
Vercammen E, Staal J, Beyaert R: Sensing of viral infection and activation of innate immunity by toll-like receptor 3. Clin Microbiol Rev. 2008, 21: 13-25.PubMedCentralPubMed
72.
Saluja R, Delin I, Nilsson GP, Adner M: FcepsilonR1-mediated mast cell reactivity is amplified through prolonged Toll-like receptor-ligand treatment. PLoS One. 2012, 7: e43547.PubMedCentralPubMed
73.
Kulka M, Alexopoulou L, Flavell RA, Metcalfe DD: Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J Allergy Clin Immunol. 2004, 114: 174-182.PubMed
74.
Lappalainen J, Rintahaka J, Kovanen PT, Matikainen S, Eklund KK: Intracellular RNA recognition pathway activates strong anti-viral response in human mast cells. Clin Exp Immunol. 2013, 172: 121-128.PubMedCentralPubMed
75.
Huang Z, Mochizuki T, Watanabe H, Kagoshima M, Maeyama K: Biphasic evaluation of plasma histamine induced by water immersion stress, and their sources in rats. Eur J Pharmacol. 1998, 360: 139-146.PubMed
76.
Huang M, Berry J, Kandere K, Lytinas M, Karalis K, Theoharides TC: Mast cell deficient W/Wv mice lack stress-induced increase in serum IL-6 levels, as well as in peripheral CRH and vascular permeability, a model of rheumatoid arthritis. Intl J Immunopathol Pharmacol. 2002, 15: 249-254.
77.
Ding W, Liu Y: Genistein attenuates genioglossus muscle fatigue under chronic intermittent hypoxia by down-regulation of oxidative stress level and up-regulation of antioxidant enzyme activity through ERK1/2 signaling pathway. Oral Dis. 2011, 17: 677-684.PubMed
78.
Jia Z, Zhen W, Velayutham Anandh BP, Liu D: Phytoestrogen genistein protects against endothelial barrier dysfunction in vascular endothelial cells through PKA-mediated suppression of RhoA signaling. Endocrinology. 2013, 154: 727-737.PubMedCentralPubMed
79.
Ji G, Zhang Y, Yang Q, Cheng S, Hao J, Zhao X, Jiang Z: Genistein suppresses LPS-induced inflammatory response through inhibiting NF-kappaB following AMP kinase activation in RAW 264.7 macrophages. PLoS One. 2012, 7: e53101.PubMedCentralPubMed
80.
Yamashita S, Tsukamoto S, Kumazoe M, Kim YH, Yamada K, Tachibana H: Isoflavones suppress the expression of the FcepsilonRI high-affinity immunoglobulin E receptor independent of the estrogen receptor. J Agric Food Chem. 2012, 60: 8379-8385.PubMed
81.
Kuo YH, Tsai WJ, Loke SH, Wu TS, Chiou WF: Astragalus membranaceus flavonoids (AMF) ameliorate chronic fatigue syndrome induced by food intake restriction plus forced swimming. J Ethnopharmacol. 2009, 122: 28-34.PubMed
82.
Gupta A, Vij G, Chopra K: Possible role of oxidative stress and immunological activation in mouse model of chronic fatigue syndrome and its attenuation by olive extract. J Neuroimmunol. 2010, 226 (1-2): 3-7.PubMed
83.
Shaulian E, Karin M: AP-1 as a regulator of cell life and death. Nat Cell Biol. 2002, 4: E131-E136.PubMed
84.
Hess J, Angel P, Schorpp-Kistner M: AP-1 subunits: quarrel and harmony among siblings. J Cell Sci. 2004, 117: 5965-5973.PubMed
85.
Fraga CG, Oteiza PI: Dietary flavonoids: role of (-)-epicatechin and related procyanidins in cell signaling. Free Radic Biol Med. 2011, 51: 813-823.PubMed
86.
Surh YJ, Kundu JK, Na HK: Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med. 2008, 74: 1526-1539.PubMed
87.
Yang Y, Oh JM, Heo P, Shin JY, Kong B, Shin J, Lee JC, Oh JS, Park KW, Lee CH, Shin YK, Kweon DH: Polyphenols differentially inhibit degranulation of distinct subsets of vesicles in mast cells by specific interaction with granule-type-dependent SNARE complexes. Biochem J. 2013, 450: 537-546.PubMed
88.
Macready AL, Kennedy OB, Ellis JA, Williams CM, Spencer JP, Butler LT: Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies. Genes Nutr. 2009, 4: 227-242.PubMedCentralPubMed
89.
Casini ML, Marelli G, Papaleo E, Ferrari A, D'Ambrosio F, Unfer V: Psychological assessment of the effects of treatment with phytoestrogens on postmenopausal women: a randomized, double-blind, crossover, placebo-controlled study. Fertil Steril. 2006, 85: 972-978.PubMed
90.
Duffy R, Wiseman H, File SE: Improved cognitive function in postmenopausal women after 12 weeks of consumption of a soya extract containing isoflavones. Pharmacol Biochem Behav. 2003, 75: 721-729.PubMed
91.
Davis JM, Murphy EA, Carmichael MD, Davis B: Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol. 2009, 296: R1071-R1077.PubMed
92.
Youdim KA, Qaiser MZ, Begley DJ, Rice-Evans CA, Abbott NJ: Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med. 2004, 36: 592-604.PubMed
93.
Ishisaka A, Ichikawa S, Sakakibara H, Piskula MK, Nakamura T, Kato Y, Ito M, Miyamoto K, Tsuji A, Kawai Y, Terao J: Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats. Free Radic Biol Med. 2011, 51: 1329-1336.PubMed
94.
Inoue T, Suzuki Y, Ra C: Epigallocatechin-3-gallate inhibits mast cell degranulation, leukotriene C4 secretion, and calcium influx via mitochondrial calcium dysfunction. Free Radic Biol Med. 2010, 49: 632-640.PubMed
95.
Park HH, Lee S, Son HY, Park SB, Kim MS, Choi EJ, Singh TS, Ha JH, Lee MG, Kim JE, Hyun MC, Kwon TK, Kim YH, Kim SH: Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells. Arch Pharm Res. 2008, 31: 1303-1311.PubMed
96.
Shin HY, Kim SH, Jeong HJ, Kim SY, Shin TY, Um JY, Hong SH, Kim HM: Epigallocatechin-3-gallate inhibits secretion of TNF-alpha, IL-6 and IL-8 through the attenuation of ERK and NF-kappaB in HMC-1 cells. Int Arch Allergy Immunol. 2007, 142: 335-344.PubMed
97.
Kumar A, Goyal R: Quercetin protects against acute immobilization stress-induced behaviors and biochemical alterations in mice. J Med Food. 2008, 11: 469-473.PubMed
98.
Asadi S, Zhang B, Weng Z, Angelidou A, Kempuraj D, Alysandratos KD, Theoharides TC: Luteolin and thiosalicylate inhibit HgCl(2) and thimerosal-induced VEGF release from human mast cells. Int J Immunopathol Pharmacol. 2010, 23: 1015-1020.PubMed
99.
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: 7534-7539.PubMedCentralPubMed
100.
Sharma V, Mishra M, Ghosh S, Tewari R, Basu A, Seth P, Sen E: Modulation of interleukin-1beta mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection. Brain Res Bull. 2007, 73: 55-63.PubMed
101.
Jager AK, Saaby L: Flavonoids and the CNS. Molecules. 2011, 16: 1471-1485.PubMed
102.
Jones QR, Warford J, Rupasinghe HP, Robertson GS: Target-based selection of flavonoids for neurodegenerative disorders. Trends Pharmacol Sci. 2012, 33: 602-610.PubMed
103.
Theoharides TC, Zhang B, Conti P: Decreased mitochondrial function and increased brain inflammation in bipolar disorder and other neuropsychiatric diseases. J Clin Psychopharmacol. 2011, 31: 685-687.PubMed
104.
Aguirre A, Maturana CJ, Harcha PA, Saez JC: Possible involvement of TLRs and hemichannels in stress-induced CNS dysfunction via mastocytes, and glia activation. Mediators Inflamm. 2013, 2013: 893521.PubMedCentralPubMed
105.
Skaper SD, Giusti P, Facci L: Microglia and mast cells: two tracks on the road to neuroinflammation. FASEB J. 2012, 26: 3103-3117.PubMed
106.
Galli SJ, Borregaard N, Wynn TA: Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol. 2011, 12: 1035-1044.PubMedCentralPubMed
107.
108.
Theoharides TC: Mast cell: a neuroimmunoendocrine master player. Int J Tissue React. 1996, 18: 1-21.PubMed
109.
Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, Donald-Smith GP, Gao H, Hennessy L, Finnerty CC, Lopez CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, et al: Genomic responses in mouse models poorly mimic human inflammatory diseases. PNAS. 2013, 110: 3507-3512.PubMedCentralPubMed
Metadata
Title
Isoflavones inhibit poly(I:C)-induced serum, brain, and skin inflammatory mediators - relevance to chronic fatigue syndrome
Authors
Magdalini Vasiadi
Jennifer Newman
Theoharis C Theoharides
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2014
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-014-0168-5

Other articles of this Issue 1/2014

Journal of Neuroinflammation 1/2014 Go to the issue

Research

Tauroursodeoxycholic acid reduces glial cell activation in an animal model of acute neuroinflammation

Research

Toll-like 4 receptor inhibitor TAK-242 decreases neuroinflammation in rat brain frontal cortex after stress

Research

Exacerbation of blast-induced ocular trauma by an immune response

Research

Macrophages migrate in an activation-dependent manner to chemokines involved in neuroinflammation

Research

The immune response after hypoxia-ischemia in a mouse model of preterm brain injury

Research

Platelet-activating factors are associated with cognitive deficits in depressed coronary artery disease patients: a hypothesis-generating study