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http://dx.doi.org/10.4196/kjpp.2018.22.1.101

Caffeic acid phenethyl ester protects against photothrombotic cortical ischemic injury in mice  

Hwang, Sun Ae (Department of Pharmacology, Pusan National University School of Medicine)
Kim, Chi Dae (Department of Pharmacology, Pusan National University School of Medicine)
Lee, Won Suk (Department of Pharmacology, Pusan National University School of Medicine)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.22, no.1, 2018 , pp. 101-110 More about this Journal
Abstract
In this study, we aimed to investigate the neuroprotective effects of caffeic acid phenethyl ester (CAPE), an active component of propolis purified from honeybee hives, on photothrombotic cortical ischemic injury in mice. Permanent focal ischemia was achieved in the medial frontal and somatosensory cortices of anesthetized male C57BL/6 mice by irradiation of the skull with cold light laser in combination with systemic administration of rose bengal. The animals were treated with CAPE (0.5-5 mg/kg, i.p.) twice 1 and 6 h after ischemic insult. CAPE significantly reduced the infarct size as well as the expression of tumor necrosis $factor-{\alpha}$, hypoxiainducible $factor-1{\alpha}$ monocyte chemoattractant protein-1, $interleukin-1{\alpha}$, and indoleamine 2,3-dioxygenase in the cerebral cortex ipsilateral to the photothrombosis. Moreover, it induced an increase in heme oxygenase-1 immunoreactivity and interleukin-10 expression. These results suggest that CAPE exerts a remarkable neuroprotective effect on ischemic brain injury via its anti-inflammatory properties, thereby providing a benefit to the therapy of cerebral infarction.
Keywords
Caffeic acid phenethyl ester; Cerebral ischemia; Chemokine; Cytokine; Neuroinflammation;
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1 Jones NM, Bergeron M. Hypoxic preconditioning induces changes in HIF-1 target genes in neonatal rat brain. J Cereb Blood Flow Metab. 2001;21:1105-1114.   DOI
2 Mu D, Jiang X, Sheldon RA, Fox CK, Hamrick SE, Vexler ZS, Ferriero DM. Regulation of hypoxia-inducible factor 1alpha and induction of vascular endothelial growth factor in a rat neonatal stroke model. Neurobiol Dis. 2003;14:524-534.   DOI
3 Sharp FR, Bergeron M, Bernaudin M. Hypoxia-inducible factor in brain. Adv Exp Med Biol. 2001;502:273-291.
4 Halterman MW, Miller CC, Federoff HJ. Hypoxia-inducible factor-$1{\alpha}$ mediates hypoxia-induced delayed neuronal death that involves p53. J Neurosci. 1999;19:6818-6824.   DOI
5 Chen C, Hu Q, Yan J, Yang X, Shi X, Lei J, Chen L, Huang H, Han J, Zhang JH, Zhou C. Early inhibition of HIF-$1{\alpha}$ with small interfering RNA reduces ischemic-reperfused brain injury in rats. Neurobiol Dis. 2009;33:509-517.   DOI
6 Lee PJ, Jiang BH, Chin BY, Iyer NV, Alam J, Semenza GL, Choi AM. Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J Biol Chem. 1997;272:5375-5381.   DOI
7 Dawn B, Bolli R. HO-1 induction by HIF-1: a new mechanism for delayed cardioprotection? Am J Physiol Heart Circ Physiol . 2005; 289:H522-524.   DOI
8 Panahian N, Yoshiura M, Maines MD. Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. J Neurochem. 1999;72:1187-1203.
9 Demougeot C, Van Hoecke M, Bertrand N, Prigent-Tessier A, Mossiat C, Beley A, Marie C. Cytoprotective efficacy and mechanisms of the liposoluble iron chelator 2,2'-dipyridyl in the rat photothrombotic ischemic stroke model. J Pharmacol Exp Ther. 2004;311:1080-1087.   DOI
10 Fu R, Zhao ZQ, Zhao HY, Zhao JS, Zhu XL. Expression of heme oxygenase-1 protein and messenger RNA in permanent cerebral ischemia in rats. Neurol Res. 2006;28:38-45.   DOI
11 Che X, Ye W, Panga L, Wu DC, Yang GY. Monocyte chemoattractant protein-1 expressed in neurons and astrocytes during focal ischemia in mice. Brain Res. 2001;902:171-177.   DOI
12 Hughes PM, Allegrini PR, Rudin M, Perry VH, Mir AK, Wiessner C. Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model. J Cereb Blood Flow Metab. 2002;22:308-317.   DOI
13 Chen Y, Hallenbeck JM, Ruetzler C, Bol D, Thomas K, Berman NE, Vogel SN. Overexpression of monocyte chemoattractant protein 1 in the brain exacerbates ischemic brain injury and is associated with recruitment of inflammatory cells. J Cereb Blood Flow Metab. 2003;23:748-755.   DOI
14 Konsman JP, Blond D, Vigues S. Neurobiology of interleukin-1 receptors: getting the message. Eur Cytokine Netw. 2000;11:699-702.
15 Harkness KA, Sussman JD, Davies-Jones GA, Greenwood J, Woodroofe MN. Cytokine regulation of MCP-1 expression in brain and retinal microvascular endothelial cells. J Neuroimmunol. 2003;142: 1-9.   DOI
16 Perez-De La Cruz V, Konigsberg M, Santamaria A. Kynurenine pathway and disease: an overview. CNS Neurol Disord Drug Targets. 2007;6:398-410.   DOI
17 Rothwell NJ, Luheshi GN. Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci. 2000;23:618-625.   DOI
18 Saito K, Nowak TS Jr, Suyama K, Quearry BJ, Saito M, Crowley JS, Markey SP, Heyes MP. Kynurenine pathway enzymes in brain: responses to ischemic brain injury versus systemic immune activation. J Neurochem. 1993;61:2061-2070.   DOI
19 Spalletta G, Bossu P, Ciaramella A, Bria P, Caltagirone C, Robinson RG. The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines. Mol Psychiatry. 2006;11:984-991.   DOI
20 Touzani O, Boutin H, Chuquet J, Rothwell N. Potential mechanisms of interleukin-1 involvement in cerebral ischaemia. J Neuroimmunol. 1999;100:203-215.   DOI
21 Luheshi NM, Kovacs KJ, Lopez-Castejon G, Brough D, Denes A. Interleukin-$1{\alpha}$ expression precedes IL-$1{\beta}$ after ischemic brain injury and is localised to areas of focal neuronal loss and penumbral tissues. J Neuroinflammation. 2011;8:186.   DOI
22 Frijns CJ, Kappelle LJ. Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke. 2002;33:2115-2122.   DOI
23 Ooboshi H, Ibayashi S, Shichita T, Kumai Y, Takada J, Ago T, Arakawa S, Sugimori H, Kamouchi M, Kitazono T, Iida M. Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia. Circulation. 2005;111:913-919.   DOI
24 Saito K, Nowak TS Jr, Markey SP, Heyes MP. Mechanism of delayed increases in kynurenine pathway metabolism in damaged brain regions following transient cerebral ischemia. J Neurochem. 1993;60:180-192.   DOI
25 Denes A, Thornton P, Rothwell NJ, Allan SM. Inflammation and brain injury: acute cerebral ischaemia, peripheral and central inflammation. Brain Behav Immun. 2010;24:708-723.   DOI
26 Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 2017;135:e146-603.   DOI
27 National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581-1587.   DOI
28 Lambrinos A, Schaink AK, Dhalla I, Krings T, Casaubon LK, Sikich N, Lum C, Bharatha A, Pereira VM, Stotts G, Saposnik G, Kelloway L, Xie X, Hill MD. Mechanical thrombectomy in acute ischemic stroke: a systematic review. Can J Neurol Sci. 2016;43:455-460.   DOI
29 Lakhan SE, Kirchgessner A, Hofer M. Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med. 2009;7:97.   DOI
30 Amantea D, Nappi G, Bernardi G, Bagetta G, Corasaniti MT. Postischemic brain damage: pathophysiology and role of inflammatory mediators. FEBS J. 2009;276:13-26.   DOI
31 Schilling M, Besselmann M, Leonhard C, Mueller M, Ringelstein EB, Kiefer R. Microglial activation precedes and predominates over macrophage infiltration in transient focal cerebral ischemia: a study in green fluorescent protein transgenic bone marrow chimeric mice. Exp Neurol . 2003;183:25-33.   DOI
32 Agata I1. Studies on caffeic acid derivatives in medicinal plants. Yakugaku Zasshi . 1999;119:237-248.   DOI
33 Tanaka R, Komine-Kobayashi M, Mochizuki H, Yamada M, Furuya T, Migita M, Shimada T, Mizuno Y, Urabe T. Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia. Neuroscience. 2003;117:531-539.   DOI
34 Gerhard A, Neumaier B, Elitok E, Glatting G, Ries V, Tomczak R, Ludolph AC, Reske SN. In vivo imaging of activated microglia using [11C]PK11195 and positron emission tomography in patients after ischemic stroke. Neuroreport. 2000;11:2957-2960.   DOI
35 Price CJ, Menon DK, Peters AM, Ballinger JR, Barber RW, Balan KK, Lynch A, Xuereb JH, Fryer T, Guadagno JV, Warburton EA. Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study. Stroke. 2004;35:1659-1664.   DOI
36 Sud'ina GF, Mirzoeva OK, Pushkareva MA, Korshunova GA, Sumbatyan NV, Varfolomeev SD. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett. 1993;329:21-24.   DOI
37 Park JH, Lee JK, Kim HS, Chung ST, Eom JH, Kim KA, Chung SJ, Paik SY, Oh HY. Immunomodulatory effect of caffeic acid phenethyl ester in Balb/c mice. Int Immunopharmacol. 2004;4:429-436.   DOI
38 Altug ME, Serarslan Y, Bal R, Kontas T, Ekici F, Melek IM, Aslan H, Duman T. Caffeic acid phenethyl ester protects rabbit brains against permanent focal ischemia by antioxidant action: a biochemical and planimetric study. Brain Res. 2008;1201:135-142.   DOI
39 Ilhan A, Akyol O, Gurel A, Armutcu F, Iraz M, Oztas E. Protective effects of caffeic acid phenethyl ester against experimental allergic encephalomyelitis-induced oxidative stress in rats. Free Radic Biol Med. 2004;37:386-394.   DOI
40 Khan M, Elango C, Ansari MA, Singh I, Singh AK. Caffeic acid phenethyl ester reduces neurovascular inflammation and protects rat brain following transient focal cerebral ischemia. J Neurochem. 2007;102:365-377.   DOI
41 Sforcin JM. Propolis and the immune system: a review. J Ethnopharmacol. 2007;113:1-14.   DOI
42 Shin TK, Kang MS, Lee HY, Seo MS, Kim SG, Kim CD, Lee WS. Fluoxetine and sertraline attenuate postischemic brain injury in mice. Korean J Physiol Pharmacol. 2009;13:257-263.   DOI
43 Bederson JB, Pitts LH, Germano SM, Nishimura MC, Davis RL, Bartkowski HM. Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke. 1986;17:1304-1308.   DOI
44 Park CH, Shin TK, Lee HY, Kim SJ, Lee WS. Matrix metalloproteinase inhibitors attenuate neuroinflammation following focal cerebral ischemia in mice. Korean J Physiol Pharmacol. 2011;15:115-122.   DOI
45 Lee SK, Song L, Mata-Greenwood E, Kelloff GJ, Steele VE, Pezzuto JM. Modulation of in vitro biomarkers of the carcinogenic process by chemopreventive agents. Anticancer Res. 1999;19:35-44.
46 Castaldo S, Capasso F. Propolis, an old remedy used in modern medicine. Fitoterapia. 2002;73 Suppl 1:S1-6.   DOI
47 Ilhan A, Koltuksuz U, Ozen S, Uz E, Ciralik H, Akyol O. The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits. Eur J Cardiothorac Surg. 1999;16:458-463.   DOI
48 Fesen MR, Pommier Y, Leteurtre F, Hiroguchi S, Yung J, Kohn KW. Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds. Biochem Pharmacol. 1994;48: 595-608.   DOI
49 Uz E, Sogut S, Sahin S, Var A, Ozyurt H, Gulec M, Akyol O. The protective role of caffeic acid phenethyl ester (CAPE) on testicular tissue after testicular torsion and detorsion. World J Urol. 2002;20: 264-270.
50 Mohamadin AM, Hammad LN, El-Bab MF, Abdel Gawad HS. Attenuation of oxidative stress in plasma and tissues of rats with experimentally induced hyperthyroidism by caffeic acid phenylethyl ester. Basic Clin Pharmacol Toxicol. 2007;100:84-90.
51 Grome JJ, Gojowczyk G, Hofmann W, Graham DI. Quantitation of photochemically induced focal cerebral ischemia in the rat. J Cereb Blood Flow Metab. 1988;8:89-95.   DOI
52 Hossmann KA. Pathophysiology and therapy of experimental stroke. Cell Mol Neurobiol. 2006;26:1057-1083.
53 Astrup J, Siesjo BK, Symon L. Thresholds in cerebral ischemia - the ischemic penumbra. Stroke. 1981;12:723-725.   DOI
54 Liu T, Clark RK, McDonnell PC, Young PR, White RF, Barone FC, Feuerstein GZ. Tumor necrosis factor-a expression in ischemic neurons. Stroke. 1994;25:1481-1488.   DOI
55 GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385:117-171.   DOI
56 Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999;22:391-397.   DOI
57 Taylor RA, Sansing LH. Microglial responses after ischemic stroke and intracerebral hemorrhage. Clin Dev Immunol. 2013;2013:746068.
58 Jin R, Liu L, Zhang S, Nanda A, Li G. Role of inflammation and its mediators in acute ischemic stroke. J Cardiovasc Transl Res. 2013;6:834-851.   DOI
59 Mojsilovic-Petrovic J, Callaghan D, Cui H, Dean C, Stanimirovic DB, Zhang W. Hypoxia-inducible factor-1 (HIF-1) is involved in the regulation of hypoxia-stimulated expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and MCP-5 (Ccl12) in astrocytes. J Neuroinflammation. 2007;4:12.   DOI
60 Zaremba J, Losy J. Early TNF-${\alpha}$ levels correlate with ischaemic stroke severity. Acta Neurol Scand. 2001;104:288-295.   DOI
61 Sriram K, O'Callaghan JP. Divergent roles for tumor necrosis factoralpha in the brain. J Neuroimmune Pharmacol. 2007;2:140-153.   DOI
62 Chen C, Hu Q, Yan J, Lei J, Qin L, Shi X, Luan L, Yang L, Wang K, Han J, Nanda A, Zhou C. Multiple effects of 2ME2 and D609 on the cortical expression of HIF-1alpha and apoptotic genes in a middle cerebral artery occlusion-induced focal ischemia rat model. J Neurochem. 2007;102:1831-1841.   DOI
63 Helton R, Cui J, Scheel JR, Ellison JA, Ames C, Gibson C, Blouw B, Ouyang L, Dragatsis I, Zeitlin S, Johnson RS, Lipton SA, Barlow C. Brain-specific knock-out of hypoxia-inducible factor-1a reduces rather than increases hypoxic-ischemic damage. J Neurosci. 2005;25:4099-4107.   DOI