{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:38:21Z","timestamp":1791409101898,"version":"4.3.3"},"reference-count":90,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Propolis, a product of the honey bee, has been used in traditional medicine for many years. A hydrophobic bioactive polyphenolic ester, caffeic acid phenethyl ester (CAPE), is one of the most extensively investigated active components of propolis. Several studies have indicated that CAPE has a broad spectrum of pharmacological activities as anti-oxidant, anti-inflammatory, anti-viral, anti-fungal, anti-proliferative, and anti-neoplastic properties. This review largely describes CAPE neuroprotective effects in many different conditions and summarizes its molecular mechanisms of action. CAPE was found to have a neuroprotective effect on different neurodegenerative disorders. At the basis of these effects, CAPE has the ability to protect neurons from several underlying causes of various human neurologic diseases, such as oxidative stress, apoptosis dysregulation, and brain inflammation. CAPE can also protect the nervous system from some diseases which negatively affect it, such as diabetes, septic shock, and hepatic encephalopathy, while numerous studies have demonstrated the neuroprotective effects of CAPE against adverse reactions induced by different neurotoxic substances. The potential role of CAPE in protecting the central nervous system (CNS) from secondary injury following various CNS ischemic conditions and CAPE anti-cancer activity in CNS is also reviewed. The structure\u2013activity relationship of CAPE synthetic derivatives is discussed as well.<\/jats:p>","DOI":"10.3390\/biom11020176","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T05:23:05Z","timestamp":1611811385000},"page":"176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["CAPE and Neuroprotection: A Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8042-6009","authenticated-orcid":false,"given":"Marwa","family":"Balaha","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d, Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, 33516 Kafr El Sheikh, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"De Filippis","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d, Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Cataldi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d, Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-993X","authenticated-orcid":false,"given":"Viviana","family":"di Giacomo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d, Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Menezes da Silveira, C.C., Luz, D.A., da Silva, C.C., Prediger, R.D., Martins, M.D., Martins, M.A., Fontes-J\u00fanior, E.A., and Maia, C.S. (2020). Propolis: A useful agent on psychiatric and neurological disorders? A focus on CAPE and pinocembrin components. Med. Res. Rev.","DOI":"10.1002\/med.21757"},{"key":"ref_2","unstructured":"Watson, R.R., Preedy, V.R., and Zibadi, S. (2018). Chapter 31\u2014CAPE and Tympanosclerosis. Polyphenols: Mechanisms of Action in Human Health and Disease, Elsevier. [2nd ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.jep.2010.10.032","article-title":"Propolis: Is there a potential for the development of new drugs?","volume":"133","author":"Sforcin","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/697390","article-title":"Recent progress of propolis for its biological and chemical compositions and its botanical origin","volume":"2013","author":"Toreti","year":"2013","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/BF01941717","article-title":"Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis","volume":"44","author":"Grunberger","year":"1988","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.5455\/spatula.20110208013739","article-title":"The medical usage of caffeic acid phenethyl ester (CAPE), an active compound of propolis, in neurological disorders and emergencies","volume":"1","author":"Akyol","year":"2011","journal-title":"Spatula DD"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"821","DOI":"10.3109\/09637486.2011.585963","article-title":"Caffeic acid phenethyl ester (CAPE): Correlation of structure and antioxidant properties","volume":"62","year":"2011","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1021\/jf063477o","article-title":"In Vitro and in vivo stability of caffeic acid phenethyl ester, a bioactive compound of propolis","volume":"55","author":"Celli","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/iub.1189","article-title":"Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: A review on its anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects","volume":"65","author":"Tolba","year":"2013","journal-title":"IUBMB Life"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Murtaza, G., Karim, S., Akram, M.R., Khan, S.A., Azhar, S., Mumtaz, A., and Bin Asad, M.H.H. (2014). Caffeic acid phenethyl ester and therapeutic potentials. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/145342"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"108334","DOI":"10.1016\/j.neuropharm.2020.108334","article-title":"Caffeic acid phenethyl ester counteracts doxorubicin-induced chemobrain in Sprague-Dawley rats: Emphasis on the modulation of oxidative stress and neuroinflammation","volume":"181","author":"Ali","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"221","DOI":"10.5603\/FM.a2018.0085","article-title":"Evaluation of PECAM-1 and p38 MAPK expressions in cerebellum tissue of rats treated with caffeic acid phenethyl ester: A biochemical and immunohistochemical study","volume":"78","author":"Deveci","year":"2019","journal-title":"Folia Morphol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1472-8206.2009.00782.x","article-title":"The ultrastructural and biochemical evidences of the beneficial effects of chronic caffeic acid phenethyl ester and melatonin administration on brain and cerebellum of aged rats","volume":"24","year":"2010","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S0736-5748(03)00090-X","article-title":"Caffeic acid phenethyl ester blocks apoptosis induced by low potassium in cerebellar granule cells","volume":"21","author":"Amodio","year":"2003","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1007\/s11064-004-7038-y","article-title":"Caffeic acid phenethyl ester exerts a neuroprotective effect on CNS against pentylenetetrazol-induced seizures in mice","volume":"29","author":"Ilhan","year":"2004","journal-title":"Neurochem. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26885","DOI":"10.1074\/jbc.M400356200","article-title":"Stimulatory actions of caffeic acid phenethyl ester, a known inhibitor of NF-\u03baB activation, on Ca2+-activated K+ current in pituitary GH3 cells","volume":"279","author":"Lin","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.yebeh.2013.08.002","article-title":"Caffeic acid phenethyl ester prevents apoptotic cell death in the developing rat brain after pentylenetetrazole-induced status epilepticus","volume":"29","author":"Bayram","year":"2013","journal-title":"Epilepsy Behav."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.neuroscience.2008.06.056","article-title":"Caffeic acid phenethyl ester prevents cerebellar granule neurons (CGNs) against glutamate-induced neurotoxicity","volume":"155","author":"Wei","year":"2008","journal-title":"Neuroscience"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.neuro.2014.09.007","article-title":"Caffeic acid phenethyl ester (CAPE) protects PC12 cells from MPP+ toxicity by inducing the expression of neuron-typical proteins","volume":"45","author":"Martins","year":"2014","journal-title":"Neurotoxicology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0169-328X(03)00178-5","article-title":"Caffeic acid phenethyl ester (CAPE) prevents inflammatory stress in organotypic hippocampal slice cultures","volume":"115","author":"Montpied","year":"2003","journal-title":"Mol. Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1471-4159.2007.05193.x","article-title":"Differential regulation of c-Jun N-terminal kinase and NF-\u03baB pathway by caffeic acid phenethyl ester in astroglial and monocytic cells","volume":"105","author":"Choi","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_22","first-page":"747","article-title":"Caffeic acid phenethyl ester induces adrenoleukodystrophy (Abcd2) gene in human X-ALD fibroblasts and inhibits the proinflammatory response in Abcd1\/2 silenced mouse primary astrocytes","volume":"1831","author":"Singh","year":"2013","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.freeradbiomed.2004.04.022","article-title":"Protective effects of caffeic acid phenethyl ester against experimental allergic encephalomyelitis-induced oxidative stress in rats","volume":"37","author":"Ilhan","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.freeradbiomed.2009.01.019","article-title":"An in vitro screening cascade to identify neuroprotective antioxidants in ALS","volume":"46","author":"Barber","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.neuroscience.2011.12.025","article-title":"Caffeic acid phenethyl ester extends survival of a mouse model of amyotrophic lateral sclerosis","volume":"205","author":"Fontanilla","year":"2012","journal-title":"Neuroscience"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5572","DOI":"10.3390\/ijms16035572","article-title":"Regulatory effects of caffeic acid phenethyl ester on neuroinflammation in microglial cells","volume":"16","author":"Tsai","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.neulet.2005.04.023","article-title":"The flavanoide caffeic acid phenethyl ester blocks 6-hydroxydopamine-induced neurotoxicity","volume":"383","author":"Noelker","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.lfs.2006.03.050","article-title":"Caffeic acid phenethyl ester blocks free radical generation and 6-hydroxydopamine-induced neurotoxicity","volume":"79","author":"Ma","year":"2006","journal-title":"Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.neuroscience.2012.12.041","article-title":"Caffeic acid phenethyl ester protects against the dopaminergic neuronal loss induced by 6-hydroxydopamine in rats","volume":"233","author":"Silva","year":"2013","journal-title":"Neuroscience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1111\/j.1476-5381.2012.01833.x","article-title":"Caffeic acid phenethyl ester protects nigral dopaminergic neurons via dual mechanisms involving haem oxygenase-1 and brain-derived neurotrophic factor","volume":"166","author":"Kurauchi","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.pharep.2018.08.004","article-title":"Caffeic acid improves locomotor activity and lessens inflammatory burden in a mouse model of rotenone-induced nigral neurodegeneration: Relevance to Parkinson\u2019s disease therapy","volume":"71","author":"Zaitone","year":"2019","journal-title":"Pharmacol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.pestbp.2017.11.002","article-title":"Chlorpyrifos-induced parkinsonian model in mice: Behavior, histopathology and biochemistry","volume":"144","author":"Deveci","year":"2018","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.neuroscience.2011.04.009","article-title":"Caffeic acid phenethyl ester prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration","volume":"188","author":"Fontanilla","year":"2011","journal-title":"Neuroscience"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.biopha.2018.02.089","article-title":"Caffeic acid phenethyl ester rescued streptozotocin-induced memory loss through PI3-kinase dependent pathway","volume":"101","author":"Kumar","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.4103\/0973-1296.203974","article-title":"Caffeic acid phenethyl ester (CAPE) prevents development of STZ-ICV induced dementia in rats","volume":"13","author":"Kumar","year":"2017","journal-title":"Pharmacogn. Mag."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"605","DOI":"10.14336\/AD.2017.0903","article-title":"Neuroprotective effect of caffeic acid phenethyl ester in a mouse model of Alzheimer\u2019s disease involves Nrf2\/HO-1 pathway","volume":"9","author":"Morroni","year":"2018","journal-title":"Aging Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.pnpbp.2007.01.029","article-title":"Oxidative stress in prefrontal cortex of rat exposed to MK-801 and protective effects of CAPE","volume":"31","author":"Ozyurt","year":"2007","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11010-008-9719-3","article-title":"Caffeic acid phenethyl ester (CAPE) protects brain against oxidative stress and inflammation induced by diabetes in rats","volume":"312","author":"Celik","year":"2008","journal-title":"Mol. Cell. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/S1413-8670(11)70201-X","article-title":"Propolis derivatives inhibit the systemic inflammatory response and protect hepatic and neuronal cells in acute septic shock","volume":"15","author":"Korish","year":"2011","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.pnpbp.2010.07.034","article-title":"Effects of caffeic acid phenethyl ester on thioacetamide-induced hepatic encephalopathy in rats","volume":"34","author":"Fadillioglu","year":"2010","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_41","first-page":"4863","article-title":"Caffeic acid phenethyl ester attenuates nuclear factor-\u03baB-mediated inflammatory responses in M\u00fcller cells and protects against retinal ganglion cell death","volume":"19","author":"Jia","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.tox.2005.10.014","article-title":"The activity of adenosine deaminase and the level of nitric oxide in spinal cord of methotrexate administered rats: Protective effect of caffeic acid phenethyl ester","volume":"218","author":"Uzar","year":"2006","journal-title":"Toxicology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s11010-006-9196-5","article-title":"The activities of antioxidant enzymes and the level of malondialdehyde in cerebellum of rats subjected to methotrexate: Protective effect of caffeic acid phenethyl ester","volume":"291","author":"Uzar","year":"2006","journal-title":"Mol. Cell. Biochem."},{"key":"ref_44","first-page":"12","article-title":"Ameliorating Role of Caffeic Acid Phenethyl Ester (CAPE) Against Methotrexate-Induced Oxidative Stress in the Sciatic Nerve, Spinal Cord and Brain Stem Tissues of Rats","volume":"16","author":"Uzar","year":"2010","journal-title":"Turk. J. Neurol.\/Turk Noroloji Derg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1177\/0748233713500817","article-title":"Protective effects of caffeic acid phenethyl ester on ifosfamide-induced central neurotoxicity in rats","volume":"32","author":"Ginis","year":"2016","journal-title":"Toxicol. Ind. Health"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s12640-017-9849-z","article-title":"Caffeic Acid Phenethyl Ester (CAPE) Protects PC12 Cells from Cisplatin-Induced Neurotoxicity by Activating the NGF-Signaling Pathway","volume":"34","author":"Ferreira","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s12640-019-00042-w","article-title":"Caffeic acid phenethyl ester (CAPE) protects PC12 cells against cisplatin-induced neurotoxicity by activating the AMPK\/SIRT1, MAPK\/Erk, and PI3k\/Akt signaling pathways","volume":"36","author":"Ferreira","year":"2019","journal-title":"Neurotox. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/nrc.10089","article-title":"Effects of caffeic acid phenethyl ester against doxorubicin-induced neuronal oxidant injury","volume":"33","author":"Fadillioglu","year":"2003","journal-title":"Neurosci. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1080\/00313020701444481","article-title":"The neuroprotective effects of caffeic acid phenethyl ester (CAPE) in the hippocampal formation of cigarette smoke exposed rabbits","volume":"39","author":"Eser","year":"2007","journal-title":"Pathology"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ba\u015farslan, S.K., \u00d6s\u00fcn, A., \u015eenol, S., Korkmaz, M., \u00d6zkan, \u00dc., and Kaplan, I. (2015). Protective effects of intralipid and caffeic acid phenyl esther (CAPE) on neurotoxicity induced by ethanol in rats. Turk. Neurosurg., 27.","DOI":"10.5137\/1019-5149.JTN.14463-15.2"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.neulet.2012.12.051","article-title":"Protective effects of caffeic acid and caffeic acid phenethyl ester against acrolein-induced neurotoxicity in HT22 mouse hippocampal cells","volume":"535","author":"Huang","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.biopha.2017.04.073","article-title":"Caffeic acid phenethyl ester protects the brain against hexavalent chromium toxicity by enhancing endogenous antioxidants and modulating the JAK\/STAT signaling pathway","volume":"91","author":"Mahmoud","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"111636","DOI":"10.1016\/j.fct.2020.111636","article-title":"Caffeic acid phenethyl ester reversed cadmium-induced cell death in hippocampus and cortex and subsequent cognitive disorders in mice: Involvements of AMPK\/SIRT1 pathway and amyloid-tau-neuroinflammation axis","volume":"144","author":"Hao","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_54","first-page":"837","article-title":"Effects of intralipid and caffeic acid phenethyl ester on neurotoxicity, oxidative stress, and acetylcholinesterase activity in acute chlorpyriphos intoxication","volume":"7","author":"Ozkan","year":"2014","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_55","first-page":"2953","article-title":"Assesment the role of oxidative stress and efficacy of caffeic acid phenethyl ester (CAPE) on neurotoxicity induced by isoniazid and ethambutol in a rat model","volume":"18","author":"Uzar","year":"2014","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.3892\/mmr.2016.5586","article-title":"Neuroprotective effects of caffeic acid phenethyl ester against sevoflurane-induced neuronal degeneration in the hippocampus of neonatal rats involve MAPK and PI3K\/Akt signaling pathways","volume":"14","author":"Wang","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_57","first-page":"283","article-title":"Effects of caffeic acid phenethyl ester and alpha-tocopherol on reperfusion injury in rat brain","volume":"21","author":"Irmak","year":"2003","journal-title":"Cell Biochem. Funct. Cell. Biochem. Modul. Act. Agents Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1016\/j.lfs.2005.10.017","article-title":"Caffeic acid phenethyl ester ameliorates cerebral infarction in rats subjected to focal cerebral ischemia","volume":"78","author":"Tsai","year":"2006","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1471-4159.2007.04526.x","article-title":"Caffeic acid phenethyl ester reduces neurovascular inflammation and protects rat brain following transient focal cerebral ischemia","volume":"102","author":"Khan","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.brainres.2008.01.053","article-title":"Caffeic acid phenethyl ester protects rabbit brains against permanent focal ischemia by antioxidant action: A biochemical and planimetric study","volume":"1201","author":"Serarslan","year":"2008","journal-title":"Brain Res."},{"key":"ref_61","unstructured":"Serarslan, Y., Bal, R., Altu\u011f, M.E., Konta\u015f, T., and Melek, I.M. (2009). Caffeic acid phenethyl ester decreases the level of S-100B protein after middle cerebral AFTER occusion in rabbits. Pak. J. Pharm. Sci., 22."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"80","DOI":"10.5414\/NPP26080","article-title":"Effects of caffeic acid phenethyl ester on cerebral cortex: Structural changes resulting from middle cerebral artery ischemia reperfusion","volume":"26","author":"Cengiz","year":"2007","journal-title":"Clin. Neuropathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4196\/kjpp.2018.22.1.101","article-title":"Caffeic acid phenethyl ester protects against photothrombotic cortical ischemic injury in mice","volume":"22","author":"Hwang","year":"2018","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.bbagen.2008.01.002","article-title":"Caffeic acid phenethyl ester and its related compounds limit the functional alterations of the isolated mouse brain and liver mitochondria submitted to in vitro anoxia\u2013reoxygenation: Relationship to their antioxidant activities","volume":"1780","author":"Feng","year":"2008","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1093\/brain\/awh316","article-title":"Caffeic acid phenethyl ester prevents neonatal hypoxic\u2013ischaemic brain injury","volume":"127","author":"Wei","year":"2004","journal-title":"Brain"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ijdevneu.2005.12.002","article-title":"Caffeic acid phenethyl ester (CAPE) attenuates cerebral vasospasm after experimental subarachnoidal haemorrhage by increasing brain nitric oxide levels","volume":"24","author":"Aladag","year":"2006","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e736","DOI":"10.1016\/j.wneu.2020.03.058","article-title":"The Impact of Propolis Factor Caffeic Acid Phenethyl-Ester on the Cerebral Vasospasm and Early Brain Damage in the Exparimentally Induced Subarachnoid Hemorrhage on Rats","volume":"138","author":"Palaz","year":"2020","journal-title":"World Neurosurg."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/S1010-7940(99)00246-8","article-title":"The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia\/reperfusion injury in rabbits","volume":"16","author":"Ilhan","year":"1999","journal-title":"Eur. J. Cardio-Thoracic Surg."},{"key":"ref_69","first-page":"96","article-title":"The effects of caffeic acid phenethyl ester on inflammatory cytokines after acute spinal cord injury","volume":"21","author":"Ak","year":"2015","journal-title":"Ulus Travma Acil Cerrahi Derg"},{"key":"ref_70","first-page":"437","article-title":"Histopathological evaluation of the effects of CAPE in experimental spinal cord injury","volume":"26","author":"Aydin","year":"2016","journal-title":"Turk. Neurosurg."},{"key":"ref_71","first-page":"625","article-title":"Effects of intrathecal caffeic acid phenethyl ester (CAPE) on IL-6 and TNF-\u03b1 levels and local inflammatory responses in spinal cord injuries","volume":"28","author":"Akgun","year":"2018","journal-title":"Turk. Neurosurg."},{"key":"ref_72","first-page":"20","article-title":"Effects of intrathecal caffeic acid phenethyl ester and methylprednisolone on oxidant\/antioxidant status in traumatic spinal cord injuries","volume":"76","author":"Gocmez","year":"2015","journal-title":"J. Neurol. Surg. Part A Central Eur. Neurosurg."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2220\/biomedres.32.1","article-title":"Caffeic acid phenethyl ester reduces spinal cord injury-evoked locomotor dysfunction","volume":"32","author":"Kasai","year":"2011","journal-title":"Biomed. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.amsu.2020.04.015","article-title":"Decreased neutrophil levels in mice with traumatic brain injury after cape administration","volume":"54","author":"Nasution","year":"2020","journal-title":"Ann. Med. Surg."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1089\/neu.2011.1858","article-title":"Caffeic acid phenethyl ester protects blood\u2013brain barrier integrity and reduces contusion volume in rodent models of traumatic brain injury","volume":"29","author":"Zhao","year":"2012","journal-title":"J. Neurotrauma"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s10735-011-9376-9","article-title":"Neuroprotective effects of caffeic acid phenethyl ester on experimental traumatic brain injury in rats","volume":"43","author":"Kerman","year":"2012","journal-title":"J. Mol. Histol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1002\/jnr.24279","article-title":"Combined treatment with GSNO and CAPE accelerates functional recovery via additive antioxidant activities in a mouse model of TBI","volume":"96","author":"Khan","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref_78","unstructured":"(2020, November 03). National Cancer Institute (Cancer Stat Facts: Brain and Other Nervous System Cancer), Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/brain.html."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.canlet.2007.07.006","article-title":"N-Acetyl cysteine and caffeic acid phenethyl ester sensitize astrocytoma cells to Fas-mediated cell death in a redox-dependent manner","volume":"257","author":"Choi","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2013.09.105","article-title":"Caffeic acid phenethyl ester downregulates phospholipase D1 via direct binding and inhibition of NF\u03baB transactivation","volume":"442","author":"Park","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Morin, P., St-Coeur, P.-D., Doiron, J.A., Cormier, M., Poitras, J.J., Surette, M.E., and Touaibia, M. (2017). Substituted caffeic and ferulic acid phenethyl esters: Synthesis, leukotrienes biosynthesis inhibition, and cytotoxic activity. Molecules, 22.","DOI":"10.3390\/molecules22071124"},{"key":"ref_82","first-page":"226","article-title":"CAPE (caffeic acid phenethyl ester)-based propolis extract (Bio 30) suppresses the growth of human neurofibromatosis (NF) tumor xenografts in mice","volume":"23","author":"Demestre","year":"2009","journal-title":"Phytother. Res. Int. J. Devoted Pharmacol. Toxicol. Eval. Nat. Product Deriv."},{"key":"ref_83","first-page":"615","article-title":"Studies on the structure-activity relationship of caffeate derivatives as neuroprotective agents","volume":"28","author":"Wu","year":"2019","journal-title":"J. Chin. Pharm. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5046","DOI":"10.1021\/jf500464k","article-title":"Synthesis of caffeic acid phenethyl ester derivatives, and their cytoprotective and neuritogenic activities in PC12 cells","volume":"62","author":"Shi","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.bbr.2017.04.012","article-title":"Neuroprotective effect of three caffeic acid derivatives via ameliorate oxidative stress and enhance PKA\/CREB signaling pathway","volume":"328","author":"Fu","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_86","first-page":"1","article-title":"FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Protects against Oxidative Stress-Mediated Neuronal Cell Apoptosis and Scopolamine-Induced Cognitive Impairment by Activating Nrf2\/HO-1 Signaling","volume":"2019","author":"Wan","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5589","DOI":"10.1016\/j.bmc.2013.05.043","article-title":"Design, synthesis and pharmacological evaluation of (E)-3, 4-dihydroxy styryl sulfonamides derivatives as multifunctional neuroprotective agents against oxidative and inflammatory injury","volume":"21","author":"Ning","year":"2013","journal-title":"Bioorganic Med. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s12035-013-8474-y","article-title":"Anti-neuroinflammatory effect of a novel caffeamide derivative, KS370G, in microglial cells","volume":"48","author":"Lu","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7584","DOI":"10.1021\/acs.jmedchem.6b00666","article-title":"Development of blood\u2013brain barrier permeable nitrocatechol-based catechol O-methyltransferase inhibitors with reduced potential for hepatotoxicity","volume":"59","author":"Silva","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ejmech.2019.02.006","article-title":"Repurposing nitrocatechols: 5-Nitro-\u03b1-cyanocarboxamide derivatives of caffeic acid and caffeic acid phenethyl ester effectively inhibit aggregation of tau-derived hexapeptide AcPHF6","volume":"167","author":"Silva","year":"2019","journal-title":"Eur. J. Med. Chem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/2\/176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:16:29Z","timestamp":1760159789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/2\/176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,28]]},"references-count":90,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["biom11020176"],"URL":"https:\/\/doi.org\/10.3390\/biom11020176","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,28]]}}}