{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:07:13Z","timestamp":1790651233784,"version":"4.1.0"},"reference-count":82,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,7,22]],"date-time":"2018-07-22T00:00:00Z","timestamp":1532217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>In the prevention of neurodegeneration associated with aging and neurodegenerative diseases (Alzheimer\u2019s disease, Parkinson\u2019s disease), neuronal differentiation is of interest. In this context, neurotrophic factors are a family of peptides capable of promoting the growth, survival, and\/or differentiation of both developing and immature neurons. In contrast to these peptidyl compounds, polyphenols are not degraded in the intestinal tract and are able to cross the blood\u2013brain barrier. Consequently, they could potentially be used as therapeutic agents in neurodegenerative pathologies associated with neuronal loss, thus requiring the stimulation of neurogenesis. We therefore studied the ability to induce neuronal differentiation of two major polyphenols present in the Mediterranean diet: resveratrol (RSV), a major compound found in grapes and red wine, and apigenin (API), present in parsley, rosemary, olive oil, and honey. The effects of these compounds (RSV and API: 6.25\u201350 \u00b5M) were studied on murine neuro-2a (N2a) cells after 48 h of treatment without or with 10% fetal bovine serum (FBS). Retinoic acid (RA: 6.25\u201350 \u00b5M) was used as positive control. Neuronal differentiation was morphologically evaluated through the presence of dendrites and axons. Cell growth was determined by cell counting and cell viability by staining with fluorescein diacetate (FDA). Neuronal differentiation was more efficient in the absence of serum than with 10% FBS or 10% delipidized FBS. At concentrations inducing neuronal differentiation, no or slight cytotoxicity was observed with RSV and API, whereas RA was cytotoxic. Without FBS, RSV and API, as well as RA, trigger the neuronal differentiation of N2a cells via signaling pathways simultaneously involving protein kinase A (PKA)\/phospholipase C (PLC)\/protein kinase C (PKC) and MEK\/ERK. With 10% FBS, RSV and RA induce neuronal differentiation via PLC\/PKC and PKA\/PLC\/PKC, respectively. With 10% FBS, PKA and PLC\/PKC as well as MEK\/ERK signaling pathways were not activated in API-induced neuronal differentiation. In addition, the differentiating effects of RSV and API were not inhibited by cyclo[DLeu5] OP, an antagonist of octadecaneuropeptide (ODN) which is a neurotrophic factor. Moreover, RSV and API do not stimulate the expression of the diazepam-binding inhibitor (DBI), the precursor of ODN. Thus, RSV and API are able to induce neuronal differentiation, ODN and its receptor are not involved in this process, and the activation of the (PLC\/PKC) signaling pathway is required, except with apigenin in the presence of 10% FBS. These data show that RSV and API are able to induce neuronal differentiation and therefore mimic neurotrophin activity. Thus, RSV and API could be of interest in regenerative medicine to favor neurogenesis.<\/jats:p>","DOI":"10.3390\/diseases6030067","type":"journal-article","created":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T02:58:56Z","timestamp":1532401136000},"page":"67","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Induction of Neuronal Differentiation of Murine N2a Cells by Two Polyphenols Present in the Mediterranean Diet Mimicking Neurotrophins Activities: Resveratrol and Apigenin"],"prefix":"10.3390","volume":"6","author":[{"given":"Amira","family":"Namsi","sequence":"first","affiliation":[{"name":"Team Bio-PeroxIL, \u2018Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism\u2019 (EA7270)\/University Bourgogne Franche-Comt\u00e9\/Inserm, 21000 Dijon, France"},{"name":"UR\/11ES09, Lab. \u2018Functional Neurophysiology and Pathology\u2019, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Nury","sequence":"additional","affiliation":[{"name":"Team Bio-PeroxIL, \u2018Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism\u2019 (EA7270)\/University Bourgogne Franche-Comt\u00e9\/Inserm, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5746-8075","authenticated-orcid":false,"given":"Haithem","family":"Hamdouni","sequence":"additional","affiliation":[{"name":"Team Bio-PeroxIL, \u2018Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism\u2019 (EA7270)\/University Bourgogne Franche-Comt\u00e9\/Inserm, 21000 Dijon, France"},{"name":"LR12SP11 \u2018Molecular Biology Applied to Cardiovascular Diseases, Hereditary Nephropathies and Pharmacogenomics\u2019, Dept Biochemistry, CHU Sahloul, Sousse 4000, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Yammine","sequence":"additional","affiliation":[{"name":"Team Bio-PeroxIL, \u2018Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism\u2019 (EA7270)\/University Bourgogne Franche-Comt\u00e9\/Inserm, 21000 Dijon, France"},{"name":"Bioactive Molecules Research Laboratory, Doctoral School of Sciences and Technologies, Faculty of Sciences, Lebanese University, Beirut 1103, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4063-9680","authenticated-orcid":false,"given":"Anne","family":"Vejux","sequence":"additional","affiliation":[{"name":"Team Bio-PeroxIL, \u2018Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism\u2019 (EA7270)\/University Bourgogne Franche-Comt\u00e9\/Inserm, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2998-5873","authenticated-orcid":false,"given":"Dominique","family":"Vervandier-Fasseur","sequence":"additional","affiliation":[{"name":"Institut of Molecular Chemistry (ICMUB UMR 6302), Univ. Bourgogne Franche-Comt\u00e9, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6794-2690","authenticated-orcid":false,"given":"Norbert","family":"Latruffe","sequence":"additional","affiliation":[{"name":"Team Bio-PeroxIL, \u2018Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism\u2019 (EA7270)\/University Bourgogne Franche-Comt\u00e9\/Inserm, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olfa","family":"Masmoudi-Kouki","sequence":"additional","affiliation":[{"name":"UR\/11ES09, Lab. \u2018Functional Neurophysiology and Pathology\u2019, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-0172","authenticated-orcid":false,"given":"G\u00e9rard","family":"Lizard","sequence":"additional","affiliation":[{"name":"Team Bio-PeroxIL, \u2018Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism\u2019 (EA7270)\/University Bourgogne Franche-Comt\u00e9\/Inserm, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1753-4887.1998.tb01670.x","article-title":"Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance","volume":"56","author":"Bravo","year":"1998","journal-title":"Nutr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1093\/ajcn\/79.5.727","article-title":"Polyphenols: Food sources and bioavailability","volume":"79","author":"Manach","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1089\/ars.2012.4581","article-title":"Dietary (poly)phenolics in human health: Structures, bioavailability, and evidence of protective effects against chronic diseases","volume":"18","author":"Spencer","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.fct.2018.01.022","article-title":"Dietary polyphenols: Structures, bioavailability and protective effects against atherosclerosis","volume":"113","author":"Santhakumar","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.arr.2014.09.006","article-title":"Involvement of oxysterols in age-related diseases and ageing processes","volume":"18","author":"Zarrouk","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.chemphyslip.2017.03.001","article-title":"Dietary phytochemicals in the protection against oxysterol-induced damage","volume":"207","author":"Cilla","year":"2017","journal-title":"Chem. Phys. Lipids"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"504253","DOI":"10.1155\/2015\/504253","article-title":"Role of Polyphenols and Other Phytochemicals on Molecular Signaling","volume":"2015","author":"Upadhyay","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.2174\/0929867323666160627104022","article-title":"Neurotrophins\u2019modulation by olive polyphenols","volume":"23","author":"Carito","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"497","DOI":"10.2174\/1568026013394741","article-title":"Oxytosis: A novel form of programmed cell death","volume":"1","author":"Tan","year":"2001","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1159\/000095209","article-title":"Plant foods and brain aging: A critical appraisal","volume":"59","author":"Schaffer","year":"2006","journal-title":"Forum Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.nut.2017.06.008","article-title":"Mediterranean diet and colorectal cancer: A systematic review","volume":"43\u201344","author":"Farinetti","year":"2017","journal-title":"Nutrition"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gorzynik-Debicka, M., Przychodzen, P., Cappello, F., Kuban-Jankowska, A., Marino Gammazza, A., Knap, N., Wozniak, M., and Gorska-Ponikowska, M. (2018). Potential Health Benefits of Olive Oil and Plant Polyphenols. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030686"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"893","DOI":"10.3346\/jkms.2011.26.7.893","article-title":"Antiproliferation and redifferentiation in thyroid cancer cell lines by polyphenol phytochemicals","volume":"26","author":"Kang","year":"2011","journal-title":"J. Korean Med. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.bcp.2012.08.023","article-title":"Resveratrol initiates differentiation of mouse skeletal muscle-derived C2C12 myoblasts","volume":"84","author":"Kaminski","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.2174\/1381612811319340002","article-title":"Bioactive polyphenols from grapes and wine emphasized with resveratrol","volume":"19","author":"Latruffe","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3892\/or.2015.4346","article-title":"Resveratrol sensitizes glioblastoma-initiating cells to temozolomide by inducing cell apoptosis and promoting differentiation","volume":"35","author":"Li","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9949","DOI":"10.3390\/molecules18089949","article-title":"Neuroprotective, anti-amyloidogenic and neurotrophic effects of apigenin in an Alzheimer\u2019s disease mouse model","volume":"18","author":"Zhao","year":"2013","journal-title":"Molecules"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1651325","DOI":"10.1155\/2017\/1651325","article-title":"Resveratrol Induces Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Neuron-Like Cells","volume":"2017","author":"Guo","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"74","DOI":"10.2174\/092986710789957760","article-title":"Design and development of nanovehicle-based delivery systems for preventive or therapeutic supplementation with flavonoids","volume":"17","author":"Leonarduzzi","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Testa, G., Gamba, P., Badilli, U., Gargiulo, S., Maina, M., Guina, T., Calfapietra, S., Biasi, F., Cavalli, R., and Poli, G. (2014). Loading into nanoparticles improves quercetin\u2019s efficacy in preventing neuroinflammation induced by oxysterols. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096795"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jconrel.2010.11.033","article-title":"Neurotherapeutic applications of nanoparticles in Alzheimer\u2019s disease","volume":"152","author":"Sahni","year":"2011","journal-title":"J. Control. Release"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"804","DOI":"10.3945\/an.117.016261","article-title":"Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function","volume":"8","author":"Poulose","year":"2017","journal-title":"Adv. Nutr."},{"key":"ref_23","first-page":"23","article-title":"Modulation of neurotrophic signaling pathways by polyphenols","volume":"10","author":"Moosavi","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12640-016-9600-1","article-title":"Impact of Plant-Derived Flavonoids on Neurodegenerative Diseases","volume":"30","author":"Costa","year":"2016","journal-title":"Neurotox. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0197-0186(96)00071-X","article-title":"Neurotrophins and their receptors in nerve injury and repair","volume":"30","author":"Ebadi","year":"1997","journal-title":"Neurochem. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/S0753-3322(02)00205-6","article-title":"Absorption and metabolism of polyphenols in the gut and impact on health","volume":"56","author":"Scalbert","year":"2002","journal-title":"Biomed. Pharmacother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11456","DOI":"10.1038\/s41598-017-11512-6","article-title":"Polyphenols journey through blood-brain barrier towards neuronal protection","volume":"7","author":"Figueira","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jphs.2014.12.015","article-title":"Nonpeptide neurotrophic agents useful in the treatment of neurodegenerative diseases such as Alzheimer\u2019s disease","volume":"127","author":"Akagi","year":"2015","journal-title":"J. Pharmacol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1007\/s12035-016-9924-0","article-title":"Delayed Treatment with green tea polyphenol egcg promotes neurogenesis after ischemic stroke in adult mice","volume":"54","author":"Zhang","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9651236","DOI":"10.1155\/2016\/9651236","article-title":"Resveratrol: A Potential Hippocampal Plasticity Enhancer","volume":"2016","author":"Dias","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S0254-6272(14)60018-2","article-title":"Parsley: A review of ethnopharmacology, phytochemistry and biological activities","volume":"33","author":"Farzaei","year":"2013","journal-title":"J. Tradit. Chin. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6","DOI":"10.2174\/18763960010030100006","article-title":"Antioxidant properties of honey and its role in preventing health disorders","volume":"3","author":"Khalil","year":"2010","journal-title":"Open Nutraceut. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.chroma.2016.12.020","article-title":"Olive oil polyphenols: A quantitative method by high-performance liquid-chromatography-diode-array detection for their determination and the assessment of the related health claim","volume":"1481","author":"Ricciutelli","year":"2017","journal-title":"J. Chromatogr. A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ejphar.2004.08.043","article-title":"Apigenin modulates GABAergic and glutamatergic transmission in cultured cortical neurons","volume":"502","author":"Losi","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"30451","DOI":"10.1016\/S0021-9258(18)43834-3","article-title":"Induction of cholinergic differentiation with neurite sprouting by de novo biosynthesis and expression of GD3 and b-series gangliosides in Neuro2a cells","volume":"269","author":"Kojima","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jneumeth.2009.11.004","article-title":"Differentiation of mouse Neuro 2A cells into dopamine neurons","volume":"186","author":"Tremblay","year":"2010","journal-title":"J. Neurosci. Methods"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0024-3205(91)90440-M","article-title":"Diazepam binding inhibitor (DBI): A peptide with multiple biological actions","volume":"49","author":"Costa","year":"1991","journal-title":"Life Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hamdi, Y., Kaddour, H., Vaudry, D., Bahdoudi, S., Douiri, S., Leprince, J., Castel, H., Vaudry, H., Tonon, M.C., and Amri, M. (2012). The octadecaneuropeptide ODN protects astrocytes against hydrogen peroxide-induced apoptosis via a PKA\/MAPK-dependent mechanism. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042498"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.pharmthera.2008.11.006","article-title":"VPAC and PAC receptors: From ligands to function","volume":"12","author":"Dickson","year":"2009","journal-title":"Pharmacol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1124\/pr.109.001370","article-title":"Pituitary adenylate cyclase activating polypeptide and its receptors: 20 years after the discovery","volume":"61","author":"Vaudry","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/j.1471-4159.2007.05018.x","article-title":"PACAP-38 induces neuronal differentiation of human SH-SY5Y neuroblastoma cells via cAMP-mediated activation of ERK and p38 MAP kinases","volume":"104","author":"Monaghan","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9749","DOI":"10.1074\/jbc.M109.043117","article-title":"Pituitary adenylate cyclase-activating polypeptide (PACAP)\/PAC1HOP1 receptor activation coordinates multiple neurotrophic signaling pathways: Akt activation through phosphatidylinositol 3-kinase gamma and vesicle endocytosis for neuronal survival","volume":"285","author":"May","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.yexcr.2013.11.003","article-title":"PACAP and VIP increase the expression of myelin-related proteins in rat schwannoma cells: Involvement of PAC1\/VPAC2 receptor-mediated activation of PI3K\/Akt signaling pathways","volume":"322","author":"Castorina","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s10194-018-0855-1","article-title":"Discovery of PACAP and its receptors in the brain","volume":"19","author":"Hirabayashi","year":"2018","journal-title":"J. Headache Pain"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7217","DOI":"10.1073\/pnas.0610068104","article-title":"Resveratrol stimulates AMP kinase activity in neurons","volume":"104","author":"Dasgupta","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.yexcr.2011.10.002","article-title":"The all-trans retinoic acid (atRA)-regulated gene Calmin (Clmn) regulates cell cycle exit and neurite outgrowth in murine neuroblastoma (Neuro2a) cells","volume":"318","author":"Marzinke","year":"2012","journal-title":"Exp. Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S0306-4522(96)00617-3","article-title":"Pituitary adenylate cyclase-activating polypeptide promotes cell survival and neurite outgrowth in rat cerebellar neuroblasts","volume":"78","author":"Gonzalez","year":"1997","journal-title":"Neuroscience"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1016\/j.peptides.2007.04.013","article-title":"Neurotrophic effects of PACAP in the cerebellar cortex","volume":"28","author":"Botia","year":"2007","journal-title":"Peptides"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ogata, K., Shintani, N., Hayata-Takano, A., Kamo, T., Higashi, S., Seiriki, K., Momosaki, H., Vaudry, D., Vaudry, H., and Galas, L. (2015). PACAP enhances axon outgrowth in cultured hippocampal neurons to a comparable extent as BDNF. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120526"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1111\/jnc.12140","article-title":"The octadecaneuropeptide ODN prevents 6-hydroxydopamine-induced apoptosis of cerebellar granule neurons through a PKC-MAPK-dependent pathway","volume":"125","author":"Kaddour","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1002\/mnfr.200700185","article-title":"Inhibitory effects of trans-resveratrol analogs molecules on the proliferation and the cell cycle progression of human colon tumoral cells","volume":"52","author":"Marel","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1016\/j.biochi.2008.06.006","article-title":"Antiproliferative activities of resveratrol and related compounds in human hepatocyte derived HepG2 cells are associated with biochemical cell disturbance revealed by fluorescence analyses","volume":"90","author":"Colin","year":"2008","journal-title":"Biochimie"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/1098-2744(200006)28:2<102::AID-MC6>3.0.CO;2-2","article-title":"Cell-cycle arrest at G2\/M and growth inhibition by apigenin in human colon carcinoma cell lines","volume":"28","author":"Wang","year":"2000","journal-title":"Mol. Carcinog."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.neulet.2004.10.087","article-title":"Ibuprofen and apigenin induce apoptosis and cell cycle arrest in activated microglia","volume":"375","author":"Elsisi","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_55","unstructured":"Latruffe, N. (2017). Vin, Nutrition M\u00e9diterran\u00e9enne et Sant\u00e9: Une Association Vertueuse, Editions Universitaires de Dijon, Collection Sciences."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00394-010-0102-2","article-title":"Effects of oxysterols on cell viability, inflammatory cytokines, VEGF, and reactive oxygen species production on human retinal cells: Cytoprotective effects and prevention of VEGF secretion by resveratrol","volume":"49","author":"Dugas","year":"2010","journal-title":"Eur. J. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1002\/jsfa.6228","article-title":"Effects of dietary phytophenols on the expression of microRNAs involved in mammalian cell homeostasis","volume":"93","author":"Michaille","year":"2013","journal-title":"J. Sci. Food Agric."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11010-015-2452-9","article-title":"Apigenin promotes osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways","volume":"407","author":"Zhang","year":"2015","journal-title":"Mol. Cell. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e12904","DOI":"10.1111\/eci.12904","article-title":"Effect of olive oil phenolic compounds on osteoblast differentiation","volume":"48","author":"Rivas","year":"2018","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"78300","DOI":"10.18632\/oncotarget.20962","article-title":"Apigenin enhances skeletal muscle hypertrophy and myoblast differentiation by regulating Prmt7","volume":"8","author":"Jang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s00394-011-0282-4","article-title":"Proteomic study of granulocytic differentiation induced by apigenin 7-glucoside in human promyelocytic leukemia HL-60 cells","volume":"52","author":"Nakazaki","year":"2013","journal-title":"Eur. J. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1006\/bbrc.1994.2498","article-title":"Apigenin induces morphological differentiation and G2-M arrest in rat neuronal cells","volume":"204","author":"Sato","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1097\/CAD.0000000000000413","article-title":"The flavonoid apigenin from Croton betulaster Mull inhibits proliferation, induces differentiation and regulates the inflammatory profile of glioma cells","volume":"27","author":"Coelho","year":"2016","journal-title":"Anticancer Drugs"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Jia, Y., Wang, N., and Liu, X. (2017). Resveratrol and Amyloid-Beta: Mechanistic Insights. Nutrients, 9.","DOI":"10.3390\/nu9101122"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kashyap, M.P., Roberts, C., Waseem, M., and Tyagi, P. (2018). Drug Targets in Neurotrophin Signaling in the Central and Peripheral Nervous System. Mol. Neurobiol.","DOI":"10.1007\/s12035-018-0885-3"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1007\/s00018-017-2727-2","article-title":"Neuroprotective effects of the gliopeptide ODN in an in vivo model of Parkinson\u2019s disease","volume":"75","author":"Bahdoudi","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1007\/s00216-010-3719-3","article-title":"A validated method for the quantification of curcumin in plasma and brain tissue by fast narrow-bore high-performance liquid chromatography with fluorescence detection","volume":"397","author":"Schiborr","year":"2010","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1039\/C4FO00817K","article-title":"Enhancement of flavonoid ability to cross the blood-brain barrier of rats by co-administration with \u03b1-tocopherol","volume":"6","author":"Ferri","year":"2015","journal-title":"Food Funct."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S1367-5931(03)00080-2","article-title":"The toxicogenomics of nuclear receptor agonists","volume":"7","author":"Ulrich","year":"2003","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1073\/pnas.64.1.316","article-title":"In vitro differentiation of a mouse neuroblastoma","volume":"64","author":"Schubert","year":"1969","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1073\/pnas.66.1.160","article-title":"Regulation of axon formation by clonal lines of a neural tumor","volume":"66","author":"Seeds","year":"1970","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1038\/sj.onc.1208494","article-title":"Signalling pathways leading to neuroblastoma differentiation after serum withdrawal: HDL blocks neuroblastoma differentiation by inhibition of EGFR","volume":"24","author":"Evangelopoulos","year":"2005","journal-title":"Oncogene"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.peptides.2015.06.010","article-title":"Octadecaneuropeptide ODN prevents hydrogen peroxide-induced oxidative damage of biomolecules in cultured rat astrocytes","volume":"71","author":"Hamdi","year":"2015","journal-title":"Peptides"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4596","DOI":"10.1007\/s12035-017-0630-3","article-title":"Endogenous Expression of ODN-Related Peptides in Astrocytes Contributes to Cell Protection against Oxidative Stress: Astrocyte-Neuron Crosstalk Relevance for Neuronal Survival","volume":"55","author":"Ghouili","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1007\/s11064-016-2150-3","article-title":"Role of cell metabolism and mitochondrial function during adult neurogenesis","volume":"42","author":"Almeida","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e1800051","DOI":"10.1002\/bies.201800051","article-title":"Dietary micronutrients promote neuronal differentiation by modulating the mitochondrial-nuclear dialogue","volume":"40","author":"Xie","year":"2018","journal-title":"Bioessays"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1177\/1352458514544537","article-title":"The central role of mitochondria in axonal degeneration in multiple sclerosis","volume":"20","author":"Campbell","year":"2014","journal-title":"Mult. Scler. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.abb.2014.05.017","article-title":"Polyphenols and mitochondria: An update on their increasingly emerging ROS-scavenging independent actions","volume":"559","author":"Ferreira","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.neuropharm.2015.08.028","article-title":"Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis","volume":"110","author":"Sedel","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1124\/mol.63.1.224","article-title":"All-trans-retinoic acid binds to and inhibits adenine nucleotide translocase and induces mitochondrial permeability transition","volume":"63","author":"Notario","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.neuropharm.2014.07.012","article-title":"Neuroprotective and neurotrophic effects of Apigenin and Luteolin in MPTP induced parkinsonism in mice","volume":"86","author":"Patil","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4421","DOI":"10.1039\/C7FO00991G","article-title":"Neuroprotective action of tea polyphenols on oxidative stress-induced apoptosis through the activation of the TrkB\/CREB\/BDNF pathway and Keap1\/Nrf2 signaling pathway in SH-SY5Y cells and mice brain","volume":"8","author":"Qi","year":"2017","journal-title":"Food Funct."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/6\/3\/67\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:13:39Z","timestamp":1760195619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/6\/3\/67"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,22]]},"references-count":82,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["diseases6030067"],"URL":"https:\/\/doi.org\/10.3390\/diseases6030067","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,22]]}}}