{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:56:19Z","timestamp":1789689379938,"version":"4.0.1"},"reference-count":39,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T00:00:00Z","timestamp":1662940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2021R1A2C1010091"],"award-info":[{"award-number":["NRF-2021R1A2C1010091"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["321036052HD020"],"award-info":[{"award-number":["321036052HD020"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003624","name":"Ministry of Agriculture, Food, and Rural Affairs","doi-asserted-by":"publisher","award":["NRF-2021R1A2C1010091"],"award-info":[{"award-number":["NRF-2021R1A2C1010091"]}],"id":[{"id":"10.13039\/501100003624","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003624","name":"Ministry of Agriculture, Food, and Rural Affairs","doi-asserted-by":"publisher","award":["321036052HD020"],"award-info":[{"award-number":["321036052HD020"]}],"id":[{"id":"10.13039\/501100003624","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurodegenerative diseases such as Parkinson\u2019s disease (PD) are known to be related to oxidative stress and neuroinflammation, and thus, modulating neuroinflammation offers a possible means of treating PD-associated pathologies. Morin (2\u2032,3,4\u2032,5,7-pentahydroxy flavone) is a flavonol with anti-oxidative and anti-inflammatory effects found in wines, herbs, and fruits. The present study was undertaken to determine whether a morin-containing diet has protective effects in an MPTP-induced mouse model of PD. Mice were fed a control or morin diet for 34 days, and then MPTP (30 mg\/kg, i.p.) was administered daily for 5 days to induce a PD-like pathology. We found that dietary morin prevented MPTP-induced motor dysfunction and ameliorated dopaminergic neuronal damage in striatum (STR) and substantia nigra (SN) in our mouse model. Furthermore, MPTP-induced neuroinflammation was significantly reduced in mice fed morin. In vitro studies showed that morin effectively suppressed glial activations in primary microglia and astrocytes, and biochemical analysis and a docking simulation indicated that the anti-inflammatory effects of morin were mediated by blocking the extracellular signal-regulated kinase (ERK)-p65 pathway. These findings suggest that morin effectively inhibits glial activations and has potential use as a functional food ingredient with therapeutic potential for the treatment of PD and other neurodegenerative diseases associated with neuroinflammation.<\/jats:p>","DOI":"10.3390\/ijms231810578","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T22:53:46Z","timestamp":1663023226000},"page":"10578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Anti-Inflammatory and Neuroprotective Effects of Morin in an MPTP-Induced Parkinson\u2019s Disease Model"],"prefix":"10.3390","volume":"23","author":[{"given":"Dong Geun","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seulah","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea"},{"name":"Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu 41062, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaehoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seonguk","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myunggyo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsook","family":"Ahn","sequence":"additional","affiliation":[{"name":"Center for Food and Bioconvergence, and Research Institute of Agriculture and Life Sciences, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9947-4032","authenticated-orcid":false,"given":"Haeseung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-9424","authenticated-orcid":false,"given":"Seung-Cheol","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Cogno-Mechatronics Engineering, College of Nanoscience and Nanotechnology, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4813-748X","authenticated-orcid":false,"given":"Nam-Chul","family":"Ha","sequence":"additional","affiliation":[{"name":"Center for Food and Bioconvergence, and Research Institute of Agriculture and Life Sciences, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3203-2130","authenticated-orcid":false,"given":"Jaewon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2741\/S415","article-title":"Parkinson\u2019s disease: A review","volume":"6","author":"Beitz","year":"2014","journal-title":"Front. Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/jnc.13691","article-title":"The clinical symptoms of Parkinson\u2019s disease","volume":"139","author":"Sveinbjornsdottir","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and Treatment of Parkinson Disease: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.molmed.2012.12.003","article-title":"Parkinson\u2019s disease in the nuclear age of neuroinflammation","volume":"19","author":"Nolan","year":"2013","journal-title":"Trends Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Miyazaki, I., and Asanuma, M. (2020). Neuron-Astrocyte Interactions in Parkinson\u2019s Disease. Cells, 9.","DOI":"10.3390\/cells9122623"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4784268","DOI":"10.1155\/2018\/4784268","article-title":"Linking Neuroinflammation and Neurodegeneration in Parkinson\u2019s Disease","volume":"2018","author":"Gelders","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrn2038","article-title":"Microglia-mediated neurotoxicity: Uncovering the molecular mechanisms","volume":"8","author":"Block","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/S1474-4422(09)70062-6","article-title":"Neuroinflammation in Parkinson\u2019s disease: A target for neuroprotection?","volume":"8","author":"Hirsch","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s12272-019-01133-0","article-title":"Significant roles of neuroinflammation in Parkinson\u2019s disease: Therapeutic targets for PD prevention","volume":"42","author":"Lee","year":"2019","journal-title":"Arch. Pharm. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lee, S., Hong, D.G., Yang, S., Kim, J., Baek, M., Kim, S., Thirumalai, D., Chung, H.Y., Chang, S.C., and Lee, J. (2022). Anti-Inflammatory Effect of IKK-Activated GSK-3beta Inhibitory Peptide Prevented Nigrostriatal Neurodegeneration in the Rodent Model of Parkinson\u2019s Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020998"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1002\/jnr.23307","article-title":"Baicalein attenuates astroglial activation in the 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson\u2019s disease model by downregulating the activations of nuclear factor-kappaB, ERK, and JNK","volume":"92","author":"Lee","year":"2014","journal-title":"J. Neurosci. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.brainres.2015.09.029","article-title":"Silibinin suppresses astroglial activation in a mouse model of acute Parkinson\u2019s disease by modulating the ERK and JNK signaling pathways","volume":"1627","author":"Lee","year":"2015","journal-title":"Brain Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"146642","DOI":"10.1016\/j.brainres.2019.146642","article-title":"Anti-inflammatory effects of usnic acid in an MPTP-induced mouse model of Parkinson\u2019s disease","volume":"1730","author":"Lee","year":"2020","journal-title":"Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lee, S., Suh, Y.J., Yang, S., Hong, D.G., Ishigami, A., Kim, H., Hur, J.S., Chang, S.C., and Lee, J. (2021). Neuroprotective and Anti-Inflammatory Effects of Evernic Acid in an MPTP-Induced Parkinson\u2019s Disease Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042098"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111511","DOI":"10.1016\/j.biopha.2021.111511","article-title":"Morin hydrate: A comprehensive review on novel natural dietary bioactive compound with versatile biological and pharmacological potential","volume":"138","author":"Rajput","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/978-3-319-41334-1_19","article-title":"Morin and Its Role in Chronic Diseases","volume":"928","author":"Sinha","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.nbd.2011.07.005","article-title":"Morin attenuates tau hyperphosphorylation by inhibiting GSK3beta","volume":"44","author":"Gong","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"774","DOI":"10.2174\/0929867323666160106150821","article-title":"Morin: A Promising Natural Drug","volume":"23","author":"Caselli","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.4110\/in.2020.20.e32","article-title":"Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice","volume":"20","author":"Hong","year":"2020","journal-title":"Immune Netw."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/jnr.23764","article-title":"Neuroprotective and anti-inflammatory effects of morin in a murine model of Parkinson\u2019s disease","volume":"94","author":"Lee","year":"2016","journal-title":"J. Neurosci. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pajares, M., AI, I.R., Manda, G., Bosca, L., and Cuadrado, A. (2020). Inflammation in Parkinson\u2019s Disease: Mechanisms and Therapeutic Implications. Cells, 9.","DOI":"10.3390\/cells9071687"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105028","DOI":"10.1016\/j.nbd.2020.105028","article-title":"Microglia and astrocyte dysfunction in parkinson\u2019s disease","volume":"144","author":"Kam","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40035-015-0042-0","article-title":"Neuroinflammation in Parkinson\u2019s disease and its potential as therapeutic target","volume":"4","author":"Wang","year":"2015","journal-title":"Transl. Neurodegener."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1007\/s11064-012-0751-z","article-title":"Acacetin attenuates neuroinflammation via regulation the response to LPS stimuli in vitro and in vivo","volume":"37","author":"Ha","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.fct.2018.03.011","article-title":"Effects of Paullinia cupana extract on lamotrigine pharmacokinetics in rats: A herb-drug interaction on the gastrointestinal tract with potential clinical impact","volume":"115","author":"Ventura","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.fct.2019.01.038","article-title":"Development of morin\/hydroxypropyl-beta-cyclodextrin inclusion complex: Enhancement of bioavailability, antihyperalgesic and anti-inflammatory effects","volume":"126","author":"Lima","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0021-9150(02)00067-9","article-title":"Serum non-esterified very long-chain PUFA are associated with markers of endothelial dysfunction","volume":"164","author":"Seljeflot","year":"2002","journal-title":"Atherosclerosis"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"633856","DOI":"10.3389\/fendo.2021.633856","article-title":"Lower Baseline Serum Triglyceride Levels Are Associated with Higher Decrease in Body Mass Index after Laparoscopy Sleeve Gastrectomy among Obese Patients","volume":"12","author":"Huang","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1159\/000484302","article-title":"Protective Effect of Curcumin Against Oxidative Stress-Induced Injury in Rats with Parkinson\u2019s Disease Through the Wnt\/ beta-Catenin Signaling Pathway","volume":"43","author":"Wang","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e13176","DOI":"10.1111\/jfbc.13176","article-title":"Antioxidant and anti-inflammatory effects of Lilium lancifolium bulbs extract","volume":"44","author":"Sim","year":"2020","journal-title":"J. Food Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lee, S., Suh, Y.J., Lee, Y., Yang, S., Hong, D.G., Thirumalai, D., Chang, S.C., Chung, K.W., Jung, Y.S., and Moon, H.R. (2021). Anti-Inflammatory Effects of the Novel Barbiturate Derivative MHY2699 in an MPTP-Induced Mouse Model of Parkinson\u2019s Disease. Antioxidants, 10.","DOI":"10.3390\/antiox10111855"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.phrs.2012.04.005","article-title":"ERK1\/2 MAP kinases: Structure, function, and regulation","volume":"66","author":"Roskoski","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"308461","DOI":"10.1155\/2015\/308461","article-title":"The interplay between cyclic AMP, MAPK, and NF-kappaB pathways in response to proinflammatory signals in microglia","volume":"2015","author":"Ghosh","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s00204-015-1472-2","article-title":"Compromised MAPK signaling in human diseases: An update","volume":"89","author":"Kim","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"462","DOI":"10.3389\/fphar.2018.00462","article-title":"The Anti-neuroinflammatory Activity of Tectorigenin Pretreatment via Downregulated NF-kappaB and ERK\/JNK Pathways in BV-2 Microglial and Microglia Inactivation in Mice with Lipopolysaccharide","volume":"9","author":"Lim","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.stem.2013.01.008","article-title":"Genetic correction of a LRRK2 mutation in human iPSCs links parkinsonian neurodegeneration to ERK-dependent changes in gene expression","volume":"12","author":"Reinhardt","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s00210-019-01804-1","article-title":"The protective effect of inosine against rotenone-induced Parkinson\u2019s disease in mice; role of oxido-nitrosative stress, ERK phosphorylation, and A2AR expression","volume":"393","author":"Kozman","year":"2020","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1158\/1535-7163.MCT-17-0456","article-title":"Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1\/2 Inhibitor BVD-523 (Ulixertinib)","volume":"16","author":"Germann","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.bbrc.2018.08.182","article-title":"Crystal structure of GSK3beta in complex with the flavonoid, morin","volume":"504","author":"Kim","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10578\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:30:02Z","timestamp":1760142602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10578"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,12]]},"references-count":39,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231810578"],"URL":"https:\/\/doi.org\/10.3390\/ijms231810578","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,12]]}}}