{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:53:33Z","timestamp":1788382413240,"version":"build-2803163510"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.nationalarchives.gov.uk\/doc\/open-government-licence\/version\/3\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Regulation of microglia polarisation may be a new way to treat ischaemic stroke based on its effects on brain injury. Isoliquiritigenin (ILG) is a flavonoid with neuroprotective function. The study investigated whether ILG regulated microglial polarisation and affects brain injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Here, a transient middle cerebral artery occlusion (tMCAO) model in vivo and lipopolysaccharide (LPS)-induced BV2 cells in vitro were established. Brain damage was assessed using a 2,3,5-triphenyl-tetrazolium-chloride staining assay. Microglial polarisation was analysed using enzyme linked immunosorbent assay, quantitative real-time polymerase chain reaction, and immunofluorescence assay. The levels of p38\/MAPK pathway-related factors were measured by western blot.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>ILG suppressed infarct volume and neurological function of tMCAO rats. Moreover, ILG facilitated M2 microglia polarisation and suppressed M1 polarisation in the tMCAO model and LPS-induced BV2 cells. Moreover, ILG reduced the phosphorylation of p38, MAPK activated protein kinase 2, and heat shock protein 27 induced by LPS. Rescue study showed that activating the p38\/MAPK pathway reversed the microglia polarisation induced by ILG and inactivating the p38\/MAPK pathway enchanced the microglia polarisation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>ILG promoted microglia M2 polarisation by inactivating the p38\/MAPK pathway, suggesting that ILG has the potential for the treatment of ischaemic stroke.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgad027","type":"journal-article","created":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T16:48:50Z","timestamp":1680886130000},"page":"828-836","source":"Crossref","is-referenced-by-count":15,"title":["Isoliquiritigenin regulates microglial M1\/M2 polarisation by mediating the P38\/MAPK pathway in cerebral stroke"],"prefix":"10.1093","volume":"75","author":[{"given":"Ruixia","family":"Wang","sequence":"first","affiliation":[{"name":"The Department of Neurology, The 983rd Hospital of Joint Logistic Support Force , Tianjin City ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8496-3594","authenticated-orcid":false,"given":"Weili","family":"Zhang","sequence":"additional","affiliation":[{"name":"Training Center, The 980th Hospital of Joint Logistic Support Force , Shijiazhuang City ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,1]]},"reference":[{"key":"2024103012242891400_CIT0001","doi-asserted-by":"crossref","first-page":"174638","DOI":"10.1016\/j.ejphar.2021.174638","article-title":"Biotechnology-based therapeutics for management of cerebral stroke","volume":"913","author":"Patel","year":"2021","journal-title":"Eur J Pharmacol"},{"key":"2024103012242891400_CIT0002","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0140-6736(20)31179-X","volume":"396","author":"Campbell","year":"2020","journal-title":"Lancet"},{"key":"2024103012242891400_CIT0003","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/ene.13409","article-title":"Ischaemic stroke","volume":"25","author":"Meschia","year":"2018","journal-title":"Eur J Neurol"},{"key":"2024103012242891400_CIT0004","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s13311-016-0483-x","article-title":"Inflammation and stroke: an overview","volume":"13","author":"Anrather","year":"2016","journal-title":"Neurotherapeutics"},{"key":"2024103012242891400_CIT0005","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1007\/s12265-013-9508-6","article-title":"Role of inflammation and its mediators in acute ischemic stroke","volume":"6","author":"Jin","year":"2013","journal-title":"J Cardiovasc Transl Res"},{"key":"2024103012242891400_CIT0006","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1146\/annurev-immunol-032713-120240","article-title":"Microglia development and function","volume":"32","author":"Nayak","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"2024103012242891400_CIT0007","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","article-title":"Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes","volume":"9","author":"Kwon","year":"2020","journal-title":"Transl Neurodegener"},{"key":"2024103012242891400_CIT0008","first-page":"2006","article-title":"Modulators of microglia activation and polarization in ischemic stroke (Review)","volume":"21","author":"Jiang","year":"2020","journal-title":"Mol Med Rep"},{"issue":"10","key":"2024103012242891400_CIT0009","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.3390\/ijms18102135","article-title":"Microglia and monocytes\/macrophages polarization reveal novel therapeutic mechanism against stroke","volume":"18","author":"Kanazawa","year":"2017","journal-title":"Int J Mol Sci"},{"key":"2024103012242891400_CIT0010","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1002\/ptr.5348","article-title":"A review: the pharmacology of isoliquiritigenin","volume":"29","author":"Peng","year":"2015","journal-title":"Phytother Res"},{"key":"2024103012242891400_CIT0011","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1007\/s10753-018-0777-8","article-title":"Protective effects of isoliquiritigenin on LPS-induced acute lung injury by activating PPAR-\u03b3","volume":"41","author":"Zhang","year":"2018","journal-title":"Inflammation"},{"key":"2024103012242891400_CIT0012","doi-asserted-by":"crossref","first-page":"23528","DOI":"10.1038\/s41598-021-02843-6","article-title":"Isoliquiritigenin, a potent human monoamine oxidase inhibitor, modulates dopamine D1, D3, and vasopressin V1A receptors","volume":"11","author":"Prajapati","year":"2021","journal-title":"Sci Rep"},{"key":"2024103012242891400_CIT0013","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.phrs.2005.12.008","article-title":"Protective effects of isoliquiritigenin in transient middle cerebral artery occlusion-induced focal cerebral ischemia in rats","volume":"53","author":"Zhan","year":"2006","journal-title":"Pharmacol Res"},{"key":"2024103012242891400_CIT0014","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/s41419-020-03186-2","article-title":"YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA","volume":"11","author":"Zhang","year":"2020","journal-title":"Cell Death Dis"},{"key":"2024103012242891400_CIT0015","doi-asserted-by":"crossref","first-page":"104795","DOI":"10.1016\/j.phrs.2020.104795","article-title":"Nose to brain drug delivery - A promising strategy for active components from herbal medicine for treating cerebral ischemia reperfusion","volume":"159","author":"Long","year":"2020","journal-title":"Pharmacol Res"},{"key":"2024103012242891400_CIT0016","doi-asserted-by":"crossref","first-page":"348","DOI":"10.3389\/fnagi.2018.00348","article-title":"Phytochemical and pharmacological role of Liquiritigenin and Isoliquiritigenin from radix Glycyrrhizae in human health and disease models","volume":"10","author":"Ramalingam","year":"2018","journal-title":"Front Aging Neurosci"},{"key":"2024103012242891400_CIT0017","doi-asserted-by":"crossref","first-page":"e1800147","DOI":"10.1002\/mnfr.201800147","article-title":"Regulatory roles of Flavonoids on Inflammasome activation during inflammatory responses","volume":"62","author":"Yi","year":"2018","journal-title":"Mol Nutr Food Res"},{"key":"2024103012242891400_CIT0018","doi-asserted-by":"crossref","first-page":"37253725","DOI":"10.3390\/molecules24203725","article-title":"Isoliquiritigenin inhibits ovarian cancer metastasis by reversing epithelial-to-Mesenchymal transition","volume":"24","author":"Chen","year":"2019","journal-title":"Molecules"},{"key":"2024103012242891400_CIT0019","doi-asserted-by":"crossref","first-page":"114528","DOI":"10.1016\/j.jpba.2021.114528","article-title":"Cell membrane-coated biomimetic magnetic nanoparticles for the bio-specific extraction of components from Gualou Guizhi decoction exhibiting activities against oxygen-glucose deprivation\/reperfusion injury","volume":"209","author":"He","year":"2022","journal-title":"J Pharm Biomed Anal"},{"key":"2024103012242891400_CIT0020","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.3892\/mmr.2015.3520","article-title":"Blood-brain barrier permeability of Gualou Guizhi granules and neuroprotective effects in ischemia\/reperfusion injury","volume":"12","author":"Li","year":"2015","journal-title":"Mol Med Rep"},{"key":"2024103012242891400_CIT0021","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.2147\/IJN.S368528","article-title":"Long-circulation and brain targeted Isoliquiritigenin micelle Nanoparticles: formation, characterization, tissue distribution, pharmacokinetics and effects for ischemic stroke","volume":"17","author":"Song","year":"2022","journal-title":"Int J Nanomedicine"},{"key":"2024103012242891400_CIT0022","doi-asserted-by":"crossref","first-page":"466","DOI":"10.14336\/AD.2020.0701","article-title":"Microglial polarization: novel therapeutic strategy against ischemic stroke","volume":"12","author":"Xue","year":"2021","journal-title":"Aging Dis"},{"key":"2024103012242891400_CIT0023","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nrneurol.2017.69","article-title":"Modulators of microglial activation and polarization after intracerebral haemorrhage","volume":"13","author":"Lan","year":"2017","journal-title":"Nat Rev Neurol"},{"key":"2024103012242891400_CIT0024","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrneurol.2014.207","article-title":"Microglial and macrophage polarization\u2014new prospects for brain repair","volume":"11","author":"Hu","year":"2015","journal-title":"Nat Rev Neurol"},{"key":"2024103012242891400_CIT0025","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.intimp.2016.08.037","article-title":"Methionine enkephalin regulates microglia polarization and function","volume":"40","author":"Xu","year":"2016","journal-title":"Int Immunopharmacol"},{"key":"2024103012242891400_CIT0026","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.neuroscience.2016.03.031","article-title":"Enhanced immune response to MMP3 stimulation in microglia expressing mutant huntingtin","volume":"325","author":"Connolly","year":"2016","journal-title":"Neuroscience"},{"key":"2024103012242891400_CIT0027","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.biopha.2018.05.143","article-title":"Treatment targets for M2 microglia polarization in ischemic stroke","volume":"105","author":"Wang","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"2024103012242891400_CIT0028","doi-asserted-by":"crossref","first-page":"105043","DOI":"10.1016\/j.bioorg.2021.105043","article-title":"Discovery of isoliquiritigenin analogues that reverse acute hepatitis by inhibiting macrophage polarization","volume":"114","author":"Yang","year":"2021","journal-title":"Bioorg Chem"},{"key":"2024103012242891400_CIT0029","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.taap.2014.07.001","article-title":"Isoliquiritigenin, a flavonoid from licorice, blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE2 and IL-6","volume":"279","author":"Zhao","year":"2014","journal-title":"Toxicol Appl Pharmacol"},{"key":"2024103012242891400_CIT0030","doi-asserted-by":"crossref","first-page":"108360","DOI":"10.1016\/j.intimp.2021.108360","article-title":"Effective-compound combination inhibits the M2-like polarization of macrophages and attenuates the development of pulmonary fibrosis by increasing autophagy through mTOR signaling","volume":"101","author":"Zhao","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"2024103012242891400_CIT0031","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.brainresbull.2020.02.015","article-title":"GYY4137 protects against MCAO via p38 MAPK mediated anti-apoptotic signaling pathways in rats","volume":"158","author":"Han","year":"2020","journal-title":"Brain Res Bull"},{"key":"2024103012242891400_CIT0032","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.brainres.2014.01.013","article-title":"Involvement of p38 MAPK in reactive astrogliosis induced by ischemic stroke","volume":"1551","author":"Roy Choudhury","year":"2014","journal-title":"Brain Res"},{"key":"2024103012242891400_CIT0033","doi-asserted-by":"crossref","first-page":"512","DOI":"10.3390\/biom9100512","article-title":"HMGB1-triggered inflammation inhibition of notoginseng leaf triterpenes against cerebral ischemia and reperfusion injury via MAPK and NF-\u03baB signaling pathways","volume":"9","author":"Xie","year":"2019","journal-title":"Biomolecules"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/75\/6\/828\/60220622\/rgad027.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/75\/6\/828\/60220622\/rgad027.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T17:22:34Z","timestamp":1730308954000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/75\/6\/828\/7110905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,1]]},"references-count":33,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6,1]]},"published-print":{"date-parts":[[2023,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgad027","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,6,1]]},"published":{"date-parts":[[2023,6,1]]}}}