{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:58:13Z","timestamp":1793051893153,"version":"4.5.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T00:00:00Z","timestamp":1473292800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T00:00:00Z","timestamp":1473292800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["2R01NS064136"],"award-info":[{"award-number":["2R01NS064136"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81271274, 81471171"],"award-info":[{"award-number":["81271274, 81471171"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81301019"],"award-info":[{"award-number":["81301019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2016,12]]},"DOI":"10.1186\/s12974-016-0705-5","type":"journal-article","created":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T10:55:08Z","timestamp":1473332108000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Glycyrrhizin protects against focal cerebral ischemia via inhibition of T cell activity and HMGB1-mediated mechanisms"],"prefix":"10.1186","volume":"13","author":[{"given":"Xiaoxing","family":"Xiong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheri","family":"Krams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengmei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4180-653X","authenticated-orcid":false,"given":"Heng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,9,8]]},"reference":[{"key":"705_CR1","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1055\/s-2006-957625","volume":"63","author":"A Moon","year":"1997","unstructured":"Moon A, Kim SH. Effect of Glycyrrhiza glabra roots and glycyrrhizin on the glucuronidation in rats. Planta Med. 1997;63:115\u20139.","journal-title":"Planta Med"},{"key":"705_CR2","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s00535-009-0034-x","volume":"44","author":"N Tanaka","year":"2009","unstructured":"Tanaka N, Horiuchi A, Yamaura T, Komatsu M, Yokoyama T, Okaniwa S, Nagaya T, Yoshizawa K, Kiyosawa K, Aoyama T, Tanaka E. Efficacy and safety of addition of minor bloodletting (petit phlebotomy) in hepatitis C virus-infected patients receiving regular glycyrrhizin injections. J Gastroenterol. 2009;44:577\u201382.","journal-title":"J Gastroenterol"},{"key":"705_CR3","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.cyto.2006.10.002","volume":"35","author":"M Takei","year":"2006","unstructured":"Takei M, Kobayashi M, Herndon DN, Pollard RB, Suzuki F. Glycyrrhizin inhibits the manifestations of anti-inflammatory responses that appear in association with systemic inflammatory response syndrome (SIRS)-like reactions. Cytokine. 2006;35:295\u2013301.","journal-title":"Cytokine"},{"key":"705_CR4","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1016\/j.intimp.2010.07.004","volume":"10","author":"JR Shi","year":"2010","unstructured":"Shi JR, Mao LG, Jiang RA, Qian Y, Tang HF, Chen JQ. Monoammonium glycyrrhizinate inhibited the inflammation of LPS-induced acute lung injury in mice. Int Immunopharmacol. 2010;10:1235\u201341.","journal-title":"Int Immunopharmacol"},{"key":"705_CR5","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1111\/j.1745-7254.2006.00346.x","volume":"27","author":"IK Hwang","year":"2006","unstructured":"Hwang IK, Lim SS, Choi KH, Yoo KY, Shin HK, Kim EJ, Yoon-Park JH, Kang TC, Kim YS, Kwon DY, et al. Neuroprotective effects of roasted licorice, not raw form, on neuronal injury in gerbil hippocampus after transient forebrain ischemia. Acta Pharmacol Sin. 2006;27:959\u201365.","journal-title":"Acta Pharmacol Sin"},{"key":"705_CR6","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.neuropharm.2011.06.026","volume":"61","author":"M Ohnishi","year":"2011","unstructured":"Ohnishi M, Katsuki H, Fukutomi C, Takahashi M, Motomura M, Fukunaga M, Matsuoka Y, Isohama Y, Izumi Y, Kume T, et al. HMGB1 inhibitor glycyrrhizin attenuates intracerebral hemorrhage-induced injury in rats. Neuropharmacology. 2011;61:975\u201380.","journal-title":"Neuropharmacology"},{"key":"705_CR7","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.nbd.2011.12.056","volume":"46","author":"SW Kim","year":"2012","unstructured":"Kim SW, Jin Y, Shin JH, Kim ID, Lee HK, Park S, Han PL, Lee JK. Glycyrrhizic acid affords robust neuroprotection in the postischemic brain via anti-inflammatory effect by inhibiting HMGB1 phosphorylation and secretion. Neurobiol Dis. 2012;46:147\u201356.","journal-title":"Neurobiol Dis"},{"key":"705_CR8","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1038\/sj.jcbfm.9600482","volume":"27","author":"PD Hurn","year":"2007","unstructured":"Hurn PD, Subramanian S, Parker SM, Afentoulis ME, Kaler LJ, Vandenbark AA, Offner H. T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab. 2007;27:1798\u2013805.","journal-title":"J Cereb Blood Flow Metab"},{"key":"705_CR9","doi-asserted-by":"crossref","unstructured":"Xiong X, Gu L, Zhang H, Xu B, Zhu S, Zhao H. The protective effects of T cell deficiency against brain injury are ischemic model-dependent in rats. Neurochem Int. 2013;62:265\u201370.","DOI":"10.1016\/j.neuint.2012.11.016"},{"key":"705_CR10","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1016\/j.intimp.2007.05.011","volume":"7","author":"C Feng","year":"2007","unstructured":"Feng C, Wang H, Yao C, Zhang J, Tian Z. Diammonium glycyrrhizinate, a component of traditional Chinese medicine Gan-Cao, prevents murine T-cell-mediated fulminant hepatitis in IL-10- and IL-6-dependent manners. Int Immunopharmacol. 2007;7:1292\u20138.","journal-title":"Int Immunopharmacol"},{"key":"705_CR11","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1038\/sj.jcbfm.9600582","volume":"28","author":"J Qiu","year":"2008","unstructured":"Qiu J, Nishimura M, Wang Y, Sims JR, Qiu S, Savitz SI, Salomone S, Moskowitz MA. Early release of HMGB-1 from neurons after the onset of brain ischemia. J Cereb Blood Flow Metab. 2008;28:927\u201338.","journal-title":"J Cereb Blood Flow Metab"},{"key":"705_CR12","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1097\/01.shk.0000209540.99176.72","volume":"25","author":"RS Goldstein","year":"2006","unstructured":"Goldstein RS, Gallowitsch-Puerta M, Yang L, Rosas-Ballina M, Huston JM, Czura CJ, Lee DC, Ward MF, Bruchfeld AN, Wang H, et al. Elevated high-mobility group box 1 levels in patients with cerebral and myocardial ischemia. Shock. 2006;25:571\u20134.","journal-title":"Shock"},{"key":"705_CR13","doi-asserted-by":"publisher","first-page":"12023","DOI":"10.1523\/JNEUROSCI.2435-08.2008","volume":"28","author":"S Muhammad","year":"2008","unstructured":"Muhammad S, Barakat W, Stoyanov S, Murikinati S, Yang H, Tracey KJ, Bendszus M, Rossetti G, Nawroth PP, Bierhaus A, Schwaninger M. The HMGB1 receptor RAGE mediates ischemic brain damage. J Neurosci. 2008;28:12023\u201331.","journal-title":"J Neurosci"},{"key":"705_CR14","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1097\/SHK.0b013e3181834070","volume":"31","author":"LF Huang","year":"2009","unstructured":"Huang LF, Yao YM, Zhang LT, Dong N, Yu Y, Sheng ZY. The effect of high-mobility group box 1 protein on activity of regulatory T cells after thermal injury in rats. Shock. 2009;31:322\u20139.","journal-title":"Shock"},{"key":"705_CR15","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1097\/SHK.0b013e3181672495","volume":"30","author":"LT Zhang","year":"2008","unstructured":"Zhang LT, Yao YM, Dong YQ, Dong N, Yu Y, Sheng ZY. Relationship between high-mobility group box 1 protein release and T-cell suppression in rats after thermal injury. Shock. 2008;30:449\u201355.","journal-title":"Shock"},{"key":"705_CR16","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.chembiol.2007.03.007","volume":"14","author":"L Mollica","year":"2007","unstructured":"Mollica L, De Marchis F, Spitaleri A, Dallacosta C, Pennacchini D, Zamai M, Agresti A, Trisciuoglio L, Musco G, Bianchi ME. Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities. Chem Biol. 2007;14:431\u201341.","journal-title":"Chem Biol"},{"key":"705_CR17","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1161\/STROKEAHA.110.593772","volume":"42","author":"X Xiong","year":"2011","unstructured":"Xiong X, Barreto GE, Xu L, Ouyang YB, Xie X, Giffard RG. Increased brain injury and worsened neurological outcome in interleukin-4 knockout mice after transient focal cerebral ischemia. Stroke. 2011;42:2026\u201332.","journal-title":"Stroke"},{"key":"705_CR18","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1161\/STROKEAHA.112.656611","volume":"43","author":"L Gu","year":"2012","unstructured":"Gu L, Xiong X, Zhang H, Xu B, Steinberg GK, Zhao H. Distinctive effects of T cell subsets in neuronal injury induced by cocultured splenocytes in vitro and by in vivo stroke in mice. Stroke. 2012;43:1941\u20136.","journal-title":"Stroke"},{"key":"705_CR19","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1002\/glia.20985","volume":"58","author":"L Xu","year":"2010","unstructured":"Xu L, Emery JF, Ouyang YB, Voloboueva LA, Giffard RG. Astrocyte targeted overexpression of Hsp72 or SOD2 reduces neuronal vulnerability to forebrain ischemia. Glia. 2010;58:1042\u20139.","journal-title":"Glia"},{"key":"705_CR20","doi-asserted-by":"publisher","first-page":"9794","DOI":"10.1523\/JNEUROSCI.3163-05.2005","volume":"25","author":"H Zhao","year":"2005","unstructured":"Zhao H, Shimohata T, Wang JQ, Sun G, Schaal DW, Sapolsky RM, Steinberg GK. Akt contributes to neuroprotection by hypothermia against cerebral ischemia in rats. J Neurosci. 2005;25:9794\u2013806.","journal-title":"J Neurosci"},{"key":"705_CR21","first-page":"205","volume":"10","author":"A Torabi","year":"2013","unstructured":"Torabi A, Tahmoorespur M, Vahedi F, Mosavari N, Nassiri M. Quantiation of IL-4, IL-10 and IFN-gamma genes expression after immunization of mice with CFP-10 and ESAT-6 containing vectors. Iran J Immunol. 2013;10:205\u201315.","journal-title":"Iran J Immunol"},{"key":"705_CR22","doi-asserted-by":"publisher","first-page":"471","DOI":"10.4049\/jimmunol.1003003","volume":"186","author":"JK Lim","year":"2011","unstructured":"Lim JK, Obara CJ, Rivollier A, Pletnev AG, Kelsall BL, Murphy PM. Chemokine receptor Ccr2 is critical for monocyte accumulation and survival in West Nile virus encephalitis. J Immunol. 2011;186:471\u20138.","journal-title":"J Immunol"},{"key":"705_CR23","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.ejphar.2013.12.032","volume":"724","author":"W Barakat","year":"2014","unstructured":"Barakat W, Safwet N, El-Maraghy NN, Zakaria MN. Candesartan and glycyrrhizin ameliorate ischemic brain damage through downregulation of the TLR signaling cascade. Eur J Pharmacol. 2014;724:43\u201350.","journal-title":"Eur J Pharmacol"},{"key":"705_CR24","doi-asserted-by":"publisher","first-page":"2679","DOI":"10.1002\/stem.1754","volume":"32","author":"C Chen","year":"2014","unstructured":"Chen C, Lin X, Wang J, Tang G, Mu Z, Chen X, Xu J, Wang Y, Zhang Z, Yang GY. Effect of HMGB1 on the paracrine action of EPC promotes post-ischemic neovascularization in mice. Stem Cells. 2014;32:2679\u201389.","journal-title":"Stem Cells"},{"key":"705_CR25","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.brainres.2013.08.057","volume":"1535","author":"J Huang","year":"2013","unstructured":"Huang J, Liu B, Yang C, Chen H, Eunice D, Yuan Z. Acute hyperglycemia worsens ischemic stroke-induced brain damage via high mobility group box-1 in rats. Brain Res. 2013;1535:148\u201355.","journal-title":"Brain Res"},{"key":"705_CR26","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1016\/j.neurobiolaging.2014.12.029","volume":"36","author":"H Wu","year":"2015","unstructured":"Wu H, Wu T, Hua W, Dong X, Gao Y, Zhao X, Chen W, Cao W, Yang Q, Qi J, et al. PGE2 receptor agonist misoprostol protects brain against intracerebral hemorrhage in mice. Neurobiol Aging. 2015;36:1439\u201350.","journal-title":"Neurobiol Aging"},{"key":"705_CR27","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.brainres.2014.07.002","volume":"1582","author":"J Zhang","year":"2014","unstructured":"Zhang J, Wu Y, Weng Z, Zhou T, Feng T, Lin Y. Glycyrrhizin protects brain against ischemia-reperfusion injury in mice through HMGB1-TLR4-IL-17A signaling pathway. Brain Res. 2014;1582:176\u201386.","journal-title":"Brain Res"},{"key":"705_CR28","doi-asserted-by":"publisher","first-page":"3835","DOI":"10.1182\/blood-2009-10-249078","volume":"115","author":"C Kleinschnitz","year":"2010","unstructured":"Kleinschnitz C, Schwab N, Kraft P, Hagedorn I, Dreykluft A, Schwarz T, Austinat M, Nieswandt B, Wiendl H, Stoll G. Early detrimental T-cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor thrombus formation. Blood. 2010;115:3835\u201342.","journal-title":"Blood"},{"key":"705_CR29","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1161\/CIRCULATIONAHA.105.593046","volume":"113","author":"G Yilmaz","year":"2006","unstructured":"Yilmaz G, Arumugam TV, Stokes KY, Granger DN. Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation. 2006;113:2105\u201312.","journal-title":"Circulation"},{"key":"705_CR30","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/nm.1927","volume":"15","author":"A Liesz","year":"2009","unstructured":"Liesz A, Suri-Payer E, Veltkamp C, Doerr H, Sommer C, Rivest S, Giese T, Veltkamp R. Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med. 2009;15:192\u20139.","journal-title":"Nat Med"},{"key":"705_CR31","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/nm.2399","volume":"17","author":"C Iadecola","year":"2011","unstructured":"Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med. 2011;17:796\u2013808.","journal-title":"Nat Med"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-016-0705-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12974-016-0705-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-016-0705-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T07:09:29Z","timestamp":1589526569000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-016-0705-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,8]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["705"],"URL":"https:\/\/doi.org\/10.1186\/s12974-016-0705-5","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,8]]},"assertion":[{"value":"31 March 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"241"}}