{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:55:41Z","timestamp":1790618141396,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260781"],"award-info":[{"award-number":["82260781"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018555","name":"Science and Technology Program of Guizhou Province","doi-asserted-by":"publisher","award":["QKH [2020]4Y192"],"award-info":[{"award-number":["QKH [2020]4Y192"]}],"id":[{"id":"10.13039\/501100018555","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018555","name":"Science and Technology Program of Guizhou Province","doi-asserted-by":"publisher","award":["QKH [ZK2023]549"],"award-info":[{"award-number":["QKH [ZK2023]549"]}],"id":[{"id":"10.13039\/501100018555","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018555","name":"Science and Technology Program of Guizhou Province","doi-asserted-by":"publisher","award":["QKH[2019]5406"],"award-info":[{"award-number":["QKH[2019]5406"]}],"id":[{"id":"10.13039\/501100018555","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270848"],"award-info":[{"award-number":["32270848"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Blood\u2013brain barrier (BBB) breakdown is one of the crucial pathological changes of cerebral ischaemia\u2013reperfusion (I\/R) injury. Trilobatin (TLB), a naturally occurring food additive, exerts neuroprotective effects against cerebral I\/R injury as demonstrated in our previous study. This study was designed to investigate the effect of TLB on BBB disruption after cerebral I\/R injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Rats with focal cerebral ischaemia caused by transient middle cerebral artery occlusion were studied along with brain microvascular endothelial cells and human astrocytes to mimic BBB injury caused by oxygen and glucose deprivation\/reoxygenation (OGD\/R).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The results showed that TLB effectively maintained BBB integrity and inhibited neuronal loss following cerebral I\/R challenge. Furthermore, TLB increased tight junction proteins including ZO\u20101, Occludin and Claudin 5, and decreased the levels of apolipoprotein E (APOE) 4, cyclophilin A (CypA) and phosphorylated nuclear factor kappa B (NF\u2010\u03baB), thereby reducing proinflammatory cytokines. TLB also decreased the Bax\/Bcl\u20102 ratio and cleaved\u2010caspase 3 levels along with a reduced number of apoptotic neurons. Molecular docking and transcriptomics predicted MMP9 as a prominent gene evoked by TLB treatment. The protective effects of TLB on cerebral I\/R\u2010induced BBB breakdown was largely abolished by overexpression of MMP9, and the beneficial effects of TLB on OGD\/R\u2010induced loss of BBB integrity in human brain microvascular endothelial cells and astrocyte co\u2010cultures was markedly reinforced by knockdown of MMP9.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our findings reveal a novel property of TLB: preventing BBB disruption following cerebral I\/R via targeting MMP9 and inhibiting APOE4\/CypA\/NF\u2010\u03baB axis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16239","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T05:24:14Z","timestamp":1695101054000},"page":"1005-1027","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Trilobatin attenuates cerebral ischaemia\/reperfusion\u2010induced blood\u2013brain barrier dysfunction by targeting matrix metalloproteinase 9: The legend of a food additive"],"prefix":"10.1111","volume":"181","author":[{"given":"Linying","family":"Feng","sequence":"first","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine Macau University of Science and Technology  Macau SAR China"},{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University  Zunyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeli","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine Macau University of Science and Technology  Macau SAR China"},{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University  Zunyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine Macau University of Science and Technology  Macau SAR China"},{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University  Zunyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianyou","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine Macau University of Science and Technology  Macau SAR China"},{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University  Zunyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunmei","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine Macau University of Science and Technology  Macau SAR China"},{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University  Zunyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuandong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University  Zunyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixu","family":"He","sequence":"additional","affiliation":[{"name":"The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University  Zunyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihai","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine Macau University of Science and Technology  Macau SAR China"},{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University  Zunyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-8041","authenticated-orcid":false,"given":"Zhu Yi","family":"Zhun","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine Macau University of Science and Technology  Macau SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmei","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine Macau University of Science and Technology  Macau SAR China"},{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University  Zunyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15541"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-021-01509-9"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111200"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-22-3489"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11087"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13324"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009759"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-021-00900-w"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2110097119"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4309"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.01.030"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00584"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.01.001"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-021-00483-2"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2014.06.022"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1125412"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00537-2"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2019.7825"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00267"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14912"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15961"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-022-00888-5"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.031410"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16629976"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-022-00495-6"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.841544"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11061199"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8360"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.174978"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105027"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202013076"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.02.008"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.04.022"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153660"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02533-8"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-020-0409-3"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0249-5"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2352-17.2018"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.05.077"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2247-3"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.028814"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000946"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.036104"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20202207"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15732"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15193"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.038483"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-01093-3"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-0996-2"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2020.1830363"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14611"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.05.017"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2017.05.003"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20291"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-020-00789-x"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2020.04.001"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.913367"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.721156"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.05.001"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106332"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101654RR"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202105442"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14102"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74519"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.16239","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T05:05:57Z","timestamp":1710133557000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.16239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,10]]},"references-count":68,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/bph.16239"],"URL":"https:\/\/doi.org\/10.1111\/bph.16239","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,10]]},"assertion":[{"value":"2023-02-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}