{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:47:43Z","timestamp":1790304463085,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Ligustrazine (LSZ), an ingredient of <jats:italic>Ligusticum chuanxiong<\/jats:italic>, has long been used to treat neurovascular diseases in China. This study investigates its protective effects for the impairment of the blood\u2013brain barrier (BBB) and the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, the impacts of LSZ on the BBB function were firstly assessed in b. End3 cells in\u00a0vitro. Oxygen\u2013glucose deprivation (OGD) served as an injury factor and western blot (WB) analyzed the expressions of occludin and ZO\u20101, two tight junction proteins (TJs), essential for maintaining the integrity of the BBB. After bioinformatics analysis of the transcriptome in\u00a0vivo, qRT\u2010PCR of miR\u2010297c\u20105p was conducted and a dual\u2010luciferase reporter assay was used to verify the target protein, occludin, which was confirmed by hippocampal insertion using guide cannulas and microinfection of RNA oligos.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 3\u2010h deprivation of OGD of b. End3 cells resulted in noticeable reductions in the level of occludin and ZO\u20101. However, administration of LSZ (0.1\u2009\u03bcM) effectively restored these decreases. In normal mice, administration of LSZ (25\u2009mg\/kg, i.p., once daily for 9\u2009days) resulted in a notable reduction in miR\u2010297c\u20105p. In the middle cerebral artery occlusion (MCAO) mouse model, increased miR\u2010297c\u20105p was also reversed by LSZ administration. Bioinformatics analysis revealed one of the targets of miR\u2010297c\u20105p includes occludin. MiR\u2010297c\u20105p was found to directly target occludin in the dual\u2010luciferase reporter assay. Transfection of miR\u2010297c\u20105p agomir into b. End3 cells resulted in a significant reduction in the level of occludin, while transfection of antagomir led to an increase in occludin. Besides, stereotaxic injection of AAV\u2010miR\u2010297c\u20105p into the hippocampus reduced occludin level in\u00a0vivo. Ultimately, hippocampal microinfection of RNA oligos provided a confirmation that miR\u2010297c\u20105p was downregulated by LSZ in MCAO mice with up\u2010regulated occludin expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, the present findings provide new insights into regulating occludin by LSZ through downregulation of miR\u2010297c\u20105p.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70367","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T06:25:55Z","timestamp":1747981555000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ligustrazine Alleviates Blood\u2013Brain Barrier Damage by Downregulating Expression of <scp>miR<\/scp>\u2010297c\u20105p"],"prefix":"10.1111","volume":"31","author":[{"given":"Shaoyu","family":"Guan","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Research Division, Department of Pharmacy Medical Supplies Centre of PLA General Hospital\/Medical School of Chinese PLA  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruichen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Beijing University of Chinese Medicine  Beijing China"},{"name":"Department of Orthopaedics China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology The Seventh Medical Center of Chinese PLA General Hospital\/Medical School of Chinese PLA  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Sixth Medical Centre, Chinese PLA General Hospital\/Medical School of Chinese PLA  Beijing 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