{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:42:46Z","timestamp":1789389766992,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,12,16]],"date-time":"2017-12-16T00:00:00Z","timestamp":1513382400000},"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":["81273588"],"award-info":[{"award-number":["81273588"]}],"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":["81473274"],"award-info":[{"award-number":["81473274"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this study was to examine the comprehensive neuroprotective mechanism of ligustrazine, which is extracted from <jats:italic>Ligusticum Chuanxiong Hort<\/jats:italic>., against vascular dementia (VD) in rats and apoptosis in oxygen and glucose deprivation (OGD) PC12 cells. Rats were subjected to bilateral common carotid artery occlusion (BCCAO) surgery and administered ligustrazine intragastrically for 6 weeks. At the end of the experiments, the hippocampal biomarkers brain\u2010derived neurotrophic factor (BDNF), monocyte chemotactic protein 1 (MCP\u20101), and homocysteine (Hcy) were examined. In experiments <jats:italic>in vitro<\/jats:italic>, OGD PC12 cells were treated with ligustrazine for 0.5, 1, 3, 6, 12, or 24 h. The cell\u2010released biomarkers BDNF, MCP\u20101, and Hcy were examined. Microscopy, acridine orange\u2013ethidium bromide (AO\/EB) staining, and flow cytometry assays were performed to investigate apoptosis. Cleaved caspase\u20103, Bcl\u20102 associated X protein (Bax), and B cell lymphoma 2 (Bcl\u20102) expression was examined using Western blot assays. The results showed that biomarkers, including MCP\u20101 and Hcy, were significantly increased in both the <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> models, while the BDNF level was significantly decreased compared with the sham or vehicle models. Microscopy, AO\/EB staining, and flow cytometry analysis showed that severe cell damage occurred in OGD PC12 cells, and apoptosis played a major role in this environment. Further Western blot studies showed that the apoptosis\u2010related Bax\/Bcl\u20102 protein ratio and cleaved caspase\u20103 were significantly increased in the experiment. However, ligustrazine profoundly suppressed the imbalance of these biomarkers, reduced cell damage, decreased the Bax\/Bcl\u20102, and downregulated cleaved caspase\u20103. Pro\u2010 and anti\u2010apoptotic biomarkers of multiple pathways including BDNF, MCP\u20101, and Hcy played a joint role in triggering the activation of the mitochondria\u2010related Bax\/Bcl\u20102 and caspase\u20103 apoptosis pathway in VD. Ligustrazine attenuated VD by comprehensively regulating BDNF, MCP\u20101, and Hcy and inactivating the Bax\/Bcl\u20102 and caspase\u20103 apoptosis pathway. Our data provide novel insight into ligustrazine, which is a promising neuroprotective agent for VD disease treatment strategies. \u00a9 IUBMB Life, 70(1):60\u201370, 2018<\/jats:p>","DOI":"10.1002\/iub.1704","type":"journal-article","created":{"date-parts":[[2017,12,16]],"date-time":"2017-12-16T22:49:14Z","timestamp":1513464554000},"page":"60-70","source":"Crossref","is-referenced-by-count":118,"title":["Ligustrazine suppresses neuron apoptosis via the Bax\/Bcl\u20102 and caspase\u20103 pathway in PC12 cells and in rats with vascular dementia"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8006-5581","authenticated-orcid":false,"given":"Tengfei","family":"Zhao","sequence":"first","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxue","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanjing University of Chinese Medicine Nanjing China"},{"name":"Key Laboratory of Efficacy and Safety Evaluation of Traditional Chinese Medicine in Jiangsu Province Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanjing University of Chinese Medicine Nanjing China"},{"name":"Key Laboratory of Efficacy and Safety Evaluation of Traditional Chinese Medicine in Jiangsu Province Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoquan","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2015.2365"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.156991"},{"key":"e_1_2_8_4_1","first-page":"747","article-title":"Observation on curative effect of acute ischemic cerebrovascular disease treated with different dosage of ligustrazine","volume":"20","author":"Cai Y.","year":"2000","journal-title":"Zhongguo Zhong Xi Yi Jie He Za Zhi"},{"key":"e_1_2_8_5_1","first-page":"771","article-title":"Effect of ligustrazine on nNOS expression and neuranagenesis in adult rats after cerebral ischemia\u2010reperfusion injury","volume":"27","author":"Qi C. 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