{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T21:30:28Z","timestamp":1782250228616,"version":"3.54.5"},"reference-count":58,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003711","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 110-2320-B-030-009"],"award-info":[{"award-number":["MOST 110-2320-B-030-009"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chi-Mei Medical Center","award":["107-CM-FJU-03"],"award-info":[{"award-number":["107-CM-FJU-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Rosmarinic acid, a major component of rosemary, is a polyphenolic compound with potential neuroprotective effects. Asreducing the synaptic release of glutamate is crucial to achieving neuroprotectant\u2019s pharmacotherapeutic effects, the effect of rosmarinic acid on glutamate release was investigated in rat cerebrocortical nerve terminals (synaptosomes). Rosmarinic acid depressed the 4-aminopyridine (4-AP)-induced glutamate release in a concentration-dependent manner. The removal of extracellular calcium and the blockade of vesicular transporters prevented the inhibition of glutamate release by rosmarinic acid. Rosmarinic acid reduced 4-AP-induced intrasynaptosomal Ca2+ elevation. The inhibition of N-, P\/Q-type Ca2+ channels and the calcium\/calmodulin-dependent kinase II (CaMKII) prevented rosmarinic acid from having effects on glutamate release. Rosmarinic acid also reduced the 4-AP-induced activation of CaMKII and the subsequent phosphorylation of synapsin I, the main presynaptic target of CaMKII. In addition, immunocytochemistry confirmed the presence of GABAA receptors. GABAA receptor agonist and antagonist blocked the inhibitory effect of rosmarinic acid on 4-AP-evoked glutamate release. Docking data also revealed that rosmarinic acid formed a hydrogen bond with the amino acid residues of GABAA receptor. These results suggested that rosmarinic acid activates GABAA receptors in cerebrocortical synaptosomes to decrease Ca2+ influx and CaMKII\/synapsin I pathway to inhibit the evoked glutamate release.<\/jats:p>","DOI":"10.3390\/biom11071029","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T02:52:34Z","timestamp":1626317554000},"page":"1029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Rosmarinic Acid, a Bioactive Phenolic Compound, Inhibits Glutamate Release from Rat Cerebrocortical Synaptosomes through GABAA Receptor Activation"],"prefix":"10.3390","volume":"11","author":[{"given":"Che-Chuan","family":"Wang","sequence":"first","affiliation":[{"name":"Chi Mei Medical Center, Department of Neurosurgery, Tainan 71004, Taiwan"},{"name":"Biotechnology, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8882-4711","authenticated-orcid":false,"given":"Pei-Wen","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan"},{"name":"Graduate Institute of Natural Products, School of Traditional Chinese Medicine, and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33303, Taiwan"},{"name":"Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 33303, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinn-Rung","family":"Kuo","sequence":"additional","affiliation":[{"name":"Chi Mei Medical Center, Department of Neurosurgery, Tainan 71004, Taiwan"},{"name":"Biotechnology, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4675-0259","authenticated-orcid":false,"given":"Su-Jane","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan"},{"name":"School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s11033-010-0128-9","article-title":"Glutamate receptors and signal transduction in learning and memory","volume":"38","author":"Peng","year":"2011","journal-title":"Mol. 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