{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:16:30Z","timestamp":1784740590646,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["111-2314-B-418-009-MY2"],"award-info":[{"award-number":["111-2314-B-418-009-MY2"]}]},{"name":"National Science and Technology Council","award":["112-2320-B-030-010-MY3"],"award-info":[{"award-number":["112-2320-B-030-010-MY3"]}]},{"name":"National Science and Technology Council","award":["111-FEMH-FJU-01"],"award-info":[{"award-number":["111-FEMH-FJU-01"]}]},{"name":"Far-Eastern Memorial Hospital","award":["111-2314-B-418-009-MY2"],"award-info":[{"award-number":["111-2314-B-418-009-MY2"]}]},{"name":"Far-Eastern Memorial Hospital","award":["112-2320-B-030-010-MY3"],"award-info":[{"award-number":["112-2320-B-030-010-MY3"]}]},{"name":"Far-Eastern Memorial Hospital","award":["111-FEMH-FJU-01"],"award-info":[{"award-number":["111-FEMH-FJU-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Excitotoxicity is a common pathological process in neurological diseases caused by excess glutamate. The purpose of this study was to evaluate the effect of gypenoside XVII (GP-17), a gypenoside monomer, on the glutamatergic system. In vitro, in rat cortical nerve terminals (synaptosomes), GP-17 dose-dependently decreased glutamate release with an IC50 value of 16 \u03bcM. The removal of extracellular Ca2+ or blockade of N-and P\/Q-type Ca2+ channels and protein kinase A (PKA) abolished the inhibitory effect of GP-17 on glutamate release from cortical synaptosomes. GP-17 also significantly reduced the phosphorylation of PKA, SNAP-25, and synapsin I in cortical synaptosomes. In an in vivo rat model of glutamate excitotoxicity induced by kainic acid (KA), GP-17 pretreatment significantly prevented seizures and rescued neuronal cell injury and glutamate elevation in the cortex. GP-17 pretreatment decreased the expression levels of sodium-coupled neutral amino acid transporter 1, glutamate synthesis enzyme glutaminase and vesicular glutamate transporter 1 but increased the expression level of glutamate metabolism enzyme glutamate dehydrogenase in the cortex of KA-treated rats. In addition, the KA-induced alterations in the N-methyl-D-aspartate receptor subunits GluN2A and GluN2B in the cortex were prevented by GP-17 pretreatment. GP-17 also prevented the KA-induced decrease in cerebral blood flow and arginase II expression. These results suggest that (i) GP-17, through the suppression of N- and P\/Q-type Ca2+ channels and consequent PKA-mediated SNAP-25 and synapsin I phosphorylation, reduces glutamate exocytosis from cortical synaptosomes; and (ii) GP-17 has a neuroprotective effect on KA-induced glutamate excitotoxicity in rats through regulating synaptic glutamate release and cerebral blood flow.<\/jats:p>","DOI":"10.3390\/biom14050589","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T06:44:31Z","timestamp":1715841871000},"page":"589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Gypenoside XVII Reduces Synaptic Glutamate Release and Protects against Excitotoxic Injury in Rats"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2217-3231","authenticated-orcid":false,"given":"Cheng-Wei","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei 22060, Taiwan"},{"name":"Department of Mechanical Engineering, Yuan Ze University, Taoyuan 32003, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1374-5189","authenticated-orcid":false,"given":"Tzu-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei 22060, Taiwan"},{"name":"Department of Mechanical Engineering, Yuan Ze University, Taoyuan 32003, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7597-7655","authenticated-orcid":false,"given":"Kuan-Ming","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Cardiovascular Center, Far-Eastern Memorial Hospital, New Taipei 22060, Taiwan"},{"name":"Department of Electrical Engineering, Yuan Ze University, Taoyuan 32003, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7742-9508","authenticated-orcid":false,"given":"Ming-Yi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Far-Eastern Memorial Hospital, New Taipei 22060, 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":"School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan"},{"name":"Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s00702-014-1180-8","article-title":"Glutamate as a neurotransmitter in the healthy brain","volume":"121","author":"Zhou","year":"2014","journal-title":"J. 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