{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:19:39Z","timestamp":1760242779905,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2016,6,24]],"date-time":"2016-06-24T00:00:00Z","timestamp":1466726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Science and Technology","award":["MOST 103-2320-B-030-001 MY3"],"award-info":[{"award-number":["MOST 103-2320-B-030-001 MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The glutamatergic system may be involved in the effects of neuroprotectant therapies. Echinacoside, a phenylethanoid glycoside extracted from the medicinal Chinese herb Herba Cistanche, has neuroprotective effects. This study investigated the effects of echinacoside on 4-aminopyridine-evoked glutamate release in rat cerebrocortical nerve terminals (synaptosomes). Echinacoside inhibited Ca2+-dependent, but not Ca2+-independent, 4-aminopyridine-evoked glutamate release in a concentration-dependent manner. Echinacoside also reduced the 4-aminopyridine-evoked increase in cytoplasmic free Ca2+ concentration but did not alter the synaptosomal membrane potential. The inhibitory effect of echinacoside on 4-aminopyridine-evoked glutamate release was prevented by \u03c9-conotoxin MVIIC, a wide-spectrum blocker of Cav2.2 (N-type) and Cav2.1 (P\/Q-type) channels, but was insensitive to the intracellular Ca2+ release-inhibitors dantrolene and 7-chloro-5-(2-chloropheny)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP37157). Furthermore, echinacoside decreased the 4-aminopyridine-induced phosphorylation of protein kinase C, and protein kinase C inhibitors abolished the effect of echinacoside on glutamate release. According to these results, we suggest that the inhibitory effect of echinacoside on evoked glutamate release is associated with reduced voltage-dependent Ca2+ entry and subsequent suppression of protein kinase C activity.<\/jats:p>","DOI":"10.3390\/ijms17071006","type":"journal-article","created":{"date-parts":[[2016,6,25]],"date-time":"2016-06-25T21:21:45Z","timestamp":1466889705000},"page":"1006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Echinacoside Inhibits Glutamate Release by Suppressing Voltage-Dependent Ca2+ Entry and Protein Kinase C in Rat Cerebrocortical Nerve Terminals"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2217-3231","authenticated-orcid":false,"given":"Cheng","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan"},{"name":"Department of Mechanical Engineering, Yuan Ze University, Taoyuan 32003, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1374-5189","authenticated-orcid":false,"given":"Tzu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan"},{"name":"Department of Mechanical Engineering, Yuan Ze University, Taoyuan 32003, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4675-0259","authenticated-orcid":false,"given":"Su","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei 24205, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,6,24]]},"reference":[{"key":"ref_1","first-page":"294","article-title":"Analysis of phenylethanoid glycosides of Herba cistanchis by RP-HPLC","volume":"32","author":"Tu","year":"1997","journal-title":"Acta Pharm. 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