{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:48:00Z","timestamp":1787237280369,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,2]],"date-time":"2019-01-02T00:00:00Z","timestamp":1546387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Natural sources are very promising materials for the discovery of novel bioactive compounds with diverse pharmacological effects. In recent years, many researchers have focused on natural sources as a means to prevent neuronal cell death in neuropathological conditions. This study focused on identifying neuroprotective compounds and their underlying molecular mechanisms. Procyanidin C1 (PC-1) was isolated from grape seeds and assessed for biological effects against glutamate-induced HT22 cell death. The results showed that PC-1 strongly prevented glutamate-induced HT22 cell death. Moreover, PC-1 was also found to prevent glutamate-induced chromatin condensation and reduce the number of annexin V-positive cells indicating apoptotic cell death. Procyanidin C1 possessed a strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and inhibited glutamate-induced accumulation of intracellular reactive oxygen species and protein carbonylation. Additionally, PC-1 mediated nuclear translocation of nuclear factor erythroid-derived 2-related factor 2 and increased the expression levels of heme oxygenase (HO-1). Inhibition of HO-1 by tin protoporphyrin, a synthetic inhibitor, reduced the protective effect of PC-1. Furthermore, PC-1 also blocked glutamate-induced phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1\/2 and p38, but not JNK. This study is the first experimental report to demonstrate the neuroprotective effects of PC-1 against glutamate-induced cytotoxicity in HT22 cells. Therefore, our results suggest that PC-1, as a potent bioactive compound of grape seeds, can prevent neuronal cell death in neuropathological conditions.<\/jats:p>","DOI":"10.3390\/ijms20010142","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T03:36:30Z","timestamp":1546486590000},"page":"142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Procyanidin C1 Activates the Nrf2\/HO-1 Signaling Pathway to Prevent Glutamate-Induced Apoptotic HT22 Cell Death"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5141-5546","authenticated-orcid":false,"given":"Ji Hoon","family":"Song","sequence":"first","affiliation":[{"name":"College of Korean Medicine, Gachon University, Seongnam 13120, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8353-3619","authenticated-orcid":false,"given":"Hae-Jeung","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Bio-Nano Technology, Department of Food and Nutrition, Gachon University, Seongnam 13120, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Sung","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Gachon University, Seongnam 13120, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1002\/ana.410320706","article-title":"Free radical damage to protein and DNA: Mechanisms involved and relevant observations on brain undergoing oxidative stress","volume":"32","author":"Floyd","year":"1992","journal-title":"Ann. 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