{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:13:39Z","timestamp":1788912819994,"version":"build-2803163510"},"reference-count":75,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,9]],"date-time":"2020-08-09T00:00:00Z","timestamp":1596931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A2C2003750"],"award-info":[{"award-number":["NRF-2019R1A2C2003750"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A2C1005791"],"award-info":[{"award-number":["NRF-2019R1A2C1005791"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017M37A1025369"],"award-info":[{"award-number":["2017M37A1025369"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Type 1 diabetes mellitus is known to be linked to the impairment of blood\u2013brain barrier (BBB) integrity following neuronal cell death. Here, we investigated whether GS-KG9 and GS-E3D, bioactive ginseng extracts from Korean ginseng (Panax ginseng Meyer), inhibit BBB disruption following neuronal death in the hippocampus in streptozotocin-induced diabetic rats showing type 1-like diabetes mellitus. GS-KG9 and GS-E3D (50, 150, or 300 mg\/kg, twice a day for 4 weeks) administered orally showed antihyperglycemic activity in a dose-dependent manner and significantly attenuated the increase in BBB permeability and loss of tight junction proteins. GS-KG9 and GS-E3D also inhibited the expression and activation of matrix metalloproteinase-9 and the infiltration of macrophages into the brain parenchyma, especially into the hippocampal region. In addition, microglia and astrocyte activation in the hippocampus and the expression of proinflammatory mediators such as tnf-\u03b1, Il-1\u03b2, IL-6, cox-2, and inos were markedly alleviated in GS-KG9 and GS-E3D-treated group. Furthermore, apoptotic cell death of hippocampal neurons, especially in CA1 region, was significantly reduced in GS-KG9 and GS-E3D-treated groups as compared to vehicle control. These results suggest that GS-KG9 and GS-E3D effectively prevent apoptotic cell death of hippocampal neurons by inhibiting BBB disruption and may be a potential therapy for the treatment of diabetic patients.<\/jats:p>","DOI":"10.3390\/nu12082383","type":"journal-article","created":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T05:07:23Z","timestamp":1597036043000},"page":"2383","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Ginseng Extracts, GS-KG9 and GS-E3D, Prevent Blood\u2013Brain Barrier Disruption and Thereby Inhibit Apoptotic Cell Death of Hippocampal Neurons in Streptozotocin-Induced Diabetic Rats"],"prefix":"10.3390","volume":"12","author":[{"given":"Jee","family":"Lee","sequence":"first","affiliation":[{"name":"Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Park","sequence":"additional","affiliation":[{"name":"Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Biomedical Science, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae","family":"Choi","sequence":"additional","affiliation":[{"name":"Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Pyo","sequence":"additional","affiliation":[{"name":"International Ginseng and Herb Research Institute, Geumsan 32724, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae","family":"Yune","sequence":"additional","affiliation":[{"name":"Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Biomedical Science, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea"},{"name":"KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1111\/j.1464-5491.2004.01314.x","article-title":"Diurnal blood glucose profiles in women with gestational diabetes with or without hypertension","volume":"21","author":"Leinonen","year":"2004","journal-title":"Diabet. 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