{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:40:32Z","timestamp":1790822432241,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:00:00Z","timestamp":1760227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013129","name":"Ministry of Small and Medium-sized Enterprises (SMEs) and Startups","doi-asserted-by":"publisher","award":["S3400191"],"award-info":[{"award-number":["S3400191"]}],"id":[{"id":"10.13039\/501100013129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In our previous study, we demonstrated that a standardized ethanol extract of Perilla frutescens var. acuta (PE) alleviates memory deficits in an Alzheimer\u2019s disease mouse model by inhibiting amyloid \u03b2 (A\u03b2) aggregation and promoting its disaggregation. However, the extent to which PE exerts additional cognitive benefits independent of A\u03b2 pathology remained unclear. Here, we aimed to evaluate the effects of PE on synaptic plasticity and learning and memory functions. Male ICR mice were used, and cognitive impairment was induced by scopolamine administration. PE was orally administered at doses determined from previous studies, and cognitive performance was assessed using the passive avoidance, Y-maze, and Morris water maze tests. In parallel, hippocampal slices were employed to examine the effects of PE on synaptic plasticity. PE (100 and 300 \u03bcg\/mL) significantly enhanced long-term potentiation (LTP) in a concentration-dependent manner without altering basal synaptic transmission. This facilitation of LTP was blocked by scopolamine (1 \u03bcM), a muscarinic acetylcholine receptor (mAChR) antagonist, and IEM-1460 (50 \u03bcM), a calcium-permeable \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (CP-AMPAR) inhibitor, indicating the involvement of mAChR and CP-AMPAR pathways. In vivo, PE (100, 250, and 500 mg\/kg) treatment improved memory performance across all behavioral tasks and upregulated hippocampal synaptic proteins including GluN2B, PSD-95, and CaMKII. Collectively, these results demonstrate that PE ameliorates scopolamine (1 mg\/kg)-induced cognitive impairment by enhancing synaptic plasticity, likely through modulation of mAChR, CP-AMPAR, and NMDA receptor signaling. These findings highlight the therapeutic potential of PE for memory deficits associated with cholinergic dysfunction.<\/jats:p>","DOI":"10.3390\/ijms26209925","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T16:13:03Z","timestamp":1760717583000},"page":"9925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synaptic Plasticity-Enhancing and Cognitive-Improving Effects of Standardized Ethanol Extract of Perilla frutescens var. acuta in a Scopolamine-Induced Mouse Model"],"prefix":"10.3390","volume":"26","author":[{"given":"Jihye","family":"Lee","sequence":"first","affiliation":[{"name":"Industry-Academic Cooperation Foundation, Daegu Haany University, 1 Hanuidae-ro, Gyeongsan 38610, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunhong","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeonngsan 38541, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunji","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Advanced Translational Medicine, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somin","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Advanced Translational Medicine, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Jung","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Bio Health Science, College of Natural Science, Changwon National University, Changwon 51140, Gyeongsangnam-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon-Ho","family":"Hwang","sequence":"additional","affiliation":[{"name":"Borambio Co., Ltd., 119, Dandae-ro, Dongnam-gu, Cheonan 31116, Chungcheongnam-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun Hee","family":"Cho","sequence":"additional","affiliation":[{"name":"Borambio Co., Ltd., 119, Dandae-ro, Dongnam-gu, Cheonan 31116, Chungcheongnam-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haram","family":"Kong","sequence":"additional","affiliation":[{"name":"Borambio Co., Ltd., 119, Dandae-ro, Dongnam-gu, Cheonan 31116, Chungcheongnam-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Houn","family":"Park","sequence":"additional","affiliation":[{"name":"Borambio Co., Ltd., 119, Dandae-ro, Dongnam-gu, Cheonan 31116, Chungcheongnam-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Borambio Co., Ltd., 119, Dandae-ro, Dongnam-gu, Cheonan 31116, Chungcheongnam-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0540-4739","authenticated-orcid":false,"given":"Dong Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Konkuk University, 268 Chungwon-daero, Chungju-si 27478, Chungcheongbuk-do, Republic of Korea"},{"name":"Research Institute of Medical Science, Konkuk University School of Medicine, 268 Chungwon-daero, Chungju-si 27478, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Wook","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Cosmetics, College of K-Bio Health, Daegu Haany University, 285-10, Eobongji-gil, Gyeongsan 38578, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111905","DOI":"10.1016\/j.paid.2022.111905","article-title":"Early-life home environment and child cognitive function: A meta-analysis","volume":"200","author":"Han","year":"2023","journal-title":"Personal. 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