{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:06:27Z","timestamp":1760058387901,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"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>This study aimed to investigate the inhibitory effect of the chloroform fraction (CF) from Vitis vinifera root extract on LPS-induced neuroinflammation in BV-2 microglia cells and a C57\/BL6J mouse model. CF significantly suppressed LPS-induced proinflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-\u03b1 (TNF-\u03b1), and interleukin-6 (IL-6) in BV-2 microglia cells. Mechanistically, CF inhibited LPS-induced activation of nuclear factor-\u03baB (NF-\u03baB) by blocking the p65 subunit and preventing the phosphorylation of NF-kappa-B inhibitor \u03b1 (I\u03baB\u03b1), while its effect was independent of the mitogen-activated protein kinase (MAPK) pathway. Furthermore, CF modulated the TRIF signaling pathway by regulating TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3), which contributed to the suppression of inflammatory mediators in BV-2 microglia cells. In vivo, we evaluated the neuroprotective effects of CF against cognitive dysfunction and inflammatory responses in an LPS-induced mouse model. Our behavioral assessments, including the Morris water maze and Y-maze tests, demonstrated that CF alleviated LPS-induced spatial learning impairment and cognitive decline. Additionally, CF significantly reduced the levels of inflammatory cytokines in serum and inflammatory mediators proteins expression in whole brain in LPS-injected mice, suggesting a direct link between reduced inflammatory responses and improved cognitive function. These findings suggest that CF from V. vinifera root extract may serve as a potential therapeutic strategy for neurodegenerative diseases mediated by microglial activation, such as Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms26073126","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T06:06:35Z","timestamp":1743141995000},"page":"3126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Chloroform Fraction Derived from Vitis vinifera Root Ethanol Extract Attenuates Lipopolysaccharide-Induced Inflammatory Responses and Cognitive Dysfunction in BV-2 Microglia Cells and C57BL\/6J Mouse Model"],"prefix":"10.3390","volume":"26","author":[{"given":"Yon-Suk","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Research Institute of Inflammatory Disease (RID), College of Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Bong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Applied Life Sciences, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin-Il","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Applied Life Sciences, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo-Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Biocenter, Gyeonggido Business and Science Accelerator, Gwanggyo-ro 147, Yeongtong-gu, Suwon 16229, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-1524","authenticated-orcid":false,"given":"Dong-Kug","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Research Institute of Inflammatory Disease (RID), College of Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea"},{"name":"Department of Applied Life Sciences, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yin, G., Pan, C., Liu, H., Dong, C., Chang, X., Zhou, W., Wang, S., and Du, Z. 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