{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:41:42Z","timestamp":1789015302772,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,9]],"date-time":"2025-03-09T00:00:00Z","timestamp":1741478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FDCT grant from the Macao Science and Technology Development Fund","award":["0124\/2022\/A"],"award-info":[{"award-number":["0124\/2022\/A"]}]},{"name":"FDCT grant from the Macao Science and Technology Development Fund","award":["002\/2023\/ALC"],"award-info":[{"award-number":["002\/2023\/ALC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Middle-aged and elderly individuals may experience detrimental health effects due to ischemic stroke (IS). The inflammatory response triggered during IS exacerbates neuronal damage, becoming a barrier to effective IS treatment and leading to poor patient prognosis. Nevertheless, the specific role of microglia in the inflammatory response triggered by IS remains mostly unclear. The primary target of this investigation is to study the neuroinflammatory impact of lycorine (LYC) during the IS process. Our objective is to evaluate whether LYC deploys its anti-inflammatory effect with modulation of the NF-\u03baB signaling pathway, thereby reducing IS symptoms. Methods: In this research, BV-2 cells were pre-treated with LYC for 24 h before LPS was added to induce inflammation. Results: It has been discovered that LYC suppresses BV-2 cell polarization and reduces the levels of inflammatory cytokines (IL-1\u03b2, IL-6, TNF-\u03b1), showing its potential anti-inflammatory effects in vitro. Furthermore, I\u03baB\u03b1 and p65 play crucial roles in regulating the inflammatory response within the NF-\u03baB signaling pathway. Mechanistic exploration indicates that LYC can activate the expression of I\u03baB\u03b1 in LPS-induced BV-2 cells. I\u03baB\u03b1 inhibits NF-\u03baB by binding to its p65 subunit, sequestering it in the cytoplasm and preventing its translocation to the nucleus, thereby inhibiting inflammation. Additionally, p65 is a key transcription factor for pro-inflammatory genes, and its downregulation leads to decreased transcriptional activity of these genes. The combined effect of increased I\u03baB\u03b1 and decreased p65 results in significantly reduced NF-\u03baB activity, thereby alleviating the inflammatory response. Meanwhile, in vivo studies indicate that LYC pre-treatment significantly reduces the infarct size caused by middle cerebral artery occlusion (MCAO) in rats. The assessment of cerebral infarction volume, neurological scores, brain edema rate and inflammation levels in MCAO rats pre-treated with LYC indicates positive therapeutic effects. Conclusions: In summary, our research indicates that LYC pre-treatment has significant anti-inflammatory effects by attenuating inflammation levels through NF-\u03baB inhibition, which contributes to potential therapeutic benefits in ischemic stroke (IS) and may improve disease prognosis. LYC may serve as an adjunctive clinical pre-treatment for IS, which has to be confirmed by clinical trials in the future.<\/jats:p>","DOI":"10.3390\/brainsci15030290","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T06:59:59Z","timestamp":1741589999000},"page":"290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lycorine Pre-Treatment Alleviates Microglia Inflammation After Cerebral Ischemia by Inhibiting NF-\u03baB Phosphorylation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5133-9472","authenticated-orcid":false,"given":"Wuyan","family":"Zheng","sequence":"first","affiliation":[{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Li","sequence":"additional","affiliation":[{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Qin","sequence":"additional","affiliation":[{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau SAR, China"},{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Wang","sequence":"additional","affiliation":[{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau SAR, China"},{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty Yuen Kwan","family":"Law","sequence":"additional","affiliation":[{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent Kam Wai","family":"Wong","sequence":"additional","affiliation":[{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41572-019-0118-8","article-title":"Ischaemic stroke","volume":"5","author":"Campbell","year":"2019","journal-title":"Nat. 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