Zheng Wuyan, Wu Wanyu, Li Yuhan, Qin Bo, Wang Yuping, Zeng Yunhan, Law Betty Yuen Kwan, Wong Vincent Kam Wai
Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau SAR, China.
The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China.
Brain Sci. 2025 Mar 9;15(3):290. doi: 10.3390/brainsci15030290.
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-κB signaling pathway, thereby reducing IS symptoms.
In this research, BV-2 cells were pre-treated with LYC for 24 h before LPS was added to induce inflammation.
It has been discovered that LYC suppresses BV-2 cell polarization and reduces the levels of inflammatory cytokines (IL-1β, IL-6, TNF-α), showing its potential anti-inflammatory effects in vitro. Furthermore, IκBα and p65 play crucial roles in regulating the inflammatory response within the NF-κB signaling pathway. Mechanistic exploration indicates that LYC can activate the expression of IκBα in LPS-induced BV-2 cells. IκBα inhibits NF-κB 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 IκBα and decreased p65 results in significantly reduced NF-κB 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.
In summary, our research indicates that LYC pre-treatment has significant anti-inflammatory effects by attenuating inflammation levels through NF-κB 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.
中老年个体可能因缺血性中风（IS）而出现健康损害。IS期间引发的炎症反应会加剧神经元损伤，成为IS有效治疗的障碍，并导致患者预后不良。然而，小胶质细胞在IS引发的炎症反应中的具体作用仍大多不明。本研究的主要目的是探讨石蒜碱（LYC）在IS过程中的神经炎症影响。我们的目标是评估LYC是否通过调节核因子κB（NF-κB）信号通路发挥其抗炎作用，从而减轻IS症状。
在本研究中，在添加脂多糖（LPS）诱导炎症之前，先用LYC对BV-2细胞进行24小时预处理。
已发现LYC可抑制BV-2细胞极化，并降低炎症细胞因子（白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α）水平，显示出其在体外的潜在抗炎作用。此外，IκBα和p65在调节NF-κB信号通路中的炎症反应中起关键作用。机制探索表明，LYC可激活LPS诱导的BV-2细胞中IκBα的表达。IκBα通过与其p65亚基结合来抑制NF-κB，将其隔离在细胞质中并阻止其转运至细胞核，从而抑制炎症。此外，p65是促炎基因的关键转录因子，其下调导致这些基因的转录活性降低。IκBα增加和p65减少的联合作用导致NF-κB活性显著降低，从而减轻炎症反应。同时，体内研究表明，LYC预处理可显著减小大鼠大脑中动脉闭塞（MCAO）所致的梗死面积。对LYC预处理的MCAO大鼠的脑梗死体积、神经功能评分、脑水肿率和炎症水平的评估显示出积极的治疗效果。
总之，我们的研究表明，LYC预处理通过抑制NF-κB减轻炎症水平，具有显著的抗炎作用，这有助于在缺血性中风（IS）中发挥潜在治疗益处，并可能改善疾病预后。LYC可能作为IS的辅助临床预处理方法，这有待未来的临床试验证实。
