{"title":"芦荟素通过抑制 TLR4 介导的神经炎症,改善新生小鼠缺氧缺血性脑损伤。","authors":"Liping Chen, Siqing Xiong, Xiaofan Zhou, Qiang Fu","doi":"10.1002/iid3.1320","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>At present, neonatal hypoxic-ischemic encephalopathy (HIE), especially moderate to severe HIE, is a challenging disease for neonatologists to treat, and new alternative/complementary treatments are urgently needed. The neuroinflammatory cascade triggered by hypoxia-ischemia (HI) insult is one of the core pathological mechanisms of HIE. Early inhibition of neuroinflammation provides long-term neuroprotection. Plant-derived monomers have impressive anti-inflammatory effects. Aloesin (ALO) has been shown to have significant anti-inflammatory and antioxidant effects in diseases such as ulcerative colitis, but its role in HIE is unclear. To this end, we conducted a series of experiments to explore the potential mechanism of ALO in preventing and treating brain damage caused by HI insult.</p>\n </section>\n \n <section>\n \n <h3> Materials and Methods</h3>\n \n <p>Hypoxic-ischemic brain damage (HIBD) was induced in 7-day-old Institute of Cancer Research (ICR) mice, which were then treated with 20 mg/kg ALO. The neuroprotective effects of ALO on HIBD and the underlying mechanism were evaluated through neurobehavioral testing, infarct size measurement, apoptosis detection, protein and messenger RNA level determination, immunofluorescence, and molecular docking.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>ALO alleviated the long-term neurobehavioral deficits caused by HI insult; reduced the extent of cerebral infarction; inhibited cell apoptosis; decreased the levels of the inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor-α; activated microglia and astrocytes; and downregulated the protein expression of members in the TLR4 signaling pathway. In addition, molecular docking showed that ALO can bind stably to TLR4.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>ALO ameliorated HIBD in neonatal mice by inhibiting the neuroinflammatory response mediated by TLR4 signaling.</p>\n </section>\n </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.1320","citationCount":"0","resultStr":"{\"title\":\"Aloesin ameliorates hypoxic-ischemic brain damage in neonatal mice by suppressing TLR4-mediated neuroinflammation\",\"authors\":\"Liping Chen, Siqing Xiong, Xiaofan Zhou, Qiang Fu\",\"doi\":\"10.1002/iid3.1320\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>At present, neonatal hypoxic-ischemic encephalopathy (HIE), especially moderate to severe HIE, is a challenging disease for neonatologists to treat, and new alternative/complementary treatments are urgently needed. The neuroinflammatory cascade triggered by hypoxia-ischemia (HI) insult is one of the core pathological mechanisms of HIE. Early inhibition of neuroinflammation provides long-term neuroprotection. Plant-derived monomers have impressive anti-inflammatory effects. Aloesin (ALO) has been shown to have significant anti-inflammatory and antioxidant effects in diseases such as ulcerative colitis, but its role in HIE is unclear. To this end, we conducted a series of experiments to explore the potential mechanism of ALO in preventing and treating brain damage caused by HI insult.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Materials and Methods</h3>\\n \\n <p>Hypoxic-ischemic brain damage (HIBD) was induced in 7-day-old Institute of Cancer Research (ICR) mice, which were then treated with 20 mg/kg ALO. The neuroprotective effects of ALO on HIBD and the underlying mechanism were evaluated through neurobehavioral testing, infarct size measurement, apoptosis detection, protein and messenger RNA level determination, immunofluorescence, and molecular docking.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>ALO alleviated the long-term neurobehavioral deficits caused by HI insult; reduced the extent of cerebral infarction; inhibited cell apoptosis; decreased the levels of the inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor-α; activated microglia and astrocytes; and downregulated the protein expression of members in the TLR4 signaling pathway. In addition, molecular docking showed that ALO can bind stably to TLR4.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>ALO ameliorated HIBD in neonatal mice by inhibiting the neuroinflammatory response mediated by TLR4 signaling.</p>\\n </section>\\n </div>\",\"PeriodicalId\":13289,\"journal\":{\"name\":\"Immunity, Inflammation and Disease\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-06-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.1320\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunity, Inflammation and Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/iid3.1320\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunity, Inflammation and Disease","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/iid3.1320","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:目前,新生儿缺氧缺血性脑病(HIE),尤其是中重度缺氧缺血性脑病,是新生儿科医生面临的一个治疗难题,迫切需要新的替代/辅助治疗方法。缺氧缺血(HI)损伤引发的神经炎症级联反应是 HIE 的核心病理机制之一。早期抑制神经炎症可提供长期的神经保护。植物提取的单体具有令人印象深刻的抗炎作用。芦荟素(ALO)已被证明在溃疡性结肠炎等疾病中具有显著的抗炎和抗氧化作用,但其在 HIE 中的作用尚不清楚。为此,我们进行了一系列实验,以探索 ALO 预防和治疗 HI 损伤引起的脑损伤的潜在机制。通过神经行为测试、脑梗塞大小测量、细胞凋亡检测、蛋白质和信使RNA水平测定、免疫荧光和分子对接等方法评估了ALO对HIBD的神经保护作用及其内在机制:结果:ALO减轻了HI损伤引起的长期神经行为障碍,缩小了脑梗塞范围,抑制了细胞凋亡,降低了炎症因子白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α的水平,激活了小胶质细胞和星形胶质细胞,并下调了TLR4信号通路成员的蛋白表达。此外,分子对接显示 ALO 可与 TLR4 稳定结合:结论:ALO能抑制TLR4信号传导介导的神经炎症反应,从而改善新生小鼠的HIBD。
Aloesin ameliorates hypoxic-ischemic brain damage in neonatal mice by suppressing TLR4-mediated neuroinflammation
Background
At present, neonatal hypoxic-ischemic encephalopathy (HIE), especially moderate to severe HIE, is a challenging disease for neonatologists to treat, and new alternative/complementary treatments are urgently needed. The neuroinflammatory cascade triggered by hypoxia-ischemia (HI) insult is one of the core pathological mechanisms of HIE. Early inhibition of neuroinflammation provides long-term neuroprotection. Plant-derived monomers have impressive anti-inflammatory effects. Aloesin (ALO) has been shown to have significant anti-inflammatory and antioxidant effects in diseases such as ulcerative colitis, but its role in HIE is unclear. To this end, we conducted a series of experiments to explore the potential mechanism of ALO in preventing and treating brain damage caused by HI insult.
Materials and Methods
Hypoxic-ischemic brain damage (HIBD) was induced in 7-day-old Institute of Cancer Research (ICR) mice, which were then treated with 20 mg/kg ALO. The neuroprotective effects of ALO on HIBD and the underlying mechanism were evaluated through neurobehavioral testing, infarct size measurement, apoptosis detection, protein and messenger RNA level determination, immunofluorescence, and molecular docking.
Results
ALO alleviated the long-term neurobehavioral deficits caused by HI insult; reduced the extent of cerebral infarction; inhibited cell apoptosis; decreased the levels of the inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor-α; activated microglia and astrocytes; and downregulated the protein expression of members in the TLR4 signaling pathway. In addition, molecular docking showed that ALO can bind stably to TLR4.
Conclusion
ALO ameliorated HIBD in neonatal mice by inhibiting the neuroinflammatory response mediated by TLR4 signaling.
期刊介绍:
Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including:
• cellular and molecular immunology
• clinical immunology
• allergy
• immunochemistry
• immunogenetics
• immune signalling
• immune development
• imaging
• mathematical modelling
• autoimmunity
• transplantation immunology
• cancer immunology