Sinomenine regulates the cholinergic anti-inflammatory pathway to inhibit TLR4/NF-κB pathway and protect the homeostasis in brain and gut in scopolamine-induced Alzheimer's disease mice
Sinomenine regulates the cholinergic anti-inflammatory pathway to inhibit TLR4/NF-κB pathway and protect the homeostasis in brain and gut in scopolamine-induced Alzheimer's disease mice
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DOI：
10.1016/j.biopha.2024.116190
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发表时间：
2024-01-26
影响因子：
7.5
通讯作者：
Dong，Yan
中科院分区：
文献类型：
--
作者：
Ni，Haojie;Liu，Muqiu;Dong，Yan
青藤碱（Sinomenine，SIN）是从中药青风藤（Sinomenium acutum）中提取的生物碱，具有抗炎、免疫调节、镇痛、镇静等作用，在我国已成为治疗类风湿关节炎的临床药物。本课题组前期研究表明SIN通过调节胆碱能抗炎通路（CAP）的关键受体β 7 nAChR来抑制炎症反应，而CAP在调节外周和中枢神经系统炎症反应中起重要作用。越来越多的证据支持胆碱能调节异常和炎症反应在AD的发病机制中起关键作用。本研究首次以东莨菪碱诱导的AD模型小鼠为研究对象，分析了SIN通过调节CAP和脑、肠内稳态对AD的干预作用。行为测试用于评估认知表现。通过多种技术评价小鼠脑和肠组织的神经元损失、胆碱能功能、炎症反应、生物屏障功能，并使用16 SrRNA测序检测肠道菌群。结果表明，SIN对SCOP所致小鼠认知功能下降、胆碱能系统失调、外周和中枢炎症、生物屏障损伤及肠道植物群紊乱均有明显的抑制作用。更重要的是，SIN能有效调节CAP，抑制TLR 4/NF-κB的活化，保护脑和肠道内环境的稳定，从而减轻认知障碍。
Sinomenine (SIN), an alkaloid extracted from the Chinese herbal medicineSinomenium acutum, has great potential in anti-inflammatory, immune regulation, analgesic and sedative, and is already a clinical drug for the treatment of rheumatoid arthritis in China. Our previous studies show SIN inhibits inflammation by regulating ɑ7nAChR, a key receptor of cholinergic anti-inflammatory pathway (CAP), which plays an important role in regulating peripheral and central nervous system inflammation. Growing evidence supports the cholinergic dysregulation and inflammatory responses play the key role in the pathogenesis of AD. The intervention effects of SIN on AD by regulating CAP and homeostasis in brain and gut were analyzed for the first time in the present study using scopolamine-induced AD model mice. Behavioral tests were used to assess the cognitive performance. The neurons loss, cholinergic function, inflammation responses, biological barrier function in the mouse brain and intestinal tissues were evaluated through a variety of techniques, and the gut microbiota was detected using 16SrRNA sequencing. The results showed that SIN significantly inhibited the cognitive decline, dysregulation of cholinergic system, peripheral and central inflammation, biological barrier damage as well as intestinal flora disturbance caused by SCOP in mice. More importantly, SIN effectively regulated CAP to suppress the activation of TLR4/NF-κB and protect the homeostasis in brain and gut to alleviate cognitive impairment.