Gastrodin improves neuroinflammation-induced cognitive dysfunction in rats by regulating NLRP3 inflammasome.
Gastrodin improves neuroinflammation-induced cognitive dysfunction in rats by regulating NLRP3 inflammasome.
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DOI：
10.1186/s12871-022-01915-y
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发表时间：
2022-12-01
影响因子：
2.2
通讯作者：
Zhu, Zhaoqiong
中科院分区：
文献类型：
--
作者：
Zheng, Xue;Gong, Taowu;Tang, Chunchun;Zhong, Yuanping;Shi, Lu;Fang, Xu;Chen, Dongqin;Zhu, Zhaoqiong
关键词：
神经炎症是神经退行性疾病引起认知功能障碍的主要病理机制，目前尚无有效的预防和治疗措施。我们通过网络药理学和分子对接预测了天麻素对神经炎症作用的关键靶点。利用预测的靶点研究天麻素对脂多糖诱导的大鼠神经炎症性认知功能障碍的影响及其机制。3月龄雄性大鼠腹腔注射脂多糖3d、7 d和14 d。天麻素改善神经炎症大鼠的学习记忆能力。脂多糖可增加大鼠海马TNF-α、IL-1β和IL-6等促炎性细胞因子的水平，天麻素可逆转脂多糖的上述作用。天麻素还抑制了小胶质细胞的活化。我们的研究结果表明，天麻素通过影响TLR 4-NF-kB-NLRP 3通路，在神经炎症大鼠中发挥神经保护作用。因此，天麻素可能是一种潜在的治疗神经炎症性认知功能障碍的药物。在线版本包含补充材料，可通过10.1186/s12871-022-01915-y获得。
Neuroinflammation is the main pathological mechanism of cognitive dysfunction caused by neurodegenerative diseases, and effective preventive and therapeutic measures are not available. We predicted the key targets of gastrodin’s effects upon neuroinflammation through Network Pharmacology and molecular docking. Then the predicted targets were used to study how gastrodin affected cognitive dysfunction triggered by lipopolysaccharide-induced neuroinflammation in rats and its mechanisms. Three-month-old male rats were intraperitoneally injected with lipopolysaccharide for 3 days (d), 7 d and 14 d respectively. Gastrodin improved learning and memory ability of rats with neuroinflammation. Lipopolysaccharide enhanced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6, in rat hippocampus, which could be reversed by gastrodin. Gastrodin also inhibited the activation of microglia. Our findings suggested that gastrodin exerted neuroprotective effects in rats with neuroinflammation by impacting the TLR4-NF-kB-NLRP3 pathway. Therefore, gastrodin may be a potential therapeutic agent for neuroinflammation-induced cognitive dysfunction. The online version contains supplementary material available at 10.1186/s12871-022-01915-y.
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