Salidroside improves blood-brain barrier integrity and cognitive function in hypobaric hypoxia mice by inhibiting microglia activation through GSK3β.

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Xianxie Zhang, Huiting Zhang, Zuoxu Liu, Tianke Huang, Ru Yi, Zengchun Ma, Yue Gao
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Abstract

Salidroside, an active component found in Rhodiola rosea L., has emerged as a potential therapeutic agent for the prevention and treatment of hypoxic brain injury, while the precise target and mechanism of salidroside were remain unclear. The study utilized techniques such as network pharmacology, transcriptome sequencing to investigate the mechanism and target of salidroside in regulating blood-brain barrier (BBB) function to protect hypoxic brain injury in vivo. Utilized macromolecular docking and molecular biology techniques to explore the molecular mechanism of salidroside in alleviating brain injury induced by hypoxia in BV2 cell model. The results show that salidroside alleviated the learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia, reduced brain water content and attenuate the inflammatory response and oxidative stress, effectively reversed S100β in serum and promoted the repair of BBB. GSK3β is an important therapeutic target of salidroside in the treatment of hypoxic cognitive impairment, and salidroside can specifically bind GSK3β in the ATP binding pocket, inducing the phosphorylation of GSK3β, targeting downstream Nrf-2 to regulate microglia activity, promoting the accumulation of β-catenin, thereby inhibiting microglial activation, improving the BBB integrity injury and achieving a neuroprotective effect. This study demonstrates that salidroside can inhibit the activation of microglia by inducing GSK3β phosphorylation, achieve neuroprotective effects and alleviate learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development of salidroside and the clinical application of Rhodiola rosea L.

水杨甙通过GSK3β抑制小胶质细胞的活化,从而改善低压氧小鼠血脑屏障的完整性和认知功能。
红景天中的活性成分水杨甙已成为预防和治疗缺氧性脑损伤的潜在治疗药物,但水杨甙的确切靶点和作用机制仍不清楚。该研究利用网络药理学、转录组测序等技术,探讨了水杨甙调节血脑屏障(BBB)功能保护体内缺氧性脑损伤的机制和靶点。利用大分子对接和分子生物学技术,探讨水杨梅苷缓解 BV2 细胞模型缺氧性脑损伤的分子机制。结果表明,水杨苷能缓解低压缺氧小鼠的学习记忆功能障碍和病理损伤,降低脑含水量,减轻炎症反应和氧化应激,有效逆转血清中的S100β,促进BBB修复。GSK3β是柳氮苷治疗缺氧性认知障碍的重要治疗靶点,柳氮苷能特异性结合GSK3β的ATP结合袋,诱导GSK3β磷酸化,靶向下游Nrf-2调节小胶质细胞活性,促进β-catenin的积累,从而抑制小胶质细胞活化,改善BBB完整性损伤,达到神经保护作用。本研究证明,水杨甙可通过诱导GSK3β磷酸化抑制小胶质细胞的活化,实现神经保护作用,缓解低压缺氧小鼠的学习记忆功能障碍。该研究为红景天苷的开发和临床应用提供了理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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