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酸枣仁通过靶向FAK-DOCK180-Rac1-WAVE2-Arp3信号通路减轻脂多糖诱导的血脑屏障功能障碍。

Semen Ziziphi Spinosae attenuates blood-brain barrier dysfunction induced by lipopolysaccharide by targeting the FAK-DOCK180-Rac1-WAVE2-Arp3 signaling pathway.

作者信息

Liu Huayan, Zhang Xin, Liu Yujiao, Xin Nian, Deng Yulin, Li Yujuan

机构信息

School of Life Science, Beijing Institute of Technology, 100081, Beijing, China.

BIT&GS Technologies Co. Ltd, 100074, Beijing, China.

出版信息

NPJ Sci Food. 2022 Jun 2;6(1):27. doi: 10.1038/s41538-022-00142-6.

DOI:10.1038/s41538-022-00142-6
PMID:35655066
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9163036/
Abstract

Semen Ziziphi Spinosae (SZS) has been extensively used in the daily diet as a functional food for neuroprotective health-benefit in China for many years. However, the neuroprotective mechanism of SZS associated with blood-brain barrier (BBB) integrity remains unexplored. The present study suggests SZS could protect against lipopolysaccharide (LPS)-induced BBB dysfunction. Proteomics indicate that 135 proteins in rat brain are significantly altered by SZS. These differentially expressed proteins are mainly clustered into cell-cell adhesion and adherens junctions, which are closely related with BBB integrity. SZS reversed LPS-induces BBB breakdown by activating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway. Molecular docking between signaling pathway proteins and identified SZS components in rat plasma reveals that 6"'-feruloylspinosin, spinosin, and swertisin strongly binds to signaling proteins at multiple amino acid sites. These novel findings suggest a health benefit of SZS in prevention of cerebral diseases and contributes to the further application of SZS as a functional food.

摘要

酸枣仁在中国多年来一直被广泛用作日常饮食中的功能性食品,具有神经保护健康益处。然而,酸枣仁与血脑屏障(BBB)完整性相关的神经保护机制仍未被探索。本研究表明酸枣仁可以保护免受脂多糖(LPS)诱导的血脑屏障功能障碍。蛋白质组学表明,大鼠脑中135种蛋白质因酸枣仁而发生显著变化。这些差异表达的蛋白质主要聚集在细胞间粘附和粘着连接中,这与血脑屏障的完整性密切相关。酸枣仁通过激活FAK-DOCK180-Rac1-WAVE2-Arp3途径逆转LPS诱导的血脑屏障破坏。信号通路蛋白与大鼠血浆中鉴定出的酸枣仁成分之间的分子对接表明,6''-阿魏酰斯皮诺素、斯皮诺素和獐牙菜苷在多个氨基酸位点与信号蛋白强烈结合。这些新发现表明酸枣仁在预防脑部疾病方面具有健康益处,并有助于酸枣仁作为功能性食品的进一步应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f4/9163036/438d3d71fb65/41538_2022_142_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f4/9163036/6bd35b01d041/41538_2022_142_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f4/9163036/4cc388f7a2fb/41538_2022_142_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f4/9163036/374ce304b190/41538_2022_142_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f4/9163036/9fb61618ffa3/41538_2022_142_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f4/9163036/438d3d71fb65/41538_2022_142_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f4/9163036/6bd35b01d041/41538_2022_142_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f4/9163036/4cc388f7a2fb/41538_2022_142_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f4/9163036/374ce304b190/41538_2022_142_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f4/9163036/9fb61618ffa3/41538_2022_142_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f4/9163036/438d3d71fb65/41538_2022_142_Fig5_HTML.jpg

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