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葛根素通过修复肠道黏膜屏障缓解老年小鼠的睡眠障碍。

Puerarin alleviates sleep disorders in aged mice related to repairing intestinal mucosal barrier.

作者信息

Tao Qing, Zhang Jinhua, Liang Qiao, Song Shiyu, Wang Shuxia, Yao Xiaoming, Gao Qian, Wang Lei

机构信息

Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, 210093, Jiangsu, China.

Department of Clinical Laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, China.

出版信息

Nat Prod Bioprospect. 2023 Sep 12;13(1):29. doi: 10.1007/s13659-023-00390-3.

Abstract

More and more evidence suggests that puerarin, a potential remedy for gut inflammation, may have an ameliorative effect on sleep disturbances. However, the relationship between puerarin and sleep disruption has not been extensively researched. This study aims to explore the role and mechanisms of puerarin in improving sleep disorders. We established a light-induced sleep disorder model in mice and assessed the effects of puerarin on cognitive behavior using open field and water maze tests. Pathological detection demonstrated that sleep disturbances resulted in observable damage to the liver, lung, and kidney. Puerarin reversed multi-organ damage and inflammation. Further, puerarin activated paneth cells, resulting in increased lysozyme and TGF-β production, and stimulating intestinal stem cell proliferation. Puerarin also effectively inhibited the expression of F4/80, iNOS, TNF-α, and IL-1β in the small intestine, while it increased Chil3, CD206, and Arg-1 levels. Moreover, puerarin treatment significantly decreased P-P65, TLR4, Bcl-xl, and cleaved caspase-3 protein levels while increasing barrier protein levels, including ZO-1, Occludin, Claudin 1 and E-cadherin suggesting a reduction in inflammation and apoptosis in the gut. Overall, puerarin diminished systemic inflammation, particularly intestinal inflammation, and enhanced intestinal barrier integrity in mice with sleep disorders. Our findings suggest a potential new therapeutic pathway for sleep disorders.

摘要

越来越多的证据表明,葛根素作为一种潜在的肠道炎症治疗药物,可能对睡眠障碍具有改善作用。然而,葛根素与睡眠障碍之间的关系尚未得到广泛研究。本研究旨在探讨葛根素在改善睡眠障碍中的作用及机制。我们在小鼠中建立了光诱导睡眠障碍模型,并使用旷场试验和水迷宫试验评估了葛根素对认知行为的影响。病理检测表明,睡眠障碍导致肝脏、肺和肾脏出现明显损伤。葛根素逆转了多器官损伤和炎症。此外,葛根素激活了潘氏细胞,导致溶菌酶和转化生长因子-β的产生增加,并刺激肠道干细胞增殖。葛根素还有效抑制了小肠中F4/80、诱导型一氧化氮合酶、肿瘤坏死因子-α和白细胞介素-1β的表达,同时提高了Chil3、CD206和精氨酸酶-1的水平。此外,葛根素治疗显著降低了磷酸化P65、Toll样受体4、Bcl-xl和裂解的半胱天冬酶-3蛋白水平,同时增加了包括闭合蛋白-1、闭锁蛋白、Claudin 1和E-钙黏蛋白在内的屏障蛋白水平,表明肠道炎症和细胞凋亡减少。总体而言,葛根素减轻了全身炎症,特别是肠道炎症,并增强了睡眠障碍小鼠的肠道屏障完整性。我们的研究结果提示了一种潜在的睡眠障碍新治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9529/10497485/bee41e92d673/13659_2023_390_Fig1_HTML.jpg

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