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2-(3,4-Dihydroxyphenyl)ethyl 3-hydroxybutanoate Ameliorates Cognitive Dysfunction and Inflammation Via Modulating Gut Microbiota in Aged Senescence-Accelerated Mouse Prone8 Mice
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences ( IF 4.3 ) Pub Date : 2024-08-30 , DOI: 10.1093/gerona/glae220
Le Shi 1 , Peipei Gao 2 , Yue Zhang 1 , Quanyu Liu 1 , Ranrui Hu 1 , Zhuang Zhao 1 , Yachong Hu 1 , Xiaohong Xu 3 , Yehua Shen 4 , Jiankang Liu 1, 5 , Jiangang Long 1
Affiliation  

Numerous studies have indicated a close association between gut microbiota dysbiosis, inflammation, and cognitive impairment, highlighting their crucial role in the aging process. 2-(3,4-Dihydroxyphenyl)ethyl 3-hydroxybutanoate (HTHB), a novel derivative of hydroxytyrosol, known for its metabolic and anti-inflammatory properties, was investigated for its effects on memory, inflammation, and gut microbiota in senescence-accelerated mouse prone 8 mice. The study employed behavioral testing, biochemical detection, and 16S RNA analysis. Results revealed that HTHB mitigated memory decline and lymphocyte aberrance, reduced inflammation in the brain cortex, intestine and peripheral system, and modulated gut microbiota dysbiosis. Interestingly, the cognitive function and serum inflammation of mice significantly correlated with differences in gut microbiota in senescence-accelerated mouse prone 8 mice. Furthermore, HTHB treatment exhibited an enhancement of gut barrier integrity in colon tissue in SAMP8 mice. In vitro experiments using HCT116 and DLD1 cells further evidenced that HTHB rescued the tight junction protein levels impaired by lipopolysaccharide. These findings demonstrate that HTHB effectively ameliorates cognitive dysfunction in aged mice, by modulating gut microbiota, suppressing inflammation, and promoting intestinal barrier integrity. This highlights the potential of HTHB as a therapeutic agent for age-related cognitive loss.

中文翻译:


2-(3,4-二羟基苯基)3-羟基丁酸乙酯通过调节衰老加速小鼠 Prone8 小鼠的肠道微生物群改善认知功能障碍和炎症



大量研究表明,肠道微生物群失调、炎症和认知障碍之间存在密切关联,突出了它们在衰老过程中的关键作用。2-(3,4-二羟基苯基)3-羟基丁酸乙酯 (HTHB) 是羟基酪醇的新型衍生物,以其代谢和抗炎特性而闻名,研究了其对衰老加速小鼠易感 8 小鼠的记忆、炎症和肠道微生物群的影响。该研究采用了行为测试、生化检测和 16S RNA 分析。结果显示,HTHB 减轻了记忆力下降和淋巴细胞异常,减少了大脑皮层、肠道和外周系统的炎症,并调节了肠道菌群失调。有趣的是,小鼠的认知功能和血清炎症与衰老加速小鼠易感 8 小鼠肠道菌群的差异显著相关。此外,HTHB 治疗在 SAMP8 小鼠结肠组织中表现出肠道屏障完整性的增强。使用 HCT116 和 DLD1 细胞的体外实验进一步证明,HTHB 挽救了受脂多糖损害的紧密连接蛋白水平。这些发现表明,HTHB 通过调节肠道菌群、抑制炎症和促进肠道屏障完整性,有效改善老年小鼠的认知功能障碍。这突出了 HTHB 作为治疗年龄相关认知丧失的药物的潜力。
更新日期:2024-08-30
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