Futoquinol improves Aβ25–35-induced memory impairment in mice by inhibiting the activation of p38MAPK through the glycolysis pathway and regulating the composition of the gut microbiota,Phytotherapy Research

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Futoquinol improves Aβ25–35-induced memory impairment in mice by inhibiting the activation of p38MAPK through the glycolysis pathway and regulating the composition of the gut microbiota
Phytotherapy Research ( IF 6.1 ) Pub Date : 2024-02-08 , DOI: 10.1002/ptr.8136
Yuhan Zhang _{1,

2} , Hui Chen ₁ , Mengnan Zeng _{1,

2} , Pengli Guo _{1,

2} , Meng Liu _{1,

2} , Bing Cao _{1,

2} , Ru Wang _{1,

2} , Fengxiao Hao _{1,

2} , Xiaoke Zheng _{1,

2} , Weisheng Feng _{1,

2}

Affiliation

Futoquinol (Fut) is a compound extracted from Piper kadsura that has a nerve cell protection effect. However, it is unclear whether Fut has protective effects in Alzheimer's disease (AD). In this study, we aimed to explore the therapeutic effect of Fut in AD and its underlying mechanism. UPLC-MS/MS method was performed to quantify Fut in the hippocampus of mice brain. The cognition ability, neuronal and mitochondria damage, and levels of Aβ_1–42, Aβ_1–40, p-Tau, oxidative stress, apoptosis, immune cells, and inflammatory factors were measured in Aβ_25–35-induced mice. The content of bacterial meta-geometry was predicted in the microbial composition based on 16S rDNA. The protein levels of HK II, p-p38MAPK, and p38MAPK were detected. PC-12 cells were cultured in vitro, and glucose was added to activate glycolysis to further explore the mechanism of action of Fut intervention in AD. Fut improved the memory and learning ability of Aβ_25–35 mice, and reduced neuronal damage and the deposition of Aβ and Tau proteins. Moreover, Fut reduced mitochondrial damage, the levels of oxidative stress, apoptosis, and inflammatory factors. Fut significantly inhibited the expression of HK II and p-p38MAPK proteins. The in vitro experiment showed that p38MAPK was activated and Fut action inhibited after adding 10 mM glucose. Fut might inhibit the activation of p38MAPK through the glycolysis pathway, thereby reducing oxidative stress, apoptosis, and inflammatory factors and improving Aβ_25–35-induced memory impairment in mice. These data provide pharmacological rationale for Fut in the treatment of AD.

中文翻译：

Futoquinol 通过糖酵解途径抑制 p38MAPK 的激活并调节肠道微生物群的组成，从而改善 Aβ25-35 诱导的小鼠记忆障碍

Futoquinol (Fut) 是从五味子中提取的化合物，具有神经细胞保护作用。然而，目前尚不清楚 Fut 是否对阿尔茨海默病 (AD) 具有保护作用。在本研究中，我们旨在探讨Fut对AD的治疗作用及其潜在机制。采用UPLC-MS/MS方法定量小鼠大脑海马中的Fut。测量 Aβ _25-35诱导小鼠的认知能力、神经元和线粒体损伤以及 Aβ _1-42 、Aβ _1-40 、p-Tau 水平、氧化应激、细胞凋亡、免疫细胞和炎症因子。基于16S rDNA预测微生物组成中细菌元几何的含量。检测HK II、p-p38MAPK和p38MAPK的蛋白水平。体外培养PC-12细胞，添加葡萄糖激活糖酵解，进一步探讨Fut干预AD的作用机制。 Fut 改善了 Aβ _25-35小鼠的记忆和学习能力，并减少了神经元损伤以及 Aβ 和 Tau 蛋白的沉积。此外，Fut 还可以减少线粒体损伤、氧化应激、细胞凋亡和炎症因子的水平。 Fut显着抑制HK II和p-p38MAPK蛋白的表达。体外实验表明，加入10 mM葡萄糖后，p38MAPK被激活，Fut作用被抑制。 Fut 可能通过糖酵解途径抑制 p38MAPK 的激活，从而减少氧化应激、细胞凋亡和炎症因子，改善 Aβ _25-35诱导的小鼠记忆障碍。这些数据为 Fut 治疗 AD 提供了药理学原理。

更新日期：2024-02-08

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