Futoquinol improves Aβ 25-35 -induced memory impairment in mice by inhibiting the activation of p38MAPK through the glycolysis pathway and regulating the composition of the gut microbiota.

Autor: Zhang Y; College of pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, China., Chen H; College of pharmacy, Henan University of Chinese Medicine, Zhengzhou, China., Zeng M; College of pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, China., Guo P; College of pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, China., Liu M; College of pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, China., Cao B; College of pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, China., Wang R; College of pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, China., Hao F; College of pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, China., Zheng X; College of pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, China., Feng W; College of pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, China.
Jazyk: angličtina
Zdroj: Phytotherapy research : PTR [Phytother Res] 2024 Apr; Vol. 38 (4), pp. 1799-1814. Date of Electronic Publication: 2024 Feb 08.
DOI: 10.1002/ptr.8136
Abstrakt: 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.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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