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红花黄色素通过调节胆碱能系统功能、氧化应激和CREB/BDNF/TrkB信号通路减轻小鼠的认知障碍。

Safflower yellow alleviates cognitive impairment in mice by modulating cholinergic system function, oxidative stress, and CREB/BDNF/TrkB signaling pathway.

作者信息

Qi Yanqiang, Wang Yanyou, Ni Mingyue, He Yingxi, Li Le, Hu Yanli

机构信息

Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Department of Pharmacology, Shihezi University, Shihezi, 832000, Xinjiang, People's Republic of China; Department of Pharmacy, The First People's Hospital of Xianyang, Xianyang, 712000, Shaanxi, People's Republic of China.

Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Department of Pharmacology, Shihezi University, Shihezi, 832000, Xinjiang, People's Republic of China.

出版信息

J Ethnopharmacol. 2025 Jan 31;340:118986. doi: 10.1016/j.jep.2024.118986. Epub 2024 Oct 24.

DOI:10.1016/j.jep.2024.118986
PMID:39461389
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Carthamus tinctorius L. (Safflower) was believed to have multiple benefits, including antioxidant effects, enhanced learning and memory, and improving neuronal injury. Safflower Yellow(SY) are the main active ingredients of Safflower, displays strong pharmacological potential treatment of Alzheimer's disease(AD). However, its effect on memory impairments remains insufficiently investigated.

AIM OF THE STUDY

The study aims to investigate the effects of SY on cognitive functions in memory impairments model and to explore the mechanism of its action.

MATERIALS AND METHODS

We utilized the Morris Water Maze, Step-Through Test, Step-Down Test to assess the potential of SY in ameliorating learning and memory dysfunction caused by SCOP, NaNO and ethanol in mice. Bioinformatic analysis and molecular biological approaches were used to study the related mechanisms of SY on anti-memory impairments.

RESULTS

The results of the Morris Water Test suggested that SY could shorten the escape latency and the time of the first crossing platform in the mice with memory acquisition and memory consolidation impairments, and increase the platform crossing times. The results of the Step-Though test and Step-Down test showed that the escape latency in the mice was prolonged and the number of errors was reduced after SY treatment. ELISA experiments indicated that SY decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress markers (SOD, MDA, and GSH-PX) in scopolamine-induced mice. Western Blot and Nissl staining showed that SY could activated BDNF/TrkB/CREB signaling pathway and reduced neuronal damage.

CONCLUSION

The findings present that SY can restore the function of the cholinergic system, inhibit oxidative stress, regulate the expression of upstream and downstream proteins in the CREB/BDNF/TrkB pathway, and alleviate brain tissue damage to improve memory impairment in mice.

摘要

民族药理学相关性

人们认为红花(Carthamus tinctorius L.)具有多种益处,包括抗氧化作用、增强学习和记忆能力以及改善神经元损伤。红花黄色素(SY)是红花的主要活性成分,显示出对阿尔茨海默病(AD)具有强大的药理治疗潜力。然而,其对记忆障碍的影响仍未得到充分研究。

研究目的

本研究旨在探讨SY对记忆障碍模型认知功能的影响,并探讨其作用机制。

材料与方法

我们利用莫里斯水迷宫、穿梭箱试验、跳台试验来评估SY改善由东莨菪碱、亚硝酸钠和乙醇引起的小鼠学习和记忆功能障碍的潜力。采用生物信息学分析和分子生物学方法研究SY抗记忆障碍的相关机制。

结果

莫里斯水试验结果表明,SY可以缩短记忆获取和记忆巩固受损小鼠的逃避潜伏期和首次穿越平台的时间,并增加穿越平台的次数。穿梭箱试验和跳台试验结果表明,SY处理后小鼠的逃避潜伏期延长,错误次数减少。ELISA实验表明,SY降低了东莨菪碱诱导小鼠的乙酰胆碱酯酶活性,增加了胆碱乙酰转移酶活性,并调节了氧化应激标志物(超氧化物歧化酶、丙二醛和谷胱甘肽过氧化物酶)。蛋白质免疫印迹和尼氏染色表明,SY可以激活脑源性神经营养因子/酪氨酸激酶B/环磷腺苷效应元件结合蛋白信号通路并减少神经元损伤。

结论

研究结果表明,SY可以恢复胆碱能系统的功能,抑制氧化应激,调节CREB/脑源性神经营养因子/酪氨酸激酶B通路上下游蛋白的表达,并减轻脑组织损伤,从而改善小鼠的记忆障碍。

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