Puerarin suppresses the oxidative stress and activates the cyclic AMP (cAMP)/cAMP response element binding protein/brain-derived neurotrophic factor signaling pathway in alcohol withdrawal-induced depressive disorder via regulating obesity-associated protein-mediated N6-methyladenosine demethylation.

IF 1.6 4区医学 Q4 NEUROSCIENCES

Neuroreport Pub Date : 2025-08-06 Epub Date: 2025-06-03 DOI:10.1097/WNR.0000000000002179

Yazhong Li, Zhong Liu, Jianhua Ma, Aizhao Tian, Jia Wang, Yang Xu, Jie Yang, Xin Yan

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引用次数: 0

Abstract

Objective: Puerarin, a bioactive isoflavone glycoside predominantly extracted from the root of the kudzu plant ( Pueraria lobata ), is a traditional Chinese medicinal herb widely used for centuries. Alcohol withdrawal-induced depression (AWIDD), a serious psychiatric disorder, is prevalent in society. This study aimed to investigate the role of puerarin in oxidative stress and cyclic AMP (cAMP)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in AWIDD, as well as the underlying mechanism.

Methods: An alcohol withdrawal rat model was established. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-px) were measured using commercial kits. The cAMP level was detected by ELISA. CREB and phospho-CREB protein levels were analyzed by Western blot. BDNF level was assessed by reverse transcription-quantitative PCR. Dot blot was used to assess the total N6-methyladenosine (m 6 A) level. The interaction between obesity-associated protein (FTO) and prostaglandin-endoperoxide synthase 1 (PTGS1) was examined through RNA immunoprecipitation and dual-luciferase reporter assays.

Results: Puerarin decreased oxidative stress and increased the cAMP, p-CREB, and BDNF levels. Besides, puerarin increased FTO-mediated m 6 A demethylation in alcohol withdrawal rats. FTO inhibition increased oxidative stress and decreased the activation of cAMP/CREB/BDNF signaling pathway. Mechanistically, FTO weakened the stability of PTGS1 mRNA via m 6 A demethylation. Overexpression of PTGS1 reversed the reduction in oxidative stress and the activation of the cAMP/CREB/BDNF signaling pathway induced by FTO overexpression.

Conclusion: Puerarin suppressed oxidative stress and activated the cAMP/CREB/BDNF signaling pathway in AWIDD via regulating FTO-mediated m 6 A demethylation.

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葛根素通过调节肥胖相关蛋白介导的n6 -甲基腺苷去甲基化，抑制酒精戒断性抑郁症的氧化应激，激活环AMP (cAMP)/cAMP反应元件结合蛋白/脑源性神经营养因子信号通路。

目的：葛根素是一种具有生物活性的异黄酮苷，主要从葛根植物（葛根）的根中提取，是一种被广泛使用了几个世纪的传统中药。酒精戒断性抑郁症（AWIDD）是一种严重的精神疾病，在社会上十分普遍。本研究旨在探讨葛根素在AWIDD氧化应激和环AMP (cAMP)/cAMP反应元件结合蛋白(CREB)/脑源性神经营养因子（BDNF）信号通路中的作用及其机制。方法：建立酒精戒断大鼠模型。超氧化物歧化酶（SOD）、丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-px）水平采用商用试剂盒测定。ELISA法检测cAMP水平。Western blot分析CREB和磷酸化CREB蛋白水平。采用逆转录-定量PCR检测BDNF水平。Dot blot法检测总n6 -甲基腺苷（m6A）水平。通过RNA免疫沉淀和双荧光素酶报告基因检测，研究肥胖相关蛋白（FTO）与前列腺素内过氧化物合成酶1 （PTGS1）的相互作用。结果：葛根素降低氧化应激，提高cAMP、p-CREB、BDNF水平。此外，葛根素增加酒精戒断大鼠fto介导的m6A去甲基化。FTO抑制增加氧化应激，降低cAMP/CREB/BDNF信号通路的激活。机制上，FTO通过m6A去甲基化削弱了PTGS1 mRNA的稳定性。PTGS1的过表达逆转了FTO过表达诱导的氧化应激的减少和cAMP/CREB/BDNF信号通路的激活。结论：葛根素通过调控fto介导的m6A去甲基化，抑制AWIDD的氧化应激，激活cAMP/CREB/BDNF信号通路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroreport 医学-神经科学

CiteScore

3.20

自引率

0.00%

发文量

150

审稿时长

1 months

期刊介绍： NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.