AMY1受体信号级联在萝卜硫素对硝酸甘油诱导小鼠偏头痛的保护作用中的作用。

IF 3.6 3区 医学 Q2 CHEMISTRY, MEDICINAL
Luejine A. Elbendary, Ghada A. Abdel-Latif, Mohamed A. Khattab, Ayman E. El-Sahar, Rabab H. Sayed
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引用次数: 0

摘要

偏头痛是一种普遍的神经系统疾病,在女性中比在男性中更常见。三叉神经血管通路的激活和降钙素基因相关肽(CGRP)的释放是其发病机制的核心。值得注意的是,amylin和CGRP共享amyin -1 (AMY1)受体,该受体在涉及偏头痛机制的关键结构中表达。最近的研究强调了AMY1受体作为偏头痛治疗的一个有希望的治疗靶点。萝卜硫素是一种天然化合物,具有神经保护和抗炎作用,在这种情况下,它的潜在益处引起了人们的兴趣。本研究评估了萝卜硫素对硝酸甘油诱导的雌性小鼠偏头痛的保护作用,并将其与标准偏头痛药物托吡酯的疗效进行了比较。用硝酸甘油(10mg /kg, i.p.,每隔一天给药)诱导偏头痛,治疗包括萝卜硫素(5mg /kg/day, i.p.)或托吡酯(30mg /kg/day, i.p.),持续9天。萝卜硫素对畏光、头部梳理、机械和热异常性疼痛等行为症状有显著改善。这些行为变化伴随着血清一氧化氮、CGRP和促炎细胞因子水平的降低。组织学分析表明,萝卜硫素可改善硝酸甘油对三叉神经节和三叉尾核的损伤。此外,萝卜硫素降低了髓质中AMY1受体的表达,并抑制了其下游信号成分,包括磷酸化的ERK1/2、P38和c-Fos。萝卜硫素进一步增强Nrf2/HO-1通路,同时抑制NF-κB/NLRP3/caspase-1信号级联。研究结果表明,萝卜硫素可能通过调节AMY1受体相关信号通路,为偏头痛的治疗提供一种新的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Role of the AMY1 Receptor Signaling Cascade in the Protective Effect of Sulforaphane Against Nitroglycerin-Induced Migraine in Mice

Migraine is a prevalent neurological disorder that is more commonly observed in women than in men. The activation of trigeminal vascular pathways and the release of calcitonin gene-related peptide (CGRP) are central to its pathogenesis. Notably, amylin and CGRP share the amylin-1 (AMY1) receptor, which is expressed in key structures implicated in migraine mechanisms. Recent research has highlighted the AMY1 receptor as a promising therapeutic target for migraine treatment. Sulforaphane, a natural compound recognized for its neuroprotective and anti-inflammatory effects, has gained interest for its potential benefits in this context. This study evaluated the protective effects of sulforaphane against nitroglycerin induced migraine in female mice, comparing its efficacy to the standard migraine medication, topiramate. Migraine was induced using nitroglycerin (10 mg/kg, i.p., administered every other day), and treatments included sulforaphane (5 mg/kg/day, i.p.) or topiramate (30 mg/kg/day, i.p.) for a duration of 9 days. Sulforaphane demonstrated significant improvements in behavioral symptoms such as photophobia, head grooming, and both mechanical and thermal allodynia. These behavioral changes were accompanied by reductions in serum levels of nitric oxide, CGRP, and pro-inflammatory cytokines. Histological analysis revealed that sulforaphane ameliorated nitroglycerin induced damage in the trigeminal ganglia and trigeminal nucleus caudalis. Additionally, sulforaphane reduced AMY1 receptor expression in the medulla and inhibited its downstream signaling components, including phosphorylated ERK1/2, P38, and c-Fos. Sulforaphane further enhanced the Nrf2/HO-1 pathway while suppressing the NF-κB/NLRP3/caspase-1 signaling cascade. The findings suggest that sulforaphane may offer a novel therapeutic approach for managing migraines by modulating AMY1 receptor-related signaling pathways.

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来源期刊
Archiv der Pharmazie
Archiv der Pharmazie 医学-化学综合
CiteScore
7.90
自引率
5.90%
发文量
176
审稿时长
3.0 months
期刊介绍: Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.
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