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染料木黄酮缓解硝化甘油诱导的偏头痛:一氧化氮介导的血管舒张和氧化应激的调节。

Genistein mitigates nitroglycerine-induced migraine: modulation of nitric oxide-mediated vasodilation and oxidative stress.

机构信息

University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, 140413, India.

Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.

出版信息

Metab Brain Dis. 2024 Jun;39(5):821-831. doi: 10.1007/s11011-024-01360-5. Epub 2024 May 25.

DOI:10.1007/s11011-024-01360-5
PMID:38795260
Abstract

Migraine is a widespread brain condition described by frequent, recurrent episodes of incapacitating, moderate-to-severe headaches with throbbing pain that are usually one-sided. It is the 2nd most debilitating state lived with disability in terms of years, with a prevalence rate of 15-20%. Significant drops in estrogen levels have been associated with triggering acute migraine attacks in certain cases. Phytoestrogens are plant-derived compounds that resemble estrogen in structure, enabling them to imitate estrogen's functions in the body by attaching to estrogen receptors. Thus, the study was aimed to explore the protective effect of genistein against migraine. Moreover, the role of nitric oxide was also studied in the observed effect of genistein. Nitric oxide (NO) is implicated in migraine pathophysiology due to its role in promoting cerebral vasodilation and modulation of pain perception. Exploring L-NAME, a nitric oxide synthase inhibitor in migraine research helps scientists better understand the role of NO in migraine. Nitroglycerine treatment significantly increased the facial-unilateral head pain and spontaneous pain, as evidenced by the increased number of head scratching and groomings. Nitroglycerine treatment also induced anxiogenic behavior in mice. A significant reduction in the number of entries in the light phase and open arm, respectively. Biochemical analysis indicated a significant increase in inflammatory and oxidative stress in the nitroglycerin group. A significant increase and decrease in brain TBARS and GSH were observed with nitroglycerine treatment, respectively. Moreover, nitroglycerine treatment has uplifted the serum TNF-α level. Genistein (20 mg/kg) significantly mitigated the facial-unilateral head pain, spontaneous pain, photophobia, and anxiety-like behavior induced by nitroglycerine. Biochemical analysis showed that genistein (20 mg/kg) significantly abrogated the nitroglycerine-induced lipid peroxidation and increased serum TNF-α level. Genistein treatment also upregulated the brain GSH level and downregulated the serum TNF-α level. The L-NAME-mediated alleviation of the protective effect of genistein might be attributed to the vasodilatory effect of L-NAME. Conclusively, it can be suggested that genistein might provide relief from migraine pain by inhibiting nitric oxide-mediated vasodilation and oxidative stress.

摘要

偏头痛是一种广泛存在的脑部疾病,其特征是频繁、反复发作使人丧失能力的中度至重度头痛,伴有搏动性疼痛,通常是单侧的。偏头痛是继身体残疾导致丧失能力的第二大严重疾病,其患病率为 15-20%。在某些情况下,雌激素水平的显著下降与急性偏头痛发作的触发有关。植物雌激素是结构上类似于雌激素的植物衍生化合物,它们通过与雌激素受体结合,能够模拟雌激素在体内的功能。因此,本研究旨在探索染料木黄酮对偏头痛的保护作用。此外,还研究了一氧化氮在染料木黄酮观察到的作用中的作用。一氧化氮(NO)在偏头痛发病机制中起作用,因为它促进脑血管扩张并调节疼痛感知。在偏头痛研究中探索一氧化氮合酶抑制剂 L-NAME 有助于科学家更好地了解 NO 在偏头痛中的作用。硝化甘油治疗显著增加了面部单侧头痛和自发性疼痛,这表现为头搔抓和梳理次数的增加。硝化甘油治疗还诱导了小鼠的焦虑行为。在亮相和开放臂中分别显著减少进入次数。生化分析表明,硝化甘油组的炎症和氧化应激显著增加。用硝化甘油处理观察到大脑 TBARS 和 GSH 分别显著增加和减少。此外,硝化甘油治疗使血清 TNF-α水平升高。染料木黄酮(20mg/kg)显著减轻了硝化甘油引起的面部单侧头痛、自发性疼痛、畏光和焦虑样行为。生化分析表明,染料木黄酮(20mg/kg)显著阻断了硝化甘油引起的脂质过氧化,并增加了血清 TNF-α水平。染料木黄酮处理还上调了大脑 GSH 水平并下调了血清 TNF-α水平。L-NAME 介导的染料木黄酮保护作用的缓解可能归因于 L-NAME 的血管扩张作用。总之,可以认为染料木黄酮通过抑制一氧化氮介导的血管扩张和氧化应激来缓解偏头痛疼痛。

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Curr Top Med Chem. 2023;23(15):1395-1413. doi: 10.2174/1568026623666230103163023.
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Effect of soy isoflavones supplementation on migraine characteristics, mental status and calcitonin gene-related peptide (CGRP) levels in women with migraine: results of randomised controlled trial.大豆异黄酮补充剂对偏头痛特征、精神状态和降钙素基因相关肽(CGRP)水平的影响:随机对照试验的结果。
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P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine.
P2X7R/NLRP3 信号通路介导的细胞焦亡和神经炎症导致偏头痛小鼠模型认知功能障碍。
J Headache Pain. 2022 Jul 2;23(1):75. doi: 10.1186/s10194-022-01442-8.
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Headache provocation by nitric oxide in men who have never experienced a headache.男性从未经历过头痛者中一氧化氮引起的头痛。
Cephalalgia. 2022 Jun;42(7):598-607. doi: 10.1177/03331024211060002. Epub 2021 Dec 7.
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Role of Neuroinflammation and Blood-Brain Barrier Permutability on Migraine.神经炎症和血脑屏障通透性在偏头痛中的作用。
Int J Mol Sci. 2021 Aug 19;22(16):8929. doi: 10.3390/ijms22168929.
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