Alpha-asarone alleviates cutaneous hyperalgesia by inhibiting hyperexcitability and neurogenic inflammation via TLR4/NF-κB/NLRP3 signaling pathway in a female chronic migraine rat model

IF 4.6 2区 医学 Q1 NEUROSCIENCES Neuropharmacology Pub Date : 2024-09-12 DOI:10.1016/j.neuropharm.2024.110158
Qi Liu, Ruijie Yan, Ling Wang, Rui Li, Di Zhang, Can Liao, Shengjun Mao
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Abstract

Migraine is a highly prevalent neurological disorder. Alpha-asarone (ASA), a major active component found in Acorus tatarinowii, plays a crucial role in analgesia and anti-inflammation for neuropathic pain. This study aimed to assess the efficacy of ASA against migraine and elucidate its potential mechanisms using a well-established inflammatory soup (IS) migraine female rat model. Mechanical pain thresholds were assessed daily before IS infusion, followed by post-infusion administration of ASA. Subsequently, spontaneous locomotor activities, exploratory behavior, short-term spatial memory, and photophobia were blindly evaluated after the final drug administration. The rats were then sacrificed for investigation into the underlying mechanisms of action. Network pharmacology was also employed to predict potential targets and pathways of ASA against migraine. The anti-inflammatory activity of ASA and pathway-related proteins were examined in BV2 cells stimulated with lipopolysaccharides (LPS). The results demonstrated that ASA ameliorated cutaneous hyperalgesia and photophobia while improving spatial memory and increasing exploratory behavior in IS rats. ASA attenuated central sensitization-related indicators and excessive glutamate levels while enhancing GABA synthesis. ASA rescued neuronal loss in the cortex and hippocampus of IS rats. Notably, the ability of ASA to improve spatial memory performance in the Y maze test was not observed with sumatriptan, a first-line treatment drug, suggesting the potential involvement of the TLR4 pathway. Moreover, ASA suppressed microglial activation, reduced pro-inflammatory factors, and downregulated TLR4, MyD88, p–NF–κB/NF-κB, NLRP3, caspase-1, IL-1β, and IL-18. Overall, ASA demonstrated its potential to alleviate hyperalgesia and improve behavioral performance in migraine rats by inhibiting hyperexcitability and microglia-related inflammation.

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在雌性慢性偏头痛大鼠模型中,α-asarone通过TLR4/NF-κB/NLRP3信号通路抑制过度兴奋和神经源性炎症,从而减轻皮肤痛觉减退症状
偏头痛是一种高发的神经系统疾病。鞑靼藜(Acorus tatarinowii)中的主要活性成分α-asarone(ASA)在镇痛和抗炎方面对神经性疼痛起着至关重要的作用。本研究旨在使用一种成熟的炎症汤(IS)偏头痛雌性大鼠模型,评估ASA对偏头痛的疗效并阐明其潜在机制。每天在输注 IS 前评估机械痛阈值,然后在输注后注射 ASA。随后,在最后一次给药后对大鼠的自发运动活动、探索行为、短期空间记忆和畏光进行盲法评估。大鼠随后被处死,以研究其潜在的作用机制。研究人员还利用网络药理学预测了ASA对抗偏头痛的潜在靶点和途径。研究人员在受到脂多糖(LPS)刺激的BV2细胞中检测了ASA和通路相关蛋白的抗炎活性。结果表明,ASA能改善IS大鼠的皮肤痛觉减退和畏光症状,同时改善空间记忆和增加探索行为。ASA 可减轻中枢敏化相关指标和过高的谷氨酸水平,同时增强 GABA 的合成。ASA 挽救了 IS 大鼠大脑皮层和海马的神经元损失。值得注意的是,ASA能改善Y迷宫测试中的空间记忆能力,而一线治疗药物舒马曲坦(sumatriptan)却无法做到这一点,这表明TLR4通路可能参与其中。此外,ASA 还能抑制小胶质细胞活化,减少促炎因子,并下调 TLR4、MyD88、p-NF-κB/NF-κB、NLRP3、caspase-1、IL-1β 和 IL-18。总之,ASA 通过抑制过度兴奋和与小胶质细胞相关的炎症,证明了其缓解偏头痛大鼠痛觉过度和改善行为表现的潜力。
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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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