Liu Qi, Yan Ruijie, Wang Ling, Li Rui, Zhang Di, Liao Can, Mao Shengjun
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
Neuropharmacology. 2024 Dec 15;261:110158. doi: 10.1016/j.neuropharm.2024.110158. Epub 2024 Sep 12.
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.
偏头痛是一种高度流行的神经系统疾病。α-细辛脑（ASA）是石菖蒲中发现的一种主要活性成分，在神经性疼痛的镇痛和抗炎方面发挥着关键作用。本研究旨在评估ASA对偏头痛的疗效，并使用成熟的炎症介质（IS）偏头痛雌性大鼠模型阐明其潜在机制。在注入IS前每天评估机械性疼痛阈值，随后给予ASA注入后给药。随后，在最后一次给药后，对自发运动活动、探索行为、短期空间记忆和畏光进行盲法评估。然后处死大鼠以研究其潜在的作用机制。还采用网络药理学预测ASA抗偏头痛的潜在靶点和途径。在脂多糖（LPS）刺激的BV2细胞中检测ASA的抗炎活性和途径相关蛋白。结果表明，ASA改善了IS大鼠的皮肤痛觉过敏和畏光，同时改善了空间记忆并增加了探索行为。ASA减弱了与中枢敏化相关的指标和过高的谷氨酸水平，同时增强了GABA合成。ASA挽救了IS大鼠皮层和海马中的神经元损失。值得注意的是，一线治疗药物舒马曲坦未观察到ASA在Y迷宫试验中改善空间记忆表现的能力，这表明TLR4途径可能参与其中。此外，ASA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。总体而言，ASA通过抑制过度兴奋和小胶质细胞相关炎症，显示出缓解偏头痛大鼠痛觉过敏和改善行为表现的潜力。
