背景：偏头痛是一种常见的神经血管疾病，具有典型的跳动和单侧头痛，对全球经济造成相当大的医疗负担。本研究旨在制备壳聚糖-海藻酸钠（CS-AL）纳米颗粒（NPs），其中含有佛首散油（FSSO），并研究其对偏头痛治疗的潜在疗效。 方法：采用单乳化溶剂蒸发法制备FSSO载药的CS-AL NPs。进一步使用脂多糖（LPS）刺激的BV-2细胞和硝酸甘油（NTG）诱导的偏头痛小鼠，探索该植物药物的抗偏头痛活性和潜在机制。结果：载药的FSSO- CS-AL NPs (212.1 ± 5.2nm, 45.1 ± 6.2 mV) 成球形状良好，具有持续的药物释放和良好的贮存性能，在4周内保持稳定。在LPS处理的BV-2细胞中，5μg/mL、10μg/mL和15μg/mL的FSSO和载药的FSSO- CS-AL NPs能通过降低肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和一氧化氮（NO）水平，提高白细胞介素-10（IL-10）表达，表现出抗炎活性。此外，载药的FSSO- CS-AL NPs (52和104mg/kg)能提高NTG诱导的偏头痛小鼠对热刺激的痛觉门槛，并减少乙酸诱导的扭动频率和搔脚时间。与模型组相比，5-羟色胺（5-HT）和内皮素（ET）水平上调，钙卡钙素基因相关肽（CGRP）和NO水平下调，ET/NO比例重新平衡，同时促进脑血流（CBF）以缓解血管运动功能障碍，这些变化发生在FSSO- CS-AL NPs (104mg/kg) 组。 结论：载药的FSSO- CS-AL NPs通过抑制LPS刺激的BV-2细胞中的神经炎症和调节NTG诱导的偏头痛小鼠中的血管活性物质，可缓解偏头痛。这些发现表明，FSS配方可能作为治疗偏头痛的新植物疗法被开发利用。版权所有©2023年 陈，成，曾和吕。

Background: Migraine is a common neurovascular disorder with typical throbbing and unilateral headaches, causing a considerable healthcare burden on the global economy. This research aims to prepare chitosan-alginate (CS-AL) nanoparticles (NPs) containing Foshousan oil (FSSO) and investigate its potential therapeutic effects on the treatment of migraine. Methods: FSSO-loaded CS-AL NPs were prepared by using the single emulsion solvent evaporation method. Lipopolysaccharide (LPS)-stimulated BV-2 cells and nitroglycerin (NTG)-induced migraine mice were further used to explore anti-migraine activities and potential mechanisms of this botanical drug. Results: FSSO-loaded CS-AL NPs (212.1 ± 5.2 nm, 45.1 ± 6.2 mV) had a well-defined spherical shape with prolonged drug release and good storage within 4 weeks. FSSO and FSSO-loaded CS-AL NPs (5, 10, and 15 μg/mL) showed anti-inflammatory activities in LPS-treated BV-2 cells via reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO), but elevating interleukin-10 (IL-10) expressions. Moreover, FSSO-loaded CS-AL NPs (52 and 104 mg/kg) raised pain thresholds against the hot stimulus and decreased acetic acid-induced writhing frequency and foot-licking duration in NTG-induced migraine mice. Compared with the model group, calcitonin gene-related peptide (CGRP) and NO levels were downregulated, but 5-hydroxytryptamine (5-HT) and endothelin (ET) levels were upregulated along with rebalanced ET/NO ratio, and vasomotor dysfunction was alleviated by promoting cerebral blood flow (CBF) in the FSSO-loaded CS-AL NPs (104 mg/kg) group. Conclusion: FSSO-loaded CS-AL NPs could attenuate migraine via inhibiting neuroinflammation in LPS-stimulated BV-2 cells and regulating vasoactive substances in NTG-induced migraine mice. These findings suggest that the FSS formula may be exploited as new phytotherapy for treating migraine.Copyright © 2023 Chen, Cheng, Zeng and Lv.