神经炎症被认为在阿尔茨海默病（AD）发病机制中具有重要作用。小胶质细胞是中枢神经系统的驻留巨噬细胞，调节小胶质细胞的活化是预防AD的一种有前景的策略。茉莉花（Jasminum grandiflorum L.）精油在民间药物中常用于缓解精神压力和疾病，并通过分析揭示其挥发性化合物和评价JGEO对小胶质细胞过度活化的抑制作用，以实现其应用价值。本研究旨在探索JGEO中用于治疗AD的潜在活性化合物，通过抑制小胶质细胞活化与网络药理学、分子对接和小胶质细胞模型进行研究。采用顶空固相微萃取结合气相色谱-质谱分析法，分析了50℃、70℃、90℃和100℃下提取J. grandiflorum L.花的化合物的挥发特性，每个温度下提取50分钟。网络药理学分析和分子对接技术根据检出的JGEO化合物预测关键化合物、关键靶点和结合能。在脂多糖（LPS）诱导的BV-2细胞模型中，细胞经LPS处理后与JGEO以7.5μg/mL、15.0μg/mL和30μg/mL浓度处理，分析细胞形态学变化、一氧化氮（NO）和活性氧的产生以及BV-2细胞肿瘤坏死因子-α、白细胞介素-1β和电离钙结合适配体分子1表达。通过检测，共鉴定了34种挥发性差异显著的化合物。α-己基肉桂醛、内鲁酮、六氢芳烯甲酮、十二缩醛和癸醛被预测为前五个关键化合物，SRC、EGFR、VEGFA、HSP90AA1和ESR1被预测为前五个关键靶点。此外，它们之间的结合能低于-3.9 kcal/mol。BV-2细胞经LPS活化出现形态学变化，JGEO不仅可以明显逆转这些变化，而且能显著抑制NO和活性氧的产生，抑制肿瘤坏死因子-α、白细胞介素-1β和电离钙结合适配体分子1的表达。研究结果表明，JGEO可以通过多组分、多靶点的作用方式抑制小胶质细胞的过度活化，降低神经炎症和氧化应激反应，从而支持传统上使用JGEO来治疗与神经炎症相关的疾病。版权所有© 2023 Lu、Zeng、Feng、Li、Wang、Liu、Chen、Guan、Chen和Wei。

Neuroinflammation is considered to have a prominent role in the pathogenesis of Alzheimer's disease (AD). Microglia are the resident macrophages of the central nervous system, and modulating microglia activation is a promising strategy to prevent AD. Essential oil of Jasminum grandiflorum L. flowers is commonly used in folk medicine for the relief of mental pressure and disorders, and analyzing the volatile compound profiles and evaluating the inhibitory effects of J. grandiflorum L. essential oil (JGEO) on the excessive activation of microglia are valuable for its application. This study aims to explore the potential active compounds in JGEO for treating AD by inhibiting microglia activation-integrated network pharmacology, molecular docking, and the microglia model. A headspace solid-phase microextraction combined with the gas chromatography-mass spectrometry procedure was used to analyze the volatile characteristics of the compounds in J. grandiflorum L. flowers at 50°C, 70°C, 90°C, and 100°C for 50 min, respectively. A network pharmacological analysis and molecular docking were used to predict the key compounds, key targets, and binding energies based on the detected compounds in JGEO. In the lipopolysaccharide (LPS)-induced BV-2 cell model, the cells were treated with 100 ng/mL of LPS and JGEO at 7.5, 15.0, and 30 μg/mL, and then, the morphological changes, the production of nitric oxide (NO) and reactive oxygen species, and the expressions of tumor necrosis factor-α, interleukin-1β, and ionized calcium-binding adapter molecule 1 of BV-2 cells were analyzed. A total of 34 compounds with significantly different volatilities were identified. α-Hexylcinnamaldehyde, nerolidol, hexahydrofarnesyl acetone, dodecanal, and decanal were predicted as the top five key compounds, and SRC, EGFR, VEGFA, HSP90AA1, and ESR1 were the top five key targets. In addition, the binding energies between them were less than -3.9 kcal/mol. BV-2 cells were activated by LPS with morphological changes, and JGEO not only could clearly reverse the changes but also significantly inhibited the production of NO and reactive oxygen species and suppressed the expressions of tumor necrosis factor-α, interleukin-1β, and ionized calcium-binding adapter molecule 1. The findings indicate that JGEO could inhibit the overactivation of microglia characterized by decreasing the neuroinflammatory and oxidative stress responses through the multi-compound and multi-target action modes, which support the traditional use of JGEO in treating neuroinflammation-related disorders.Copyright © 2023 Lu, Zeng, Feng, Li, Wang, Liu, Chen, Guan, Chen and Wei.