乳香没药精油自微乳的制备与抗炎镇痛作用评价

目的 制备乳香没药精油（FMO）自微乳化给药系统（FMO-SMEDDSs），并评价其抗炎镇痛效果。方法 水蒸气蒸馏法提取FMO，考察FMO与不同种类油相、乳化剂和助乳化剂的配伍相容性并确定了FMO-SMEDDSs的处方组成，最终根据伪三元相图法得到其处方配比；以热力学稳定性、动态光散射、透射电镜等实验手段评价FMO-SMEDDSs的理化性质。将 SD 大鼠随机分为 5 组 ：对照组、模型组、布洛芬（阳性药 ，20 mg·kg^-1）组、FMO（生药剂量 90 mg·kg^-1）组、FMOSMEDDSs （90 mg·kg^-1）组，每天ig给药2次，连续给药7 d，对照组与模型组ig生理盐水；除对照组外，其余4组大鼠均在右后足跖sc 40.0%甲醛溶液0.1 mL，6 h后用千分尺测量大鼠右后足厚度，并计算肿胀度和肿胀抑制率；ELISA试剂盒法分别检测致炎足足底组织中前列腺素E₂（PGE₂）水平，血清白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平。通过小鼠扭体法评价布洛芬（40 mg·kg^-1）组、FMO（180 mg·kg^-1）组、FMO-SMEDDSs（180 mg·kg^-1）的镇痛效果。结果 根据配伍相容性及伪三元相图结果，分别选择肉豆蔻酸异丙酯（IPM）、聚山梨酯 80 和异丙醇作为 FMO-SMEDDSs 的油相、乳化剂和助乳化剂，配比为 4∶4∶2；FMO-SMEDDSs形成的微乳平均粒径为（57.8±1.1）nm，PDI为（0.216±0.014），Zeta电位为（-11.5±0.05）mV，在透射电镜下可观察到微乳呈球状，FMO-SMEDDSs热力学稳定性良好。与模型组比较，布洛芬、FMO、FMOSMEDDSs组大鼠的致炎足肿胀度及肿胀率均显著降低（P＜0.05），PGE₂、TNF-α和IL-6水平显著降低（P＜0.05）；与FMO组比较，FMO-SMEDDSs组大鼠致炎足肿胀度及肿胀率进一步显著降低（P＜0.05），PGE₂、TNF-α和IL-6水平进一步显著降低（P＜0.05）。与模型组比较，ig布洛芬、FMO以及FMO-SMEDDSs后均能显著延长小鼠扭体反应潜伏期，显著减少15 min内的扭体次数（P＜0.05）；相对于FMO组，FMO-SMEDDSs抑制小鼠扭体反应作用更明显。结论 成功制备FMO-SMEDDSs，其具有良好的抗炎镇痛的作用。

Preparation of frankincense and myrrh essential oils self microemulsifying drug delivery systems and evaluation of its anti-inflammatory and analgesic effects

Objective To explore the effective components of Prunella vulgaris stem and leaf total phenols and their anti-inflammatory mechanisms based on UPLC-Q-TOF-MS/MS, network pharmacology, molecular docking, and molecular dynamics simulation. Methods UHPLC-Q-TOF-MS/MS was used to analyze the total phenols in the aqueous extract of Prunella vulgaris stem and leaf. Using databases such as Swiss Target Prediction, GeneCards, and OMIM to screen the target corresponding to the anti-inflammatory effect of Prunella vulgaris. The key target protein interaction (PPI) network was constructed using STRING database and Cytoscape software. GO function and KEGG signal pathway enrichment analysis of key targets were conducted through Metascape database. Molecular docking between identified components and core targets was conducted by TCMSP and PDB databases. amber18 software package was used to simulate 200 ns molecular dynamics of the docking complexes with the top 3 positions of bonding energy. Results A total of 22 compounds were identified, including salviaflaside, lithospermic acid, genistein, quercetin, and salvianolic acid Y, among which 16 kinds of phenolic acids and 6 kinds of flavonoids were identified. Based on the identified compounds, 502 potential anti-inflammatory targets were identified through network pharmacology. PPI analysis found that TP53, STAT3, JUN, HIF1A, CTNNB1, CASP3, and TNF were the core targets. Enrichment analysis revealed that core targets may play an anti-inflammatory role by regulating signaling pathways such as programmed death receptor 1 (PD-1), interleukin-17 (IL-17), and advanced glycation end-products/AGEs receptor (AGE-RAGE). The results of molecular docking and molecular dynamics simulation showed that the identified components were free to bind to the key targets, and the binding energy of the top 3 molecules and the receptor protein complex had relatively stable conformation, which did not lead to sustained and significant changes in conformation after binding. Conclusion Based on UHPLC-Q-TOF-MS/MS technology and network pharmacology, we can realize the basic excavation and mechanism study of anti-inflammatory substances in the stems and leaves of Prunella vulgaris, which is helpful to the development and utilization of the resources of non medicinal parts of Prunella vulgaris.