目的 探讨四磨汤在脓毒症治疗中的潜在机制，并通过动物实验、网络药理学和分子对接技术揭示其活性成分及作用靶点。方法 50只小鼠随机分为5组：四磨汤高、中、低剂量（12.00、7.56、3.00 mL·kg⁻¹）组、模型组以及对照组，除对照组外，采用ip注射25 mg·kg⁻¹脂多糖制作BALB/c小鼠脓毒症模型。记录造模后24 h各组小鼠死亡率以及检测血清中白细胞介素-1β（IL-1β）、IL-6、肿瘤坏死因子-α（TNF-α）水平。利用中药系统药理学数据库与分析平台（TCMSP）筛选四磨汤的活性成分，并通过PubChem数据库获取其小分子结构。采用SwissTargetPrediction预测潜在靶点，利用GeneCards和CTD数据库筛选脓毒症相关靶点。通过R语言“VennDiagram”包分析四磨汤靶点与脓毒症靶点的交集，并进行基因本体（GO）注释及京都基因与基因组百科全书（KEGG）通路富集分析。采用STRING数据库和Cytoscape3.10.2软件确定核心靶点，利用AutoDock4.2.6软件进行分子对接分析。结果 造模后24 h，四磨汤治疗后明显降低脓毒症小鼠的死亡率，以及明显抑制炎症因子的表达，差异具有统计学意义（P＜0.05）。筛选出四磨汤中的26个活性成分，识别出737个靶点，与脓毒症相关的3 240个靶点交集得到325个潜在靶点。GO和KEGG分析显示，四磨汤的靶点主要涉及炎症反应、免疫调节和组织修复通路。其重要活性成分为lappadilactone，核心靶点包括丝氨酸和苏氨酸激酶1（AKT1）、非受体酪氨酸蛋白激酶（SRC）和表皮生长因子受体（EGFR），分子对接结果表明lappadilactone与这些靶点具有良好的结合能力，结合能分别−29.33、−24.73、−17.36 kJ·mol⁻¹。动物实验显示四磨汤可以降低脓毒症小鼠血清中AKT1水平，差异具有统计学意义（P＜0.05）。结论 四磨汤通过调节AKT1、SRC和EGFR等核心靶点，可能对脓毒症产生治疗作用。

Objective To investigate the potential mechanisms of Simo Decoction in the treatment of sepsis and elucidate its active components and therapeutic targets through animal experiments, network pharmacology, and molecular docking techniques. Methods A sepsis model was established in BALB/c mice by ip injection of lipopolysaccharide (25 mg·kg⁻¹). Fifty mice were randomly divided into five groups: Simo Decoction high-, middle-, low-dose (12.00, 7.56, 3.00 mL·kg⁻¹) groups, model group, and control group. Mortality rates were recorded 24 h after modeling, and serum levels of IL-1β, IL-6, and TNF-α were measured. Active components of Simo Decoction were identified using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and their molecular structures were retrieved from the PubChem database. Potential targets were predicted using SwissTargetPrediction, and sepsis-related targets were identified through the GeneCards and Comparative Toxicogenomics Database (CTD). The intersection of Simo Decoction targets and sepsis targets was analyzed using the "VennDiagram" package in R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Core targets were identified through the STRING database and Cytoscape 3.10.2 software. Molecular docking analyses were performed using AutoDock 4.2.6. Results At 24 h post-modeling, Simo Decoction treatment significantly reduced mortality and inhibited the expression of inflammatory cytokines in septic mice, with statistically significant differences (P < 0.05). Twenty-six active components of Simo Decoction were identified, yielding 737 potential targets. The intersection with 3 240 sepsis-related targets resulted in 325 common targets. GO and KEGG analyses revealed that Simo Decoction primarily targets pathways associated with inflammation, immune regulation, and tissue repair. The key active component, lappadilactone, was found to interact with core targets AKT1, SRC, and EGFR. Molecular docking demonstrated favorable binding energies of lappadilactone with these targets, at −29.33, −24.73, −17.36 kJ·mol⁻¹, respectively. Animal experiments demonstrated that Simo Decoction significantly reduced serum AKT1 levels in septic mice, with the difference being statistically significant (P < 0.05). Conclusion Simo Decoction may exert therapeutic effects on sepsis by targeting key molecules such as AKT1, SRC, and EGFR. These findings provide theoretical support for the application of Simo Decoction in sepsis treatment, although further studies are required to verify its clinical efficacy and safety.

R285.5