目的 研究新疆阿魏叶水提物（Ferula sinkiangensis leaf aqueous extract，FSLAE）抗酒精性胃炎（alcoholic gastritis，AG）的入血活性成分及分子机制，为其药用开发及新疆特色药用植物资源利用提供科学依据。方法 采用超高效液相色谱-四极杆飞行时间质谱技术（ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry，UPLC-Q-TOF/MS）表征FSLAE体外化学成分及大鼠入血成分；通过网络药理学筛选FSLAE入血成分与AG的交集靶点，通过基因本体（gene ontology，GO）及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析预测核心通路，分子对接验证核心成分与靶点的结合活性。以70%乙醇诱导大鼠AG模型，设置对照组、模型组及FSLAE高、中、低剂量（150、100、50 mg/kg）组和铝碳酸镁（31.5 mg/kg）组，每组10只，连续给药7 d。通过苏木素-伊红（hematoxylin-eosin，HE）染色观察胃黏膜病理变化，ELISA检测血清中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-17A（interleukin-17A，IL-17A）和IL-6水平，全自动生化分析仪检测肝胰功能及营养相关指标，Western blotting检测胃组织中Janus激酶2（Janus kinase 2，JAK2）/信号转导和转录激活因子3（signal transducer and activator of transcription 3，STAT3）通路相关蛋白的表达。结果 从FSLAE中共表征出191种体外化学成分，确定23个入血成分，主要为酚酸类、香豆素类、脂肪酸类等，核心活性成分为阿魏酸、异阿魏酸、4-甲基伞形酮等。网络药理学筛选出FSLAE与AG的148个交集靶点，显著富集于TNF、JAK/STAT等炎症相关通路，核心靶点为STAT3、JAK2、TNF等；分子对接验证核心成分与核心靶点结合能均＜-6 kcal/mol，结合活性良好。体内实验结果显示，FSLAE可呈剂量相关性改善AG大鼠胃黏膜病理损伤并缓解体质量增长滞后，显著下调血清中促炎因子（TNF-α、IL-17A、IL-6）及肝胰功能异常指标丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）、淀粉酶（amylase，AMY）、总胆红素（total bilirubin，TB）水平（P＜0.05、0.01、0.001），上调营养相关指标白蛋白（albumin，ALB）、总蛋白（total protein，TP）水平（P＜0.05、0.01），并抑制胃组织JAK2、STAT3的磷酸化水平（P＜0.01、0.001）。结论 FSLAE通过其入血活性成分抑制JAK2/STAT3信号通路过度激活、减轻炎症反应，发挥抗AG的胃黏膜保护作用，酚酸类、香豆素类为其核心药效物质基础。

Objective To study the blood-entry active components and molecular mechanisms of Ferula sinkiangensis leaf aqueous extract (FSLAE) against alcoholic gastritis (AG), so as to provide a scientific basis for its medicinal development and the utilization of characteristic medicinal plant resources in Xinjiang. Methods Ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to characterize the in vitro chemical constituents of FSLAE and the blood-entry constituents of rats. The intersecting targets between blood-entry components of FSLAE and AG were screened by network pharmacology. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were applied to predict the core pathways, and molecular docking was performed to verify the binding activity of core components to key targets. The AG rat model was induced by 70% ethanol, control group, model group, FSLAE high-, medium-, low dose (150, 100, 50 mg/kg) groups and magnesium aluminum carbonate (31.5 mg/kg) group were set up, with 10 rats in each group, drugs were continuously given for 7 d. Pathological changes of gastric mucosa were observed by hematoxylin-eosin (HE) staining. Levels of tumor necrosis factor-α (TNF-α), interleukin-17A (IL-17A) and IL-6 in serum were detected by ELISA. Hepatic and pancreatic function as well as nutrition-related indicators were measured using an automatic biochemical analyzer. The expression of proteins related to the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway in gastric tissue was determined by Western blotting. Results A total of 191 in vitro chemical constituents were identified from FSLAE, among which 23 constituents were confirmed as blood-entry components, mainly including phenolic acids, coumarins, fatty acids, etc. The core active components were ferulic acid, isoferulic acid and 4-methylumbelliferone. Network pharmacology identified 148 intersecting targets between FSLAE and AG, which were significantly enriched in inflammation-related pathways such as TNF and JAK/STAT pathways, with STAT3, JAK2 and TNF as the core targets. Molecular docking verified that the binding energies of core components to core targets were all less than &8722;6 kcal/mol, indicating favorable binding activity. In vivo experiments results showed that FSLAE dose-dependently ameliorated gastric mucosal pathological injury and alleviated the lag in body weight gain in AG rats. FSLAE significantly downregulated levels of pro-inflammatory factors (TNF-α, IL-17A, IL-6) and abnormal hepatic and pancreatic function markers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase (AMY) and total bilirubin (TB) in serum (P < 0.05, 0.01, 0.001), upregulated levels of nutrition-related indicators such as albumin (ALB) and total protein (TP) (P < 0.05, 0.01), inhibited the phosphorylation levels of JAK2 and STAT3 in gastric tissue (P < 0.01, 0.001). Conclusion FSLAE exerts a gastroprotective effect against AG by inhibiting the excessive activation of JAK2/STAT3 signaling pathway and alleviating inflammatory responses via its blood-entry active components. Phenolic acids and coumarins serve as the core pharmacodynamic material basis.

R285.5

“天山英才”医药卫生高层次人才培养计划（TSYC202401A081）；国家自然科学基金资助项目（82560824）；新疆医科大学自然科学青年研究项目（XJ2025007502）