Background: Jianwei Yuyang Tablet (JWYY), a Chinese herbal formulation, has been approved for the treatment of various gastric diseases in clinic and has demonstrated significant therapeutic effects in patients with multiple types of gastric ulcers (GU).

Purpose: This study aimed to evaluate the protective effects of JWYY on alcohol-induced gastric ulcers in mice and to explore the potential mechanisms underlying its therapeutic effects.

Methods: Gastric ulcers were induced in male C57/BL6J mice through a single oral dose of 10 ml/kg alcohol. The extent of gastric mucosal injury was evaluated using ulcer index (UI) and histopathological examinations. Additionally, the levels of inflammatory biomarkers, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA), were determined using enzyme-linked immunosorbent assay (ELISA). Transcriptomic sequencing (RNA-seq) and network pharmacology were used to explore the potential mechanisms underlying the therapeutic effects of JWYY in the treatment of GU. Changes in potential hub genes and pathways related to the therapeutic effects of JWYY were assessed using western blot, qRT-PCR, and immunofluorescence analyses. The protective effects of potential active ingredients were evaluated in vitro models.

Results: The administration of JWYY significantly decrease the UI and alleviated gastric hemorrhagic necrosis, submucosal edema, and destruction of epithelial cells in mouse model of GU. JWYY markedly suppressed IL-1β, TNF-α and MDA levels, and restored mucosal integrity (ZO-1 expression). RNA-seq revealed dual roles of JWYY, including the inhibition of JAK2-STAT3/NF-κB pathways to attenuate inflammation and the rescue of activation of PI3K-AKT/DNA repair pathways to enhance cell survival. Network pharmacology and UPLC-MS/MS identified quercetin, morin, naringenin, catechin as key bioactive components, which bind to JAK2/PDGFRA, decreased inflammation, reduced oxidative stress, and inhibited apoptosis in vitro.

Conclusions: This study deciphers the multi-target, multi-pathway mechanisms underline the JWYY in the treatment of alcohol-induced GU, integrating TCM principles with modern pharmacology. The identified bioactive components and pathways provide a scientific foundation for clinical usage of JWYY and indicated the important of targeting JAK-STAT/NF-κB signaling in the treatment of GU. These bioactive components not only explain the mechanism of complex TCM formulations but also can be used to improve the therapeutic efficacy.

Keywords: Gastric ulcer; JAK2-STAT3 signaling pathways; Jianwei yuyang tablet; NF-ĸB signaling pathway; Network pharmacology; RNA-seq.

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背景： 健胃愈疡片（JWYY），是一种中药复方制剂，已在临床上被批准用于治疗各种胃病，并在不同类型胃溃疡（GU）患者的治疗中显示出显著的疗效。

目的： 本研究旨在评估JWYY对酒精诱导的小鼠胃溃疡保护作用，并探讨其潜在的治疗机制。

方法： 通过一次口服给小鼠10 ml/kg酒精剂量，诱发雄性C57/BL6J小鼠胃溃疡。使用溃疡指数（UI）和组织病理学检查评估胃黏膜损伤的程度。此外，采用酶联免疫吸附试验（ELISA）测定包括白细胞介素-1β (IL-1β)、肿瘤坏死因子-α (TNF-α) 和丙二醛（MDA）在内的炎症生物标志物的水平。使用转录组测序（RNA-seq）和网络药理学探索JWYY治疗GU潜在机制。采用Western blot、qRT-PCR 和免疫荧光分析评估与JWYY治疗效果相关的潜在核心基因和通路的变化。在体外模型中评价了活性成分的保护作用。

结果： JWYY给药显著降低了UI，缓解了胃出血性坏死、黏膜下水肿及上皮细胞破坏的小鼠GU模型的症状。JWYY明显抑制了IL-1β、TNF-α和MDA水平，并恢复了粘膜完整性（ZO-1表达）。RNA-seq揭示了JWYY的双重作用，包括通过抑制JAK2-STAT3/NF-κB通路减轻炎症并激活PI3K-AKT/DNA修复通路以增强细胞存活。网络药理学和UPLC-MS/MS鉴定出了黄酮、山奈酚、柚皮素、儿茶素作为关键生物活性成分，它们与JAK2/PDGFRA结合，在体外减少了炎症、氧化应激及抑制了凋亡。

结论： 本研究解码了多靶点、多通路机制解释了JWYY在治疗酒精诱导的GU中的作用，将中医原理与现代药理学相结合。已鉴定出的生物活性成分和路径为JWYY临床应用提供了科学基础，并指出针对JAK-STAT/NF-κB信号传导的重要性。这些生物活性成分不仅解释了复杂中药复方的作用机制，还可以用于提高治疗效果。

关键词： 胃溃疡；JAK2-STAT3 信号通路；健胃愈疡片；NF-ĸB 信号通路；网络药理学；RNA-seq。