Zheng Jia, Jiao Zhiyong, Yang Xinyu, Ruan Qing, Huang Yuzhe, Jin Cheng, Gui Shuangying, Xuan Zihua, Jia Xiaoyi
School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
Anhui Province Key Laboratory of Bioactive Natural Products, Hefei 230012, China.
Biol Pharm Bull. 2025;48(6):849-859. doi: 10.1248/bpb.b24-00882.
Wenweishu (WWS), a traditional gastritis formula, was studied to elucidate its mechanisms in preventing water immersion restraint stress-induced gastric ulcers (GU) in rats. The degree of gastric tissue damage was assessed in experimental rats based on the gastric mucosal ulcer index and pathological observation. The antioxidant properties of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) were detected in gastric tissues, along with expression levels of inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. The core components, primary targets, and putative mechanisms of WWS were predicted using network pharmacology and molecular docking and validated via immunohistochemistry and immunoblotting analyses. WWS reduced the ulcer index, increased SOD and GSH-px, and decreased IL-1β, IL-6, TNF-α, and MDA levels. A total of 126 WWS components were identified and associated with 4920 GU-associated targets via network pharmacological analysis. Data from Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed associations of the core targets with multiple pathways, in particular, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling. Molecular docking analysis confirmed significant docking activity of the main bioactive components with the core targets tumor protein (TP53) and protein kinase Bα (AKT1). Immunohistochemistry and Western blot analyses showed that WWS markedly suppressed phosphorylation levels of Akt and PI3K proteins in gastric tissues. WWS exerts a protective effect on the gastric mucosa by inhibiting the PI3K/Akt pathway, attenuating inflammatory factors and oxidative damage. The collective findings provide a scientific basis for the application of WWS in the management of GU.
温胃舒（WWS）是一种传统的胃炎配方，本研究旨在阐明其预防大鼠水浸束缚应激诱导的胃溃疡（GU）的机制。基于胃黏膜溃疡指数和病理观察对实验大鼠的胃组织损伤程度进行评估。检测胃组织中丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-px）的抗氧化特性，以及肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β和IL-6等炎症因子的表达水平。使用网络药理学和分子对接预测WWS的核心成分、主要靶点和潜在机制，并通过免疫组织化学和免疫印迹分析进行验证。WWS降低了溃疡指数，提高了SOD和GSH-px水平，并降低了IL-1β、IL-6、TNF-α和MDA水平。通过网络药理学分析共鉴定出126种WWS成分，并与4920个GU相关靶点相关联。京都基因与基因组百科全书（KEGG）分析数据显示核心靶点与多种途径相关，特别是磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路。分子对接分析证实主要生物活性成分与核心靶点肿瘤蛋白（TP53）和蛋白激酶Bα（AKT1）具有显著的对接活性。免疫组织化学和蛋白质印迹分析表明，WWS显著抑制胃组织中Akt和PI3K蛋白的磷酸化水平。WWS通过抑制PI3K/Akt途径、减轻炎症因子和氧化损伤对胃黏膜发挥保护作用。这些研究结果为WWS在GU治疗中的应用提供了科学依据。
