Li Chao, Wen Rou, Liu DeWen, Yan LiPing, Gong Qianfeng, Yu Huan
School of Pharmacy, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, China.
Front Pharmacol. 2022 Jul 12;13:810344. doi: 10.3389/fphar.2022.810344. eCollection 2022.
Gastric ulcer (GU) is one of the most commonly diagnosed diseases worldwide, threatening human health and seriously affecting quality of life. Reports have shown that the Chinese herbal medicine (Thunb.) Nakai (SGN) can treat GU. However, its pharmacological effects deserve further validation; in addition, its mechanism of action is unclear. An acute gastric ulcer (AGU) rat model induced by alcohol was used to evaluate the gastroprotective effect of SGN by analysis of the histopathological changes in stomach tissue and related cytokine levels; the potential mechanisms of action of SGN were investigated via serum metabolomics and network pharmacology. Differential metabolites of rat serum were identified by metabolomics and the metabolic pathways of the identified metabolites were enriched via MetaboAnalyst. Furthermore, the critical ingredients and candidate targets of SGN anti-AGU were elucidated. A compound-reaction-enzyme-gene network was established using Cytoscape version 3.8.2 based on integrated analysis of metabolomics and network pharmacology. Finally, molecular docking was applied to verify the acquired key targets. The results showed that SGN exerted a certain gastroprotective effect via multiple pathways and targets. The effects of SGN were mainly caused by the key active ingredients isofraxidin, rosmarinic, and caffeic acid, which regulate hub targets, such as PTGS2, MAPK1, and KDR, which maintain the homeostasis of related metabolites. Signal pathways involved energy metabolism as well as immune and amino acid metabolism. Overall, the multi-omics techniques were proven to be promising tools in illuminating the mechanism of action of SGN in protecting against diseases. This integrated strategy provides a basis for further research and clinical application of SGN.
胃溃疡（GU）是全球最常见的诊断疾病之一，威胁人类健康并严重影响生活质量。报告显示，中药材石蒜（SGN）可治疗GU。然而，其药理作用值得进一步验证；此外，其作用机制尚不清楚。采用酒精诱导的急性胃溃疡（AGU）大鼠模型，通过分析胃组织的组织病理学变化和相关细胞因子水平来评估SGN的胃保护作用；通过血清代谢组学和网络药理学研究SGN的潜在作用机制。通过代谢组学鉴定大鼠血清中的差异代谢物，并通过MetaboAnalyst对鉴定出的代谢物的代谢途径进行富集。此外，阐明了SGN抗AGU的关键成分和候选靶点。基于代谢组学和网络药理学的综合分析，使用Cytoscape 3.8.2版建立了化合物-反应-酶-基因网络。最后，应用分子对接来验证获得的关键靶点。结果表明，SGN通过多种途径和靶点发挥一定的胃保护作用。SGN的作用主要由关键活性成分异嗪皮啶、迷迭香酸和咖啡酸引起，它们调节枢纽靶点，如PTGS2、MAPK1和KDR，维持相关代谢物的稳态。信号通路涉及能量代谢以及免疫和氨基酸代谢。总体而言，多组学技术被证明是阐明SGN预防疾病作用机制的有前途的工具。这种综合策略为SGN的进一步研究和临床应用提供了依据。
