Background: Gastric cancer was still one of the commonly diagnosed cancer types and the third-most common cause of cancer-related death in the world. Gentiopicroside, which is extracted from the Gentianella acuta, is commonly used in both traditional treatment and modern clinical care; therefore, its anticancer effects have been attracted more attention. However, the systematic analysis of action mechanism of Gentiopicroside on gastric cancer (GC) has not yet been carried out.
Aim: A network pharmacology-based strategy combined with molecular docking studies and in vitro validation was employed to investigate potential targets and molecular mechanism of Gentiopicroside against GC.
Materials and Methods: Potential targets of Gentiopicroside, as well as related genes of GC, were acquired from public databases. Potential targets, and signaling pathways were determined through bioinformatic analysis, including protein–protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the above findings.
Results: Our findings revealed that the anticancer activity of Gentiopicroside potentially involves 53 putative identified target genes. In addition, GO, KEGG, and network analyses revealed that these targets were associated with cell proliferation, metabolic process, and other physiological processes. Furthermore, we have proved that critical compound affected the expression of CCND1, CCNE1, p-AKT and p-P38 at protein levels. These findings provide an overview of the anticancer action of Gentiopicroside from a network perspective; meanwhile, it might also set an example for future studies of other materials used in traditional Chinese medicine (TCM).
Conclusion: This study comprehensively illuminated the potential targets and molecular mechanism of Gentiopicroside against GC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of TCM treating for disease.



中文翻译：

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基于网络药理学的龙胆苦苷抗胃癌潜在机制研究


背景：胃癌仍然是世界上常见的癌症类型之一，也是癌症相关死亡的第三大常见原因。龙胆苦甙是从急性龙胆中提取的，常用于传统治疗和现代临床护理；因此，其抗癌作用受到越来越多的关注。然而，目前尚未对龙胆苦苷抗胃癌（GC）的作用机制进行系统分析。

目的：采用基于网络药理学的策略，结合分子对接研究和体外验证，研究龙胆苦苷抗GC的潜在靶点和分子机制。

材料和方法：从公共数据库中获取龙胆苦苷的潜在靶标以及GC相关基因。通过生物信息学分析确定潜在靶标和信号通路，包括蛋白质-蛋白质相互作用（PPI）、基因本体论（GO）和京都基因和基因组百科全书（KEGG）。随后进行分子对接和细胞实验进一步验证上述发现。

结果：我们的研究结果表明，龙胆苦苷的抗癌活性可能涉及 53 个假定的已识别靶基因。此外，GO、KEGG和网络分析表明这些靶点与细胞增殖、代谢过程和其他生理过程相关。此外，我们还证明关键化合物在蛋白质水平上影响 CCND1、CCNE1、p-AKT 和 p-P38 的表达。这些发现从网络角度概述了龙胆苦苷的抗癌作用；同时，它也可能为未来其他中药材料的研究提供借鉴。

结论：本研究全面阐明了龙胆苦苷抗GC的潜在靶点和分子机制。这也为揭示中医治疗疾病的科学依据和治疗机制提供了一种有前景的方法。