Wang Meng, Xu Zeyu, Wang Ziyang, Xu Xiaowan, Sun Yongning
Department of Traditional Chinese Medicine Oncology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China.
Traditional Chinese Medicine Oncology Teaching and Research Office, Department of Traditional Chinese Medicine, Naval Medical University, Shanghai, China.
Transl Cancer Res. 2024 Sep 30;13(9):4593-4607. doi: 10.21037/tcr-24-668. Epub 2024 Sep 27.
Although the therapeutic effects of berberine have received some attention in recent years, its potential mechanisms underlying its action against stomach carcinoma (SC) remain unclear. In this study, we aimed to elucidate the mechanisms underlying the effects of berberine against SC using a network pharmacology and experimental verification approach.
Several publicly available databases were used to collect the targets of berberine and SC. Protein-protein interaction (PPI) network, enrichment analyses and molecular docking were performed based on the potential targets of berberine against SC. The potential clinical significance and prognostic value of the targets were predicted by using nomogram and receiver operating characteristic (ROC) analyses. Then the viability and apoptosis of SC cells treated with berberine were determined. Moreover, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) measurements and western blot assay were carried out to validate the predicted mechanisms.
Seventy-six potential targets of berberine against SC were identified. The construction of PPI network enabled the identification of hub targets, such as AKT1, TP53, IL6, JUN and MAPK1. Enrichment analyses showed that berberine was involved in apoptosis, mitophagy, ROS metabolic process, AMPK and MAPK signaling pathway. The expression levels of hub targets also contributed to the clinical prognosis of patients with SC. Molecular docking revealed the possible patterns of direct interaction between berberine and target proteins, including AMPK, TP53 and MAPK1. Experimental results showed that berberine reduced SC cell viability, promoted apoptosis and ROS generation, and contributed to reductions in MMP and ATP levels. Western blot assay demonstrated that berberine increased AMPK and TP53 expression, while decreased phosphorylated-MAPK3/1 expression.
We elucidated the potential action mechanisms of berberine against SC using a network pharmacology approach. Some predicted mechanisms underlying the anti-SC effects were verified based on experimental approaches. Our findings provide a meaningful foundation for berberine as a cellular apoptosis-inducing and energy metabolism-regulating agent against SC. However, experiments and clinical studies need to be further carried out. Moreover, it is necessary to study the potential negative effects of berberine thoroughly.
尽管黄连素的治疗作用近年来受到了一定关注，但其抗胃癌（SC）作用的潜在机制仍不清楚。在本研究中，我们旨在采用网络药理学和实验验证方法阐明黄连素抗SC作用的机制。
使用几个公开可用的数据库收集黄连素和SC的靶点。基于黄连素抗SC的潜在靶点进行蛋白质-蛋白质相互作用（PPI）网络、富集分析和分子对接。通过列线图和受试者工作特征（ROC）分析预测靶点的潜在临床意义和预后价值。然后测定黄连素处理的SC细胞的活力和凋亡情况。此外，进行活性氧（ROS）、线粒体膜电位（MMP）和三磷酸腺苷（ATP）测量以及蛋白质免疫印迹分析以验证预测的机制。
确定了76个黄连素抗SC的潜在靶点。PPI网络的构建使得能够识别枢纽靶点，如AKT1、TP53、IL6、JUN和MAPK1。富集分析表明黄连素参与凋亡、线粒体自噬、ROS代谢过程、AMPK和MAPK信号通路。枢纽靶点的表达水平也对SC患者的临床预后有影响。分子对接揭示了黄连素与靶蛋白之间直接相互作用的可能模式，包括AMPK、TP53和MAPK1。实验结果表明黄连素降低了SC细胞活力，促进了凋亡和ROS生成，并导致MMP和ATP水平降低。蛋白质免疫印迹分析表明黄连素增加了AMPK和TP53表达，同时降低了磷酸化-MAPK3/1表达。
我们采用网络药理学方法阐明了黄连素抗SC作用的潜在机制。基于实验方法验证了一些抗SC作用的预测机制。我们的研究结果为黄连素作为一种诱导细胞凋亡和调节能量代谢的抗SC药物提供了有意义的基础。然而，需要进一步开展实验和临床研究。此外，有必要深入研究黄连素的潜在负面影响。
