ArticleTranslational cancer research2024
Analysis of the mechanism of berberine against stomach carcinoma based on network pharmacology and experimental validation.
Article in Translational cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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5 authors.
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Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: 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,
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