Systems analysis of Berberis vulgaris alkaloids unveils their functional synergy and drug-like potential

IF 3.1 4区生物学 Q2 BIOLOGY

Computational Biology and Chemistry Pub Date : 2025-09-26 DOI:10.1016/j.compbiolchem.2025.108698

Chinenyenwa Fortune Chukwuneme , Samantha Gildenhuys

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引用次数: 0

Abstract

Berberis species are rich in isoquinoline alkaloids with promising therapeutic properties for various diseases, including SARS-CoV-2. Despite their known medicinal attributes, the potential for combining them at suitable doses remains underexplored. This study investigated the compound–target interactions, functional enrichment, and pharmacokinetic profiles of seven B. vulgaris alkaloids (berberine, palmatine, berberrubine, lambertine, obamegine, berbidine, and berbamine) using an in-silico approach. Compound–target interactions were identified using SwissTargetPrediction. Protein-protein interaction (PPI) networks were constructed using STRING in Cytoscape, and an UpSet plot was generated in Python to visualize overlapping targets and potential synergy. Functional enrichment analysis was performed in DAVID using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, followed by compound-gene-pathway network construction in Cytoscape. Pharmacokinetic profiles of compounds were assessed using ADMET-AI. A total of 42 genes were shared by at least two compounds. Genes associated with neurotransmission (DRD, ADRA, and ADRB) were identified as hubs mediating key functional interactions. Berbamine and obamegine shared the highest number of targets (10). Functional enrichment by KEGG and GO identified 16 and 20 significantly enriched pathways and biological processes, respectively, and formed networks consisting of distinct nodes (pathway = 67, GOBP = 69) and edges (pathway = 228, GOBP = 229). Favorable drug-likeness was identified for all alkaloids, excluding berbamine and obamegine (0.3), and low clinical toxicity (0.0–0.3). The results highlight the therapeutic potential of B. vulgaris alkaloids to provide complementary and synergistic effects across different disease pathways and support their development in botanical medicine.

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小檗生物碱的系统分析揭示了它们的功能协同作用和药物潜力。

小檗属植物富含异喹啉生物碱，对包括SARS-CoV-2在内的多种疾病具有良好的治疗作用。尽管它们具有已知的药用特性，但以适当剂量组合它们的潜力仍未得到充分探索。本研究利用芯片技术研究了7种寻常草生物碱（小檗碱、棕榈碱、小檗碱、兰伯碱、奥巴马碱、小檗碱和小檗碱）的化合物-靶标相互作用、功能富集和药代动力学特征。使用SwissTargetPrediction识别化合物靶标相互作用。在Cytoscape中使用STRING构建蛋白-蛋白相互作用（PPI）网络，并在Python中生成一个心烦图来可视化重叠的靶点和潜在的协同作用。利用Gene Ontology和京都基因与基因组百科全书（KEGG）途径在DAVID中进行功能富集分析，然后在Cytoscape中构建化合物-基因-途径网络。使用ADMET-AI评估化合物的药代动力学特征。至少两种化合物共有42个基因。与神经传递相关的基因（DRD、ADRA和ADRB）被确定为介导关键功能相互作用的枢纽。bamine和obamegine的目标数量最多（10个）。KEGG和GO功能富集分别鉴定出16条和20条显著富集的通路和生物过程，并形成由不同节点（通路= 67,GOBP = 69）和边缘（通路= 228,GOBP = 229）组成的网络。除小檗碱和奥巴马碱（0.3）外，所有生物碱均具有良好的药物相似性，临床毒性较低（0.0-0.3）。研究结果表明，寻常草生物碱在不同疾病途径中具有互补和协同作用的治疗潜力，并支持其在植物医学中的发展。

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来源期刊

Computational Biology and Chemistry 生物-计算机：跨学科应用

CiteScore

6.10

自引率

3.20%

发文量

142

审稿时长

24 days

期刊介绍： Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered. Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered. Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.