Chintaluri Pratham Gour, Ganapathy Vilasam Sreekala Aparna, Gupta Krishna Kant, Sivadasan Aparna, Nathan Vinod Kumar
School of Chemical and Biotechnology, SASTRA Deemed to be University, Thirumalasamudram, Thanjavur, India.
National Centre for Cell Science, NCCS Complex, University of Pune Campus, Pune, India.
J Biomol Struct Dyn. 2025 Mar 4:1-16. doi: 10.1080/07391102.2025.2472403.
L. is immensely valuable in pharmacology. Computational approach through network pharmacology has been attempted to understand lead molecules of Cressa and their interactions with multiple targets. The phytochemical components of methanolic extracts of Cressa leaves were identified using GC-MS analysis, revealing 16 compounds. Using the identified lead molecules, target proteins were predicted using SWISS-target prediction and were analyzed using Cytoscape. This led to the identification of 56 candidate protein targets, which were used to construct a network using CytoHubba, Centiscape, MCODE, and KEGG pathways. The STRING network was created using Cytoscape for analyzing protein-protein interactions, and the top 5 genes were chosen from a total of 12 algorithms in CytoHubba. The antioxidant effects of were investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, which showed an increase in the trend activity of the plant extract with an inhibition percentage of 51.53 ± 0.003%. This was further validated by ferric reducing antioxidant power (FRAP) assay that resulted in an antioxidant activity of 6.64 µg/mL at a high concentration of 500 µg/mL. Molecular docking and simulation were performed to study the interaction of human cyclooxygenase-2 (PDB ID: 5KIR) with Cressa metabolites. 5KIR exhibited a higher interaction with methyl stearate, forming two H-bond interactions with Arg 120 and Tyr 355. Molecular dynamics simulation analysis confirmed the stability of the protein-ligand complex. The network pharmacology analysis of putative proteins obtained from revealed that the peroxisome proliferator-activated receptor gamma (PPARG) gene is found in numerous cancer pathways and can be inhibited.
刺蕊草在药理学中具有巨大价值。人们已尝试通过网络药理学的计算方法来了解刺蕊草的先导分子及其与多个靶点的相互作用。采用气相色谱 - 质谱联用（GC - MS）分析鉴定了刺蕊草叶片甲醇提取物的植物化学成分，共鉴定出16种化合物。利用鉴定出的先导分子，通过SWISS - target预测来预测靶蛋白，并使用Cytoscape进行分析。这导致鉴定出56个候选蛋白靶点，这些靶点被用于使用CytoHubba、Centiscape、MCODE和KEGG通路构建网络。使用Cytoscape创建STRING网络以分析蛋白质 - 蛋白质相互作用，并从CytoHubba的总共12种算法中选择了前5个基因。使用2,2 - 二苯基 - 1 - 苦基肼（DPPH）自由基清除活性研究了刺蕊草的抗氧化作用，结果显示植物提取物的活性呈上升趋势，抑制率为51.53±0.003%。通过铁离子还原抗氧化能力（FRAP）测定进一步验证了这一结果，在500μg/mL的高浓度下，抗氧化活性为6.64μg/mL。进行了分子对接和模拟，以研究人环氧化酶 - 2（PDB ID：5KIR）与刺蕊草代谢物的相互作用。5KIR与硬脂酸甲酯表现出更高的相互作用，与Arg 120和Tyr 355形成两个氢键相互作用。分子动力学模拟分析证实了蛋白质 - 配体复合物的稳定性。对从刺蕊草中获得的假定蛋白质进行的网络药理学分析表明，过氧化物酶体增殖物激活受体γ（PPARG）基因存在于众多癌症通路中且可被抑制。
