Pradeep Sushma, Sai Chakith M R, Sindhushree S R, Reddy Pruthvish, Sushmitha Esther, Purohit Madhusudan N, Suresh Divya, Swamy Shivananju Nanjunda, Silina Ekaterina, Manturova Natalia, Stupin Victor, Kollur Shiva Prasad, Shivamallu Chandan, Achar Raghu Ram
Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India.
Centre for Digital Health and AI, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India.
Front Chem. 2025 Mar 12;13:1549186. doi: 10.3389/fchem.2025.1549186. eCollection 2025.
Alzheimer's disease (AD) and glioblastoma (GBM) are complex neurological disorders with distinct pathologies but overlapping molecular mechanisms, including neuroinflammation, oxidative stress, and dysregulated signaling pathways. Despite significant advancements in research, effective therapies targeting both conditions remain elusive. Identifying shared molecular targets and potential therapeutic agents could offer novel treatment strategies for these disorders.
The study employs an integrative network pharmacology approach to explore the therapeutic potential of bioactive compounds from , a medicinal herb known for its neuroprotective and anti-inflammatory properties. A systematic methodology was adopted, starting with network pharmacology analysis using STRING and DisGeNET databases, which identified 617 common genes associated with AD and GBM. Among these, key hub genes-TP53, STAT3, AKT1, and IL6-were prioritized using Cytoscape for network visualization and analysis.
Molecular docking studies were conducted using PyRx software to assess the binding interactions of 26 phytochemicals from Eclipta alba against the identified target genes. Luteolin exhibited the highest binding affinity to IL6 (-7.8 kcal/mol), forming stable hydrogen bonds and hydrophobic interactions. To further validate this interaction, molecular dynamics simulations (MDS) were performed using GROMACS, confirming the stability of the Luteolin-IL6 complex. Additionally, MM-PBSA binding energy calculations using AmberTools (-145.44 kJ/mol) provided further evidence of a strong and stable interaction. Pharmacokinetic and toxicity evaluations, conducted using SwissADME and pkCSM, highlighted luteolin's favorable drug-like properties, including good bioavailability and low toxicity. These findings suggest that luteolin may serve as a promising multi-target therapeutic agent for AD and GBM by modulating key pathological pathways.
The present study provides a strong computational foundation for further and validation. The results highlight the potential of luteolin in developing dual-target treatment strategies for neurodegenerative and oncological disorders, offering new avenues for therapeutic advancements.
阿尔茨海默病（AD）和胶质母细胞瘤（GBM）是复杂的神经系统疾病，具有不同的病理特征，但分子机制存在重叠，包括神经炎症、氧化应激和信号通路失调。尽管研究取得了重大进展，但针对这两种疾病的有效疗法仍然难以捉摸。确定共同的分子靶点和潜在的治疗药物可能为这些疾病提供新的治疗策略。
本研究采用综合网络药理学方法，探索一种以神经保护和抗炎特性闻名的草药——墨旱莲中生物活性化合物的治疗潜力。采用了一种系统的方法，首先使用STRING和DisGeNET数据库进行网络药理学分析，确定了617个与AD和GBM相关的共同基因。其中，关键枢纽基因——TP53、STAT3、AKT1和IL6——使用Cytoscape进行网络可视化和分析时被优先考虑。
使用PyRx软件进行分子对接研究，以评估墨旱莲中26种植物化学物质与已确定的靶基因的结合相互作用。木犀草素对IL6表现出最高的结合亲和力（-7.8千卡/摩尔），形成稳定的氢键和疏水相互作用。为了进一步验证这种相互作用，使用GROMACS进行了分子动力学模拟（MDS），证实了木犀草素-IL6复合物的稳定性。此外，使用AmberTools进行的MM-PBSA结合能计算（-145.44千焦/摩尔）提供了更强且稳定相互作用的进一步证据。使用SwissADME和pkCSM进行的药代动力学和毒性评估突出了木犀草素良好的类药物特性，包括良好的生物利用度和低毒性。这些发现表明，木犀草素可能通过调节关键病理途径，作为一种有前景的AD和GBM多靶点治疗药物。
本研究为进一步的实验和临床验证提供了坚实的计算基础。结果突出了木犀草素在开发神经退行性疾病和肿瘤疾病双靶点治疗策略方面的潜力，为治疗进展提供了新途径。
