Tusar Md Touki Tahamid, Munna Md Masudur Rahman, Ahmed Md Hossain, Rahman Md Mostafizur, Fatema Kaniz, Islam Khandakar Mydul, Ali Md Sarafat
Department of Biotechnology and Genetic Engineering, Gopalganj Science and Technology University, Gopalganj, 8100, Bangladesh.
Research Assistant, Dawn of Bioinformatics Limited, Dhaka, 1361, Bangladesh.
Cell Biochem Biophys. 2025 Jun 4. doi: 10.1007/s12013-025-01791-6.
Parkinson's disease (PD), a prevalent, debilitating neurodegenerative disorder, severely impacts patient well-being and imposes a significant societal burden. Current therapies, such as L-DOPA, MAO-B inhibitors, dopamine agonists, and anticholinergics, offer only temporary symptomatic relief and fail to modify disease progression, underscoring the need for safer, more effective treatment strategies. This study aims to evaluate the neuroprotective potential of nine medicinal plants, which have established anti-parkinsonian effects in preclinical models. To achieve this, a network pharmacology approach was used on an in-house database of 1221 constituents to uncover their potential therapeutic mechanisms in PD. The analysis identified 45 constituents interacting with 60 PD targets, including key compounds such as anethole, carvacrol, carnosol, nicotine, and paeonol, which modulate multiple PD-associated genes. Moreover, enrichment analyses conducted utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases revealed significant pathway and biological process enrichment, indicating a possible synergistic interaction among these constituents. In particular, these analyses highlighted that the constituents might influence critical pathways, including the hypoxia-inducible factor-1 signaling pathway, the tumor necrosis factor signaling pathway, and neurodegeneration-related pathways across multiple diseases. Protein-protein interaction analysis identified caspase-3 (CASP3), prostaglandin-endoperoxide synthase-2 (PTGS2/COX2), interleukin-10 (IL-10), and matrix metallopeptidase-9 (MMP9) as hub genes, which are involved in key processes like apoptosis, oxidative stress, autophagy, and neuroinflammation. Additionally, molecular docking, dynamics simulations, and binding free energy calculations demonstrated stable interactions between these constituents and hub targets, indicating their potential to modulate PD pathogenesis. In conclusion, these findings suggest potential therapeutic mechanisms of the identified constituents in PD and may provide a basis for future preclinical and clinical studies to further explore their neuroprotective effects.
帕金森病（PD）是一种常见的、使人衰弱的神经退行性疾病，严重影响患者的健康，并给社会带来巨大负担。目前的治疗方法，如左旋多巴、单胺氧化酶B抑制剂、多巴胺激动剂和抗胆碱能药物，只能提供暂时的症状缓解，无法改变疾病的进展，这凸显了对更安全、更有效治疗策略的需求。本研究旨在评估九种药用植物的神经保护潜力，这些植物在临床前模型中已显示出抗帕金森病的作用。为此，我们采用网络药理学方法，对一个包含1221种成分的内部数据库进行分析，以揭示它们在帕金森病中的潜在治疗机制。分析确定了45种成分与60个帕金森病靶点相互作用，包括茴香脑、香芹酚、鼠尾草酚、尼古丁和丹皮酚等关键化合物，它们可调节多个与帕金森病相关的基因。此外，利用京都基因与基因组百科全书（KEGG）和基因本体论（GO）数据库进行的富集分析显示，存在显著的通路和生物学过程富集，表明这些成分之间可能存在协同相互作用。特别是，这些分析突出表明，这些成分可能影响关键通路，包括缺氧诱导因子-1信号通路、肿瘤坏死因子信号通路以及多种疾病中的神经退行性相关通路。蛋白质-蛋白质相互作用分析确定半胱天冬酶-3（CASP3）、前列腺素内过氧化物合酶-2（PTGS2/COX2）、白细胞介素-10（IL-10）和基质金属蛋白酶-9（MMP9）为枢纽基因，它们参与凋亡、氧化应激、自噬和神经炎症等关键过程。此外，分子对接、动力学模拟和结合自由能计算表明，这些成分与枢纽靶点之间存在稳定的相互作用，表明它们具有调节帕金森病发病机制的潜力。总之，这些发现揭示了所确定成分在帕金森病中的潜在治疗机制，并可能为未来的临床前和临床研究提供基础，以进一步探索它们的神经保护作用。
