背景神经生长因子(NGF)是口腔癌疼痛治疗的新靶点。它在慢性疼痛的伤害性感受中起主要作用。手术,连同化疗或放疗,是治疗病人的黄金标准,但副作用也很明显。使用天然植物化学物质进行新的有效干预可以提高患者的依从性并提高口腔癌患者的生活质量。文献检索显示NGF与口腔癌疼痛呈正相关。Nigellasativa(N.sativa)和cuscutareflexa(C.reflexa)已证明具有抗癌作用,但它们与NGF的活性尚未被探索。目的和目的我们旨在鉴定紫花苜蓿和紫花苜蓿中潜在的植物化学物质。我们还检查了植物化学物质的NGF阻断活性。分子对接和分子动力学(MD)模拟评估了NGF蛋白与所选植物化学配体之间的结合能和稳定性。材料和方法我们从UniProt获得了蛋白质NGF结构(ID:4EDX,P01138,β-神经生长因子),使用PubChemID:10281的配体(百里香醌)结构和使用PubChemID:66065的配体(cuscutin)结构。Maestro蛋白(薛定谔公司,曼海姆,德国)用于分子对接。德斯蒙德模拟包(薛定谔公司,曼海姆,德国)用于模拟100纳秒(ns)的MD。我们已经通过均方根偏差(RMSD)值评估了蛋白质和配体之间的相互作用。结果评估了百里香醌和cuscutin与NGF的相互作用。在与百里香醌相互作用时,从0.6埃到2.5埃到80ns有轻微的波动,最后到4.8埃到100ns。在与cuscutin互动时,从0.8埃到4.8埃到90ns出现了轻微的波动,并在6.4埃到100ns结束。我们发现我们的药物组合与NGF受体之间存在稳定的相互作用。结论我们已经确定了百里香醌之间的稳定相互作用,cuscutin,和NGF通过我们的MD模拟。因此,它可以用作缓解疼痛和控制肿瘤进展的NGF抑制剂。对这种新型药物与植物化学物质组合的进一步体外和体内评估将有助于我们了解其生物活性和在口腔癌治疗中的潜在临床应用。
Background Nerve growth factor (NGF) is a novel target of pain therapeutics for oral cancer, and it plays a main role in the nociception of chronic pain. Surgery, along with chemotherapy or radiotherapy, is the gold standard for treating patients, but the side effects are significant as well. Newer effective interventions with natural phytochemicals could improve patient compliance and enhance the quality of life among patients with oral cancer. A literature search revealed a positive correlation between NGF and oral cancer pain. Nigella sativa (N. sativa) and Cuscuta reflexa (C. reflexa) have proven anticancer effects, but their activity with NGF is unexplored. Aims and objectives We aimed to identify the potential phytochemicals in N. sativa and C. reflexa. We also checked the NGF-blocking activity of the phytochemicals. Molecular docking and molecular dynamic (MD) simulations evaluated the binding energy and stability between the NGF protein and selected phytochemical ligands. Materials and methods We obtained protein NGF structure from UniProt (ID: 4EDX, P01138, Beta-nerve growth factor), ligand (
thymoquinone) structure using PubChem ID: 10281, and ligand (cuscutin) structure using PubChem ID: 66065. Maestro protein (Schrödinger Inc., Mannheim, Germany) was used for molecular docking. Desmond Simulation Package (Schrödinger Inc., Mannheim, Germany) was used to model MD for 100 nanoseconds (ns). We have assessed the interaction between the protein and ligands by root mean square deviation (RMSD) values. Results The interaction of
thymoquinone and cuscutin with NGF was assessed. While interacting with
thymoquinone, there was mild fluctuation from 0.6 Å to 2.5 Å up to 80 ns and ended up at 4.8 Å up to 100 ns. While interacting with cuscutin, mild fluctuation was seen from 0.8 Å to 4.8 Å till 90 ns and ended at 6.4 Å up to 100 ns. We found a stable interaction between our drug combination and the NGF receptor. Conclusion We have identified a stable interaction between
thymoquinone, cuscutin, and NGF by our MD simulations. Hence, it could be used as an NGF inhibitor for pain relief and to control tumor progression. Further in vitro and in vivo evaluations of this novel drug combination with phytochemicals will help us understand their biological activities and potential clinical applications in oral cancer therapeutics.