Abstract：
Spinal cord injury (SCI) is a severe traumatic condition in spinal surgery characterized by nerve damage in and below the injured area. Despite advancements in understanding the pathophysiology of SCI, effective clinical treatments remain elusive. Selenium compounds have become a research hotspot due to their diverse medicinal activities. Previously, our group synthesized a selenium-containing Compound 34# with significant anti-inflammatory activity. This study aimed to explore the anti-SCI effects of selenium-containing compounds using network pharmacology, molecular docking (MD), and ADMET methods. To identify SCI-related targets and those associated with 34#, GeneCards, NCBI, and SEA databases were employed. Eight overlapping targets were considered candidate targets, and molecular docking was performed using the PDB database and AutoDock software. The STRING database was used to obtain protein-protein interactions (PPI). Molecular dynamics simulation, MM/GBSA binding free energy score, and ADMET prediction were used to evaluate the potential targets and drug properties of 34#. Finally, experiments on NSC34 cells and mice were to verify the effects of 34# on SCI. Our results revealed eight candidate targets for 34# in the treatment of SCI. PPI and MD identified ADRB2 and HTR1F as the highest connectivity with 34#. ADMET analysis confirmed the low toxicity and safety of 34#. In vitro and in vivo models validated the anti-SCI effects. Our study elucidated candidate targets for alleviating SCI with 34#, explored PPI and target-related signaling pathways, and validated its anti-SCI effects. These findings enhance our understanding of 34#\'s mechanism in treating SCI, positioning it as a potential candidate for SCI prevention.
摘要：
脊髓损伤（SCI）是脊柱手术中的严重创伤性疾病，其特征是受伤区域及其下方的神经损伤。尽管在理解SCI的病理生理学方面取得了进展，但有效的临床治疗仍然难以捉摸。硒化合物因其具有多样化的药用活性而成为研究热点。以前,我们小组合成了具有显著抗炎活性的含硒化合物34#。本研究旨在通过网络药理学探讨含硒化合物的抗SCI作用,分子对接（MD），和ADMET方法。为了识别SCI相关目标和与34#相关的目标，GeneCards,NCBI,并采用了SEA数据库。八个重叠目标被视为候选目标，使用PDB数据库和AutoDock软件进行分子对接。STRING数据库用于获得蛋白质-蛋白质相互作用(PPI)。分子动力学模拟,MM/GBSA结合自由能评分，和ADMET预测用于评估34#的潜在靶标和药物性质。最后,在NSC34细胞和小鼠实验中验证34#对SCI的影响。我们的结果揭示了SCI治疗中34#的八个候选目标。PPI和MD将ADRB2和HTR1F确定为34#的最高连通性。ADMET剖析证实了34#的低毒性和平安性。体外和体内模型验证了抗SCI作用。我们的研究阐明了34#减轻SCI的候选目标，探索PPI和靶标相关信号通路，并验证了其抗SCI效果。这些发现增强了我们对34#SCI治疗机制的理解，将其定位为SCI预防的潜在候选者。
