Fu Xuanhao, Ma Boyuan, Zhou Mengmeng, Cheng Yuelin, Liu Linyan, Kan Shunli, Liu Chengjiang, Zhao Xinyan, Feng Sa, Zhu Haoqiang, Hu Wei, Jiang Zehua, Zhu Rusen
Department of Spine Surgery, Tianjin Union Medical Center, Tianjin, China.
Front Mol Neurosci. 2023 Jan 30;16:1074703. doi: 10.3389/fnmol.2023.1074703. eCollection 2023.
Epimedium (EPI) is a common Chinese herb with neuroprotective effects against a variety of central nervous system disorders, especially spinal cord injury (SCI). In this study, we performed network pharmacology and molecular docking analyses to reveal the mechanism underlying EPI treatment of SCI, then validated its efficacy using animal models.
The active ingredients and targets of EPI were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and their targets annotated on the UniProt platform. SCI-related targets were searched from OMIM, TTD, and GeneCards databases. We employed the STRING platform to construct a protein-protein interaction (PPI) network then visualized the results using Cytoscape (3.8.2) software. We also subjected key EPI targets to ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, then docked the main active ingredients with the key targets. Finally, we established an SCI rat model to evaluate efficacy of EPI in treating SCI and validate the effects of different biofunctional modules predicted by network pharmacology.
A total of 133 EPI targets were associated with SCI. GO terms and KEGG pathway enrichment results showed that EPI's effect in treating SCI was significantly associated with inflammatory response, oxidative stress and the PI3K/AKT signaling pathway. Molecular docking results indicated that EPI's active ingredients have a high affinity for the key targets. Results from animal experiments revealed that EPI not only markedly improved Basso, Beattie, and Bresnahan scores in SCI rats, but also significantly improved p-PI3K/PI3K and p-AKT/AKT ratio. Moreover, EPI treatment not only mediated a significant decrease in malondialdehyde (MDA) but also increased both superoxide dismutase (SOD), and glutathione (GSH). However, this phenomenon was successfully reversed by LY294002, a PI3K inhibitor.
EPI improves behavioral performance in SCI rats through anti-oxidative stress, which may be mediated by activation of the PI3K/AKT signaling pathway.
淫羊藿是一种常见的中草药，对多种中枢神经系统疾病具有神经保护作用，尤其是对脊髓损伤（SCI）。在本研究中，我们进行了网络药理学和分子对接分析，以揭示淫羊藿治疗SCI的潜在机制，然后使用动物模型验证其疗效。
通过中药系统药理学（TCMSP）筛选淫羊藿的活性成分和靶点，并在UniProt平台上对其靶点进行注释。从OMIM、TTD和GeneCards数据库中搜索与SCI相关的靶点。我们使用STRING平台构建蛋白质-蛋白质相互作用（PPI）网络，然后使用Cytoscape（3.8.2）软件可视化结果。我们还对淫羊藿的关键靶点进行了本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，然后将主要活性成分与关键靶点进行对接。最后，我们建立了SCI大鼠模型，以评估淫羊藿治疗SCI的疗效，并验证网络药理学预测的不同生物功能模块的作用。
共有133个淫羊藿靶点与SCI相关。GO术语和KEGG通路富集结果表明，淫羊藿治疗SCI的作用与炎症反应、氧化应激和PI3K/AKT信号通路显著相关。分子对接结果表明，淫羊藿的活性成分与关键靶点具有高亲和力。动物实验结果显示，淫羊藿不仅显著提高了SCI大鼠的Basso、Beattie和Bresnahan评分，还显著提高了p-PI3K/PI3K和p-AKT/AKT比值。此外，淫羊藿治疗不仅使丙二醛（MDA）显著降低，还使超氧化物歧化酶（SOD）和谷胱甘肽（GSH）均增加。然而，PI3K抑制剂LY294002成功逆转了这一现象。
淫羊藿通过抗氧化应激改善SCI大鼠的行为表现，这可能是由PI3K/AKT信号通路的激活介导的。
