Multiple neuroprotective features of Scutellaria pinnatifida-derived small molecule
Multiple neuroprotective features of Scutellaria pinnatifida-derived small molecule
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DOI：
10.1016/j.heliyon.2020.e04737
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发表时间：
2020-08-01
期刊：
影响因子：
4
通讯作者：
Morshedi, Dina
中科院分区：
文献类型：
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作者：
Parsafar, Soha;Nayeri, Zahra;Morshedi, Dina
帕金森病（Parkinson's disease，PD）是最常见的神经退行性疾病之一，病因不明。多种证据支持环境因素，无论是神经毒素或神经炎症，可以诱导帕金森症。本研究从紫茎泽兰（S. pinnatifida）的根中分离纯化了一种活性成分新黄芩素（Skullcapflavone II）。pinnatifida）。新黄芩素不仅对鱼藤酮诱导的神经毒性具有保护作用，而且在胶质细胞培养中，当用脂多糖（LPS）刺激时，它抑制炎症反应。新黄芩素具有较高的抗氧化活性，无明显毒性。此外，它还能提高细胞活力，减少早期凋亡，减少活性氧（ROS）的产生，保持神经突起的正常长度。通路富集分析（Pathway enrichment analysis，PEA）和靶点预测揭示了PD相关基因、蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络和信号通路中富集的关键蛋白，并对PD-PPI网络中的蛋白质进行了对接模拟（docking simulation，DS），发现新黄芩素可能与参与PD病理过程的关键蛋白MAPK 14、MAPK 8和CASP 3相互作用。它还阻断破坏性过程，如细胞死亡，炎症和氧化应激途径。我们的研究结果表明，新黄芩素阐明了PD相关因素的病理作用，并可能为PD治疗提供新的见解。
Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders with no precise etiology. Multiple lines of evidence support that environmental factors, either neurotoxins or neuroinflammation, can induce Parkinsonism. In this study, we purified an active compound, neobaicalein (Skullcapflavone II), from the roots of Scutellaria pinnatifida (S. pinnatifida). Neobaicalein not only had protective impacts on rotenone-induced neurotoxicity but in glial cultures, it dampened the inflammatory response when stimulated with lipopolysaccharide (LPS). Neobaicalein had high antioxidant activity without any obvious toxicity. In addition, it could raise the cell viability, decrease early apoptosis, reduce the generation of reactive oxygen species (ROS), and keep the neurite's length normal in the treated SH-SY5Y cells. Pathway enrichment analysis (PEA) and target prediction provided insights into the PD related genes, protein-protein interaction (PPI) network, and the key proteins enriched in the signaling pathways.Furthermore, docking simulation (DS) on the proteins of the PD-PPI network revealed that neobaicalein might interact with the key proteins involved in PD pathology, including MAPK14, MAPK8, and CASP3. It also blocks the destructive processes, such as cell death, inflammation, and oxidative stress pathways. Our results demonstrate that neobaicalein alleviates pathological effects of factors related to PD, and may provide new insight into PD therapy.