Department of Biological Sciences, School of Science and Technology, Sunway University, 47500 Subang Jaya, Malaysia.
School of Science, Monash University Malaysia, 47500 Subang Jaya, Malaysia.
Biomed Res Int. 2019 Aug 19;2019:3126376. doi: 10.1155/2019/3126376. eCollection 2019.
In the biomedical field, there is growing interest in using human stem cell-derived neurons as models for pharmacological and toxicological screening of bioactive compounds extracted from natural products. (Tiger Milk Mushroom) is used by indigenous communities in Malaysia as a traditional medicine to treat various diseases. The sclerotium of has been reported to have medicinal properties, including various bioactivities such as neuritogenic, anti-inflammatory, and anticancer effects. This study aims to investigate the neuroprotective activities of sclerotial extracts. Human embryonic stem cell (hESC)-derived neural lineages exposed to the synthetic glucocorticoid, dexamethasone (DEX), were used as the models. Excess glucocorticoids have been shown to adversely affect fetal brain development and impair differentiation of neural progenitor cells. Screening of different sclerotial extracts and DEX on the hESC-derived neural lineages was conducted using cell viability and neurite outgrowth assays. The neuroprotective effects of sclerotial extracts against DEX were further evaluated using apoptosis assays and Western blot analysis. Hot aqueous and methanol extracts of sclerotium promoted neurite outgrowth of hESC-derived neural stem cells (NSCs) with negligible cytotoxicity. Treatment with DEX decreased viability of NSCs by inducing apoptosis. Coincubation of methanol extract with DEX attenuated the DEX-induced apoptosis and reduction in phospho-Akt (pAkt) level in NSCs. These results suggest the involvement of Akt signaling in the neuroprotection of methanol extract against DEX-induced apoptosis in NSCs. Methanol extract of sclerotium exhibited potential neuroprotective activities against DEX-induced toxicity in hESC-derived NSCs. This study thus validates the use of human stem cell-derived neural lineages as potential models for screening of natural products with neuroprotective properties.
在生物医学领域，人们越来越感兴趣地使用人类干细胞衍生的神经元作为从天然产物中提取的生物活性化合物的药理学和毒理学筛选模型。（老虎奶蘑菇）被马来西亚的土著社区用作传统药物来治疗各种疾病。已经报道称，具有药用特性，包括各种生物活性，如神经发生、抗炎和抗癌作用。本研究旨在研究 的鞘提取物的神经保护活性。用人胚胎干细胞（hESC）衍生的神经谱系暴露于合成糖皮质激素地塞米松（DEX）中作为模型。过量的糖皮质激素已被证明会对胎儿大脑发育产生不利影响，并损害神经祖细胞的分化。使用细胞活力和神经突生长测定法对不同的 鞘提取物和 DEX 进行了 hESC 衍生的神经谱系的筛选。使用凋亡测定法和 Western blot 分析进一步评估了 鞘提取物对 DEX 的神经保护作用。热的水提物和甲醇提取物促进 hESC 衍生的神经干细胞（NSCs）的神经突生长，具有极小的细胞毒性。DEX 处理通过诱导细胞凋亡降低 NSCs 的活力。与 DEX 共孵育的甲醇提取物可减轻 DEX 诱导的 NSCs 凋亡和磷酸化 Akt（pAkt）水平降低。这些结果表明 Akt 信号参与了甲醇提取物对 DEX 诱导的 NSCs 凋亡的神经保护作用。 鞘的甲醇提取物对 hESC 衍生的 NSCs 中的 DEX 诱导的毒性表现出潜在的神经保护活性。因此，本研究验证了用人干细胞衍生的神经谱系作为筛选具有神经保护特性的天然产物的潜在模型的用途。
