Abstract：
Neural stem cells (NSCs) exhibit a remarkable capacity for self-renewal and have the potential to differentiate into various neural lineage cells, which makes them pivotal in the management of neurological disorders. Harnessing the inherent potential of endogenous NSCs for enhancing nerve repair and regeneration represents an optimal approach to addressing diseases of the nervous system. In this study, we explored the potential of a novel benzophenone derivative named Digirseophene A (DGA), which was isolated from the endophytic fungus Corydalis tomentella. Previous experiments have extensively identified and characterized DGA, revealing its unique properties. Our findings demonstrate the remarkable capability of DGA to stimulate neural stem cell proliferation, both in vitro and in vivo. Furthermore, we established a model of radiation-induced cerebellar injury to assess the effects of DGA on the distribution of different cell subpopulations within the damaged cerebellum, thereby suggesting its beneficial role in cerebellar repair. In addition, our observations on a primary NSCs model revealed that DGA significantly increased cellular oxygen consumption, indicating increased energy and metabolic demands. By utilizing various pathway inhibitors in combination with DGA, we successfully demonstrated its ability to counteract the suppressive impacts of AMPK and GSK3β inhibitors on NSC proliferation. Collectively, our research results strongly suggest that DGA, as an innovative compound, exerts its role in activating NSCs and promoting injury repair through the regulation of the AMPK/AKT/GSK3β pathway.
摘要：
神经干细胞（NSC）具有显著的自我更新能力，并具有分化为各种神经谱系细胞的潜能，这使得它们在神经系统疾病的管理中至关重要。利用内源性NSC的内在潜力来增强神经修复和再生代表了解决神经系统疾病的最佳方法。在这项研究中,我们探索了一种新的二苯甲酮衍生物的潜力，命名为二吉西芬A（DGA），从内生真菌延胡索中分离出来。以前的实验已经广泛地识别和表征了DGA，揭示其独特的属性。我们的发现证明了DGA刺激神经干细胞增殖的显着能力，在体外和体内。此外，我们建立了放射性小脑损伤模型，以评估DGA对受损小脑内不同细胞亚群分布的影响，从而表明其在小脑修复中的有益作用。此外,我们对原代神经干细胞模型的观察表明，DGA显著增加细胞耗氧量，表明能量和代谢需求增加。通过利用各种途径抑制剂与DGA的组合，我们成功证明了其抵消AMPK和GSK3β抑制剂对NSC增殖的抑制作用的能力。总的来说，我们的研究结果强烈表明DGA，作为一种创新的化合物，通过AMPK/AKT/GSK3β通路的调节发挥其激活神经干细胞和促进损伤修复的作用。
