The isoflavone puerarin promotes generation of human iPSC-derived pre-oligodendrocytes and enhances endogenous remyelination in rodent models.

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hao Xu, Huiyuan Zhang, Nona Pop, Joe Hall, Ibrahim Shazlee, Moritz Wagner-Tsukamoto, Zhiguo Chen, Yuchun Gu, Chao Zhao, Dan Ma
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Abstract

Puerarin, a natural isoflavone, is commonly used as a Chinese herbal medicine for the treatment of various cardiovascular and neurological disorders. It has been found to be neuroprotective via TrK-PI3K/Akt pathway, which is associated with anti-inflammatory and antioxidant effects. Myelin damage in diseases such as multiple sclerosis (MS) and ischemia induces activation of endogenous oligodendrocyte progenitor cells (OPC) and subsequent remyelination by newly formed oligodendrocytes. It has been shown that human-induced pluripotent stem cells (hiPSC)-derived OPCs promote remyelination when transplanted to the brains of disease models. Here, we ask whether and how puerarin is beneficial to the generation of hiPSC-derived OPCs and oligodendrocytes, and to the endogenous remyelination in mouse demyelination model. Our results show that puerarin increases the proportion of O4+ pre-oligodendrocytes differentiated from iPSC-derived neural stem cells. In vitro, puerarin increases proliferation of rat OPCs and enhances mitochondrial activity. Treatment of puerarin at progenitor stage increases the yielding of differentiated oligodendrocytes. In rat organotypic brain slice culture, puerarin promotes both myelination and remyelination. In vivo, puerarin increases oligodendrocyte repopulation during remyelination in mouse spinal cord following lysolethicin-induced demyelination. Our findings suggest that puerarin promotes oligodendrocyte lineage progression and myelin repair, with a potential to be developed into therapeutic agent for neurological diseases associated with myelin damage.

异黄酮葛根素能促进人类iPSC衍生前橄榄枝胶质细胞的生成,并增强啮齿动物模型的内源性髓鞘再形成。
葛根素是一种天然异黄酮,是治疗各种心血管和神经系统疾病的常用中药。研究发现,葛根素能通过 TrK-PI3K/Akt 通路保护神经,而 TrK-PI3K/Akt 通路具有抗炎和抗氧化作用。多发性硬化症(MS)和缺血等疾病造成的髓鞘损伤会诱导内源性少突胶质祖细胞(OPC)的活化,随后由新形成的少突胶质细胞进行再髓鞘化。有研究表明,人类诱导多能干细胞(hiPSC)衍生的OPC移植到疾病模型的大脑后可促进髓鞘再形成。在此,我们想知道葛根素是否以及如何有益于产生hiPSC衍生的OPCs和少突胶质细胞,并有益于小鼠脱髓鞘模型中的内源性再髓鞘化。我们的研究结果表明,葛根素能提高从iPSC衍生的神经干细胞分化出的O4+前少突胶质细胞的比例。在体外,葛根素能增加大鼠 OPCs 的增殖并增强线粒体活性。在祖细胞阶段使用葛根素可提高分化少突胶质细胞的产量。在大鼠器官型脑片培养中,葛根素可促进髓鞘化和再髓鞘化。在体内,葛根素能在溶血素诱导脱髓鞘后的小鼠脊髓再髓鞘化过程中增加少突胶质细胞的再填充。我们的研究结果表明,葛根素能促进少突胶质细胞系的发展和髓鞘的修复,有望开发成治疗与髓鞘损伤相关的神经系统疾病的药物。
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来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
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