Center of Excellence for Aging and Brain, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa Florida, USA.
Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
Cytotherapy. 2020 Feb;22(2):106-113. doi: 10.1016/j.jcyt.2019.12.008. Epub 2020 Jan 24.
Rhynchophylline (Rhy) effectively obstructs the expansive signaling pathways of degenerative diseases, including Alzheimer disease, Parkinson disease, epilepsy and amyotrophic lateral sclerosis, and stimulates neurogenesis. Maintenance of stemness and cell proliferation requires sophisticated intracellular environments to achieve pluripotency via specific expression of genes and proteins. We examined whether Rhy promotes this regulation in bone marrow human mesenchymal stromal cells (BM-hMSCs). Results revealed (i) Rhy modulated biological activity by regulating the mitochondria, N-methyl-D-aspartate receptor subunit, and levels of FGFβ (basic fibroblast growth factor), BDNF (brain-derived neurotrophic factor), OXTR (oxytocin receptor) and ATP (Adenosine triphosphate); (ii) Rhy altered expression level of BM-MSC proliferation/differentiation-related transcription genes; and (iii) interestingly, Rhy amplified the glycolytic flow ratio and lactate dehydrogenase activity while reducing pyruvate dehydrogenase activity, indicating a BM-hMSC metabolic shift of mitochondrial oxidative phosphorylation into aerobic glycolysis. Altogether, we demonstrated a novel mechanism of action for Rhy-induced BM-hMSC modification, which can enhance the cell transplantation approach by amplifying the metabolic activity of stem cells.
钩藤碱（Rhy）可有效阻断阿尔茨海默病、帕金森病、癫痫和肌萎缩性侧索硬化等退行性疾病的扩张信号通路，并刺激神经发生。维持干细胞特性和细胞增殖需要复杂的细胞内环境，通过特定的基因和蛋白表达来实现多能性。我们研究了 Rhy 是否能促进骨髓间充质基质细胞（BM-hMSCs）中的这种调控。结果表明：（i）Rhy 通过调节线粒体、N-甲基-D-天冬氨酸受体亚单位和 FGFβ（碱性成纤维细胞生长因子）、BDNF（脑源性神经营养因子）、OXTR（催产素受体）和 ATP（三磷酸腺苷）水平来调节生物活性；（ii）Rhy 改变了与 BM-MSC 增殖/分化相关的转录基因的表达水平；（iii）有趣的是，Rhy 增加了糖酵解流量比和乳酸脱氢酶活性，同时降低了丙酮酸脱氢酶活性，这表明 BM-hMSC 的代谢从线粒体氧化磷酸化转移到有氧糖酵解。总之，我们展示了 Rhy 诱导的 BM-hMSC 修饰的一种新作用机制，该机制可通过放大干细胞的代谢活性来增强细胞移植方法。
