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.

中文翻译：

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钩藤碱促进干细胞自主代谢稳态

钩藤碱 (Rhy) 可有效阻断退行性疾病（包括阿尔茨海默病、帕金森病、癫痫和肌萎缩侧索硬化）的广泛信号通路，并刺激神经发生。干细胞和细胞增殖的维持需要复杂的细胞内环境，以通过基因和蛋白质的特异性表达来实现多能性。我们检查了 Rhy 是否在骨髓人类间充质基质细胞 (BM-hMSCs) 中促进这种调节。结果显示 (i) Rhy 通过调节线粒体、N-甲基-D-天冬氨酸受体亚基和 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）；(ii) Rhy 改变了 BM-MSC 增殖/分化相关转录基因的表达水平；(iii) 有趣的是，Rhy 放大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，表明线粒体氧化磷酸化的 BM-hMSC 代谢转变为有氧糖酵解。总之，我们展示了 Rhy 诱导的 BM-hMSC 修饰的新作用机制，它可以通过放大干细胞的代谢活性来增强细胞移植方法。