Rhynchophylline promotes stem cell autonomous metabolic homeostasis

Abstract

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.

Keywords: Erythropoietin-producing hepatocellular A4; N-methyl-D-aspartate receptor; aerobic glycolysis; bone marrow human mesenchymal stromal cells; rhynchophylline.