Effects of ginsenoside Rg1 on proliferation and directed differentiation of human umbilical cord mesenchymal stem cells into neural stem cells

Abstract

Objective Human umbilical cord mesenchymal stem cells (hUCMSCs) can be transformed into neural stem cells (NSCs) and still maintain immunomodulatory and antioxidant effects. Transplantation of NSCs induced by hUCMSCs would be a promising therapeutic strategy for the treatment of neurological diseases. Ginsenoside Rg1 has neuroprotective effects and influences cell proliferation and differentiation. In this study, we further evaluated the effects of ginsenoside Rg1 on the proliferation and directional differentiation of hUCMSCs into NSCs. Methods The CCK-8 assay was used to determine the optimal dose of ginsenoside Rg1 with respect to hUCMSC proliferation and differentiation. NSCs were authenticated using immunofluorescence staining and flow cytometry and were quantified in each group. RT-PCR was used to screen the signaling pathway by which ginsenoside Rg1 promoted the differentiation of hUCMSCs into NSCs. Results The optimal dose of Rg1 to promote hUCMSC proliferation and differentiation to NSCs was 10 μmol/l. Flow cytometry and immunofluorescence showed that induced NSCs expressed nestin and sex-determining region Y-box 2, with higher expression levels in the Rg1 group than that in the negative control group. RT-PCR showed that Rg1 downregulates the expression of genes involved in Wnt/β-catenin and Notch signaling pathways in the induction process. Conclusion Ginsenoside Rg1 not only promotes the proliferation and viability of hUCMSCs in the process of differentiation into NSCs but also improves the differentiation efficiency. This study provides a basis for the development of hUCMSC-derived NSCs for the treatment of nervous system diseases and for analyses of underlying biological mechanisms.

Ginsenosides can target brain-derived neurotrophic factor to improve Parkinson's disease

“…58 The neuroprotective effect of ginsenosides may be related to the MAPK, PI3K/AKT, cyclin-dependent kinase 5, BDNF/ TrkB, protein kinase A/cAMP-response element binding protein (CREB), fibroblast growth factor 2 (FGF2)/AKT, NF-κB, nod-like receptor protein1, N-methyl-D-aspartate receptor 2B/ ERK (extracellular regulated protein kinase)/CREB/BDNF, notch, Wnt/β-catenin, toll-like receptor-3 (TLR3), and TLR4 signaling pathways. 45,59,60 Ginsenosides could improve various nervous system diseases (Table 1). For instance, ginsenoside Rg1 curtailed oxi- Food & Function Review dative stress, minimized neuro-inflammation and safeguarded neurons by regulating the GSK-3β/Wnt pathway, thereby improving cognitive impairment in Alzheimer's disease (AD).…”

“…The neuroprotective effect of ginsenosides may be related to the MAPK, PI3K/AKT, cyclin-dependent kinase 5, BDNF/TrkB, protein kinase A/cAMP-response element binding protein (CREB), fibroblast growth factor 2 (FGF2)/AKT, NF-κB, nod-like receptor protein1, N -methyl- d -aspartate receptor 2B/ERK (extracellular regulated protein kinase)/CREB/BDNF, notch, Wnt/β-catenin, toll-like receptor-3 (TLR3), and TLR4 signaling pathways. 45,59,60…”

Ginsenosides on stem cells fate specification—a novel perspective

“…Ginsenoside Rg1 promotes the neural phenotype differentiation of human ADSCs by activating the expression of NSC niche components including growth associated protein-43 (GAP-43), neural cell adhesion molecule (NCAM), and synapsin-1 (SYN-1) ( Xu et al, 2014 ). In addition, ginsenoside Rg1 promotes the differentiation of human umbilical cord mesenchymal stem cells (hUCMSC) into NSCs by downregulating genes involved in the Wnt/β-catenin and Notch signaling pathways, including GSK3β, β-catenin, Notch1, and Hes1 ( Xiao et al, 2022 ). However, the transdifferentiation capability of NSCs is still doubted since the possible contamination by other tissue stem cells or embryonic stem cells in those studies.…”

Ginsenoside Rb2 Regulates Tissue Autophagy in the Ischemic Penumbra Area And Delays Bmsc Senescence by Improving The Ischemic-Hypoxic Microenvironment ​

“…One research group found that the main therapeutic effects of ginsenoside Rb1 were anti-platelet and anti-vascular remodeling activities (Xiang et al, 2020). Ginsenoside Rb1 has been focused on for the mechanism of prevention and treatment of atherosclerotic embolism (Wang et al, 2021;Xiao et al, 2022).…”