Ginsenoside Rg1 promotes bone marrow stromal cells proliferation via the activation of the estrogen receptor-mediated signaling pathway¹

Abstract

Aim:To investigate the possible mechanisms of ginsenoside Rg1 promoting bone marrow stromal cell (BMSC) proliferation. Methods: BMSC were isolated from bone marrow of Sprague-Dawley rats and maintained in vitro. After stimulation with 1 µmol/L ginsenoside Rg1 for the indicated time, the proliferation ability of BMSC were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and [3 H]-thymidine incorporation assays. The estrogen receptor (ER) binding activity of BMSC was determined by a specific ER antagonist and an ER binding assay. Furthermore, the influence of ginsenoside Rg1 on the expression of ERα was investigated by RT-PCR and Western blotting assays. Results: BMSC proliferation stimulated by 1 µmol/L ginsenoside Rg1 can be completely blocked by 1 µmol/L ER antagonist ICI 182, 780, or ERα-specific antagonist methylpiperidinopyrazole. Moreover, Rg1 failed to displace the specific binding of [ 3 H]17β-estradiol to BMSC cell lysates, suggesting that no direct interaction of Rg1 with the ER is needed for its estrogenic effects. In addition, 1 µmol/L Rg1 had no effects on the expression of ERα in either the mRNA or protein levels. Conclusion: Our results indicate that ERα is essential for mediating the effects of Rg1 on stimulating BMSC proliferation, which might involve the ligand/receptor-independent activation of ERα.

Ginsenoside Rg1 promotes endothelial progenitor cell migration and proliferation

“…Re and Rg1 may be a novel group of non-peptidic angiogenic agents with superior stability and may be used for the management of tissue regeneration [38] . BMSC proliferation stimulated by ginsenoside Rg1 can be completely blocked by ER antagonist ICI 182, 780, or ERα-specific antagonist methylpiperidinopyrazole, which indicates that ERα may be the key subunit that enables Rg1 to exert its action on BMSC [39] . Rg1 did not directly bind to ER or change the expression of ERα in BMSC, which was confirmed by RT-PCR and Western blotting [39] .…”

“…BMSC proliferation stimulated by ginsenoside Rg1 can be completely blocked by ER antagonist ICI 182, 780, or ERα-specific antagonist methylpiperidinopyrazole, which indicates that ERα may be the key subunit that enables Rg1 to exert its action on BMSC [39] . Rg1 did not directly bind to ER or change the expression of ERα in BMSC, which was confirmed by RT-PCR and Western blotting [39] . In this study, EPCs derived from human peripheral blood could differentiate into cells that display classical endothelial cell morphology and characteristics, such as the capacity to take up acetylated low-density lipoprotein and the expression of vWF and CD31.…”

<i>Panax notoginseng</i> Saponins Potentiate Osteogenesis of Bone Marrow Stromal Cells by Modulating Gap Junction Intercellular Communication Activities

“…Ginsenoside Rg 1 , a major component of Panax notoginseng saponins, could stimulate alkaline phosphatase activities and increase the number of osteoblasts in vitro [10]. Additionally, ginsenoside Rg 1 was found to promote the proliferation of bone marrow stromal cells [11]. In ovariectomized rats, Panax notoginseng saponins could improve bone strength and trabecular microarchitecture and promote bone mineral density [12].…”

<i>Panax Notoginseng</i> Saponins Promote Osteogenic Differentiation of Bone Marrow Stromal Cells Through the ERK and P38 MAPK Signaling Pathways

“…Panax notoginseng saponins could produce a myriad array of pharmacological responses such as antioxidative [21] and anti-inflammatory response [22]. Ginsenoside Rg1 could stimulate alkaline phosphatase activities and increase the number of osteoblasts in vitro [23] and was found to promote the proliferation of bone marrow stromal cells [24]. In addition, when incorporated into polypropylene fumarate and calcium phosphate bone cement composite, ginsenoside Rg1, could promote angiogenesis of osteonecrosed femoral head with disrupted bone blood supply [25].…”