Tetrahydroxystilbene glucoside isolated from Polygonum multiflorum Thunb. demonstrates osteoblast differentiation promoting activity

Abstract

Polygonum multiflorum Thunb. is a traditional Chinese medicinal herb that has been widely used to treat age-associated diseases. Tetrahydroxystilbene glucoside (TSG), also known as 2,3,5,4-tetrahydroxystilbene-2-O-β-D-glucoside, is a major component of this herb. The present study was designed to investigate the osteogenic differentiation promoting activity of TSG in rat mesenchymal stem cells (MSCs) and in zebrafish. Preliminary experiments using MTT assay and ALP methods indicate that the high potential activity for promoting osteogenic differentiation was observed when 50% ethanol eluate was used. Further isolation and purification of TSG from the 50% ethanol eluate was performed by bioassay-guided fractionation, and its structure was confirmed using nuclear magnetic resonance and mass spectrometry analyses. In addition, the relative content of TSG with the highest potential activity in the promotion of osteogenic differentiation was identified as 14.34% by reversed-phase high performance liquid chromatography. Subsequently, the osteogenic differentiation promoting abilities of TSG in MSCs were examined. The results demonstrated that TSG promoted the alkaline phosphatase activity at concentrations of 1.56–25 µg/ml, while it increased the content of osteocalcin 7 days after treatment with 6.25–25 µg/ml in MSCs. Furthermore, experiments in zebrafish indicated that different concentrations of TSG (3.12–12.5 µg/ml) protected against further bone loss induced by 10 µmol/l dexamethasone (Dex), simulating an osteoporosis (OP) model. TSG treatment (12.5 µg/ml) in Dex-induced zebrafish significantly increased the area of nodules by 50.14% compared with the untreated model group. In conclusion, TSG, as a major component of P. multiflorum Thunb. exhibited an osteogenic promoting activity in MSCs and in zebrafish. The results provided scientific evidence to support the potential use of TSG for protecting the bone in degenerative diseases, such as OP.

Tetrahydroxy stilbene glucoside protected against diabetes‐induced osteoporosis in mice with streptozotocin‐induced hyperglycemia

“…The histological staining and quantitative microcomputed tomography (micro‐CT) analysis in this study showed the osteopreserve effects of TSG in diabetic mice, which provided in vivo evidence to support that TSG possesses bone‐sparing function in accordance with the early in vitro studies demonstrating its stimulating effects on osteogenesis in mesenchymal stem cells (Zheng et al, ) and MC3T3‐E1 cells (Zhang et al, ). Moreover, treatment of DOP mice with TSG enhanced circulating calcium level and bone calcium content, suggesting a potential application of TSG in preventing osteoporosis and managing bone health for diabetic patients.…”

Tetrahydroxystilbene Glucoside Regulates Proliferation, Differentiation, and OPG/RANKL/M-CSF Expression in MC3T3-E1 Cells via the PI3K/Akt Pathway

“…Recent studies have demonstrated that some active ingredients in these herbs have the ability to promote bone-formation [ 15 ]. TSG—the main and unique constituent of the kidney-reinforcing herb, RPMP—also exhibited a protective effect on osteoblasts [ 6 , 7 , 8 ]. However, the mechanism of TSG’s action on osteoblasts remains unclear.…”

“…Osteoblasts originate in mesenchymal stem cells. Previous studies have demonstrated that TSG could enhance the cell viability of human dental pulp stem cells [ 16 ] and rat mesenchymal stem cells [ 6 ]. Our results were consistent with the previously reported data, suggesting that TSG could protect the activity of osteoblast lineage cells.…”

“…Hence, the promotion effect of TSG on the Runx2 mRNA level benefits the elevation of Osx and Col1a1 mRNA levels. Similarly, a previous study reported that TSG increased the mRNA levels of alkaline phosphatase (ALP), collagen, and osteocalcin of MC3T3-E1 cells under oxidative stress [ 7 ], and TSG promoted the osteogenic differentiation of MSCs [ 6 ]. Thus, TSG may have the ability to increase bone mass by promoting osteoblast lineage cell differentiation and bone matrix synthesis.…”

“…Radix Polygoni Multiflori Preparata (RPMP)—the processed root of Polygonum Multiflorum Thunb—is valued for its capacity to tonify the kidney and liver and strengthen tendons and bones [ 5 ]. Tetrahydroxystilbene glucoside (2,3,5,4′-tetrahydroxystilbene-2- O -β- d -glucoside, TSG) (shown in Figure 1 ) is the unique constituent of RPMP, and has the ability to protect ostoblasts from some pathogenic factors such as dexamethasone, oxidative stress, and inflammation [ 6 , 7 , 8 ]. However, there has been little research reporting the action of TSG on osteoblast lineage cells under no pathogenic factor affection, and the signaling pathways involved in TSG’s action are still unknown.…”