The beneficial effect of Radix Dipsaci total saponins on bone metabolism in vitro and in vivo and the possible mechanisms of action

Niu, Youguo; Li, Y. H.; Kong, Xianghe; Zhang, R.; Sun, Yang; Li, Q.; Li, C.; Liu, L.; Wang, J.; Mei, Qibing

doi:10.1007/s00198-012-1932-y

Cited by 49 publications

(34 citation statements)

References 43 publications

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“…The anti-osteoporosis effect of RTS in vivo was systemically evaluated in a previous study by our group (20). In the present study, the effects of RTS on the osteogenic activities in MC3T3-E1 cells and the potential mechanisms of action were evaluated.…”

Section: A B C D Discussionmentioning

confidence: 91%

“…A previous study by our group demonstrated that RTS effectively inhibited osteoporosis in ovariectomized rats. Additionally, RTS has been shown to enhance MC3T3-E1 cell differentiation, potentially due to its role in increasing the expression levels of BMP-2 (20). However, the detailed molecular mechanisms of the osteogenic effects of RTS remain to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Radix Dipsaci total saponins stimulate MC3T3-E1 cell differentiation via the bone morphogenetic protein-2/MAPK/Smad-dependent Runx2 pathway

Niu

Kong

et al. 2015

Molecular Medicine Reports

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Radix Dipsaci total saponins (RTS) are primary active components of Radix Dipsaci, which is administered orally for the treatment of osteoporosis according to Chinese Medicine. RTS have also been shown to reduce the risk of bone fractures in rats. However, the detailed molecular mechanisms underlying their action remain elusive. In the present study, the ability of RTS to increase alkaline phosphatase activity, osteocalcin levels and the degree of mineralization was investigated in MC3T3‑E1 mouse osteoblast precursor cells. In addition, the associated molecular mechanism was detected. The results revealed that RTS exerted an effect on osteoblastic maturation and differentiation. Induction of differentiation by RTS was associated with an increase in the expression levels of bone morphogenetic protein‑2 (BMP‑2), phosphorylated (P)‑Smad1/5/8, P‑ERK1/2, P‑p38 and Runt‑related transcription factor 2 (Runx2). Blocking BMP‑2 expression with noggin significantly reduced the levels of osteoblastic differentiation and subsequently attenuated the expression levels of P‑Smad1/5/8, P‑ERK1/2, P‑p38 and Runx2. This indicated that RTS induced osteoblastic differentiation through BMP‑2/mitogen‑activated protein kinase/Smad1/5/8‑dependent Runx2 signaling pathways and that it may be a promising agent for enhancing bone formation.

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Section: A B C D Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Radix Dipsaci total saponins stimulate MC3T3-E1 cell differentiation via the bone morphogenetic protein-2/MAPK/Smad-dependent Runx2 pathway

Niu

Kong

et al. 2015

Molecular Medicine Reports

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“…Total flavonoid fraction of the Herb Epimedii extract prevented bone loss in OVX mice by increasing renal Ca re-absorption, stimulating the process of osteoblast formation as well as suppressing the process of osteoclastogenesis in OVX mice [ 43 ]. Radix Dipsaci extract prevented the loss of bone mass, enhanced the bone strength and prevented the deterioration of trabecular microarchitecture in OVX rats [ 44 , 45 ]. P soralea corylifolia L. extract and its main compound psoralen were reported to be able to decrease both urinary calcium excretion and serum osteocalcin in OVX rats that resulted in positive effects on maintaining BMD by increasing bone formation rate [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

In Vivo Screening for Anti-Osteoporotic Fraction from Extract of Herbal Formula Xianlinggubao in Ovariectomized Mice

Wang

Guo

et al. 2015

PLoS ONE

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Background and ObjectivesTraditional Chinese Medicine (TCM) Fufang or formula Xianlinggubao (XLGB) is a prescribed TCM drug in China registered for prevention and treatment of osteoporosis. Fufang in TCM is comprised of a group of herbal compounds contributing in group to the treatment efficacy. The present study aims to identify the bioactive fraction(s) in XLGB extract that account(s) dominantly for its osteogenic effects.MethodsThe extract of XLGB formula was separated into three fractions using chromatography, i.e., XLGB-A, XLGB-B and XLGB-C. They were administrated to 4-month old ovariectomized (OVX) mice for 6 weeks to determine which bioactive fraction(s) were more effective for preventing OVX-induced bone loss evaluated by microCT, biomechanical testing and biochemical markers. The main peaks of the key fraction were identified using reference compounds isolated from the fraction. In addition, the effects of the composite compounds in XLGB-B on osteoblasts’ proliferation and mineralization were evaluated in UMR 106 cells.ResultsXLGB-B with a yield of 13.0% from herbal Fufang XLGB was identified as the most potential one among the three fractions for prevention of OVX-induced bone loss confirmed with bone mass, bone microarchitecture, bone strength and bone turnover markers. Nine compounds in HPLC fingerprint were identified in the XLGB-B fraction, including phenylpropanoids from Herba Epimedii, terpenes from Radix Dipsaci and coumarins from Fructus Psoraleae. In addition, the identified compounds effectively promoted proliferation and/or mineralization of osteoblast-like UMR 106 cells in vitro.ConclusionXLGB-B with defined phytochemical structures was screened as the key fraction that demonstrated preventive effects on OVX-induced bone loss in mice. The present study laid down a foundation towards a new generation of herbal Fufang characterized with “less herbal materials for achieving equal treatment efficacy” in development strategy of TCM for prevention of OVX-induced osteoporosis.

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“…Biomechanical properties of femurs were measured by the three-point bending test performed using a universal material test machine (AG-1S; Shimadzu Co., Kyoto, Japan) at room temperature, as described in previous studies (18)(19)(20). Briefly, the diaphysis was placed on two supports with a span of 10 mm, while the loading pin was centered above two supports at a displacement rate of 2 mm/min, until fracture occurred.…”

Section: Excess Iron Undermined Bone Load-bearing Capacity Through Tumentioning

confidence: 99%

Excess iron undermined bone load-bearing capacity through tumor necrosis factor-α-dependent osteoclastic activation in mice

Hou²,

Zhang

et al. 2012

Biomedical Reports

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Abstract. Iron overload has been associated with bone mass loss. To elucidate the effects of excess iron on bone metabolism, an iron-overloading mouse model was established by administering iron-dextran at 250 mg/kg to female BALB/c mice. After 4 weeks, the mice were sacrificed and the biomechanical properties of the femurs were examined. The results suggested a notable decrease of the maximal bending stress and the modulus of bending elasticity in the femurs obtained from the excess iron-treated mice compared to the control mice. The levels of the serum osteocalcin, C-telopeptide of type I collagen (CTX-1) and tumor necrosis factor-α (TNF-α) were measured in order to investigate the underlying mechanism responsible for the excess iron-induced bone strength reduction. Overall, the results suggested that iron overload resulted in a marked reduction of bone load-bearing capacity through a TNF-triggered osteoclast differentiation and resorption mechanism.

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The beneficial effect of Radix Dipsaci total saponins on bone metabolism in vitro and in vivo and the possible mechanisms of action

Abstract: RTS treatment can effectively suppress the loss of bone mass induced by OVX and in vitro evidence suggests this could be through actions on both osteoblasts and osteoclasts.

Cited by 49 publications

References 43 publications

Radix Dipsaci total saponins stimulate MC3T3-E1 cell differentiation via the bone morphogenetic protein-2/MAPK/Smad-dependent Runx2 pathway

Radix Dipsaci total saponins stimulate MC3T3-E1 cell differentiation via the bone morphogenetic protein-2/MAPK/Smad-dependent Runx2 pathway

In Vivo Screening for Anti-Osteoporotic Fraction from Extract of Herbal Formula Xianlinggubao in Ovariectomized Mice

Excess iron undermined bone load-bearing capacity through tumor necrosis factor-α-dependent osteoclastic activation in mice

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