[Metabolomics combined with BMP-2/Smad signaling pathway analysis elucidates ameliorative effects of total flavonoids of Epimedii Folium-bone nutritional supplement on postmenopausal osteoporosis].

Authors

Yu-Ting Qiao, Xin-Yang DU, Yu-Han Liu, Chen-Chen Dai, Ya-Xuan Li, Jing-Ran Li, Hong Kan

Published in

Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. Volume 51. Issue 13. Pages 3799-3808.

Abstract

Postmenopausal osteoporosis(PMOP) is triggered by estrogen deficiency. Insufficient estrogen lead to bone resorption exceeding bone formation, thereby causing decreased bone mass. Studies have confirmed that the total flavonoids extract from Epimedii Folium(TFE) can ameliorate osteoporosis, while the bone nutrient consisting of chondroitin sulfate(CS) combined with glucosamine hydrochloride(GLcN) exerts therapeutic effects on bone metabolism-related diseases. Since osteoporosis is fundamentally characterized by metabolic disorders, the combination of TFE-bone nutritional supplement(TG) may exert synergistic multi-target regulatory effects, thereby offering a new approach for the prevention and control of PMOP. This study systematically explored the ameliorating effects and mechanisms of TG on PMOP through in vivo and in vitro experiments combined with metabolomics technology. In vivo, a rat model of OVX was established by bilateral ovariectomy. The pharmacodynamic effects of TG on PMOP were verified based on bone histopathological staining, bone mineral density, and physiological indicators. In addition, metabolomics technology was used to quantify urine metabolites to explore the potential biomarkers of PMOP regulated by TG and the associated metabolic networks. In vitro, MC3T3-E1 cells were treated with TFE and TG to screen safe drug doses. Subsequently, osteogenic induction was performed, and the effects and mechanisms of TG on the osteogenic differentiation of MC3T3-E1 cells were studied by ALP staining, ARS staining, and Western blot analysis. Pharmacodynamic results showed that TG reduced the generation of osteoclasts and significantly restored bone mineral density and physiological indicator levels. Metabolomic results indicated that TG alleviated bone loss mainly by intervening with multiple metabolic pathways, including nicotinate and nicotinamide metabolism, histidine metabolism, pyrimidine metabolism, tryptophan metabolism, alanine, aspartate and glutamate metabolism, purine metabolism, vitamin B6 metabolism, etc. In vitro experiments confirmed that TG promoted the proliferation of osteoblasts and osteogenic differentiation via the bone morphogenetic protein-2(BMP-2)/Sma-and Mad-related protein(Smad) signaling pathway. In summary, TG can effectively ameliorate PMOP through a multi-target synergistic effect. This study provides an experimental basis and theoretical support for the clinical application of TG.

PMID:
42543370
Bibliographic data and abstract were imported from PubMed on 03 Aug 2026.

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