Achyranthes bidentata is used as a medicinal herb prescribed for the treatment of osteoporosis in China. The anti-osteoporosis activity of the crude polysaccharide from A. bidentata , AB50, was evaluated by ovariectomized rats. The results indicated that AB50 has prominent osteoprotective effects, which was comparable to positive control. To further explore which ingredients are responsible for these effects, a novel fructan, ABW50-1 (1260 Da), was purified for the first time and characterized by chemical methods and nuclear magnetic resonance. The results revealed that ABW50-1 was composed of →2)- β -D-Fru f -(1→, →2)- β -D-Fru f -(1, 6→ and →2)- β -D-Fru f -(6→, terminated with Glu and Fru residues. Morphological analyses indicated that ABW50-1 was fragmented and contained a branched structure. Furthermore, ABW50-1 significantly increased the relative fluorescence intensity of bone mass, without side effects, in a zebrafish model of glucocorticoid-induced osteoporosis (GIOP). Thus, ABW50-1 shows potential for developing new anti-osteoporosis agents for osteoporosis therapy.
Glucocorticoid-induced osteoporosis (GIOP) represents the foremost cause of secondary osteoporosis and fragility fractures. Novel therapeutic strategies for GIOP are needed, with improved safety profiles and reduced costs compared to current options. Dendrobium officinale ( D. officinale ) is a traditional Chinese medicine that has been reported to have beneficial effects on bone metabolism. Here, we sought to investigate the impacts of D. officinale polysaccharides (DOP), the main active constituents of D. officinale , on GIOP in vivo models and dexamethasone (DEX)-treated osteoblast lineage cells. We found that low concentrations of DOP are relatively safe in vitro and in vivo , respectively. Importantly, we found that DOP treatment significantly inhibited DEX-induced osteoporosis in two in vivo models, zebrafish and mice, while boosting osteogenic differentiation of hBMSCs exposed to DEX. Futhermore, our data reveal that DOP elevates nuclear Nrf2 levels under DEX treatment, by suppressing of Nrf2 ubiquitination. Leveraging Keap1b knockout zebrafish and RNAi approach, we demonstrated that DOP disrupts the association of Nrf2/Keap1, resulting in the inhibition of Nrf2 ubiquitination. Taken together, these results illuminate that DOP stimulates osteogenesis in the presence of DEX by destabilizing the Nrf2/Keap1 interaction. These findings suggest that DOP may serve as a novel drug against osteoporosis caused by glucocorticoids.