RESUMO
Bone loss induced by microgravity exposure seriously endangers the astronauts' health, but its countermeasures still have certain limitations. The study aims to find potential protective drugs for the prevention of the microgravity-induced bone loss. Here, we utilized the network pharmacology approach to discover a natural compound calycosin by constructing the compound-target interaction network and analyzing the topological characteristics of the network. Furthermore, the hind limb unloading (HLU) rats' model was conducted to investigate the potential effects of calycosin in the prevention of bone loss induced by microgravity. The results indicated that calycosin treatment group significantly increased the bone mineral density (BMD), ameliorated the microstructure of femoral trabecular bone, the thickness of cortical bone and the biomechanical properties of the bone in rats, compared that in the HLU group. The analysis of bone turnover markers in serum showed that both the bone formation markers and bone resorption markers decreased after calycosin treatment. Moreover, we found that bone remodeling-related cytokines in serum including IFN-γ, IL-6, IL-8, IL-12, IL-4, IL-10 and TNF-α were partly recovered after calycosin treatment compared with HLU group. In conclusion, calycosin partly recovered hind limb unloading-induced bone loss through the regulation of bone remodeling. These results provided the evidence that calycosin might play an important role in maintaining bone mass in HLU rats, indicating its promising application in the treatment of bone loss induced by microgravity.
RESUMO
Osteoporosis is one of the most common bone disorders that seriously affect the health and life quality of elderly individuals. Reduced osteoblast differentiation and bone formation lead to changes in bone volume and microarchitecture, leaving the bones vulnerable to fracture. Bergamottin (BM) is a natural compound derived from various citrus fruits and possesses multiple biological activities including anti-adipogenesis function. This study aimed to evaluate the effects of BM on osteoblast differentiation and its potential anti-osteoporosis capacity, as well as to explore the underlying mechanism. We demonstrated that BM, as a positive regulator for osteogenesis, significantly promoted osteoblast differentiation and bone formation. Mechanically, BM activated the Wnt/ß-catenin signaling pathway and promoted the nuclear translocation of ß-catenin. In addition, BM dramatically upregulated the expression of ß-catenin, enhanced the transcriptional activation of T cell factor 7 (TCF7), and increased the expression of Runt-related transcription factor 2 (Runx2). Taken together, this study revealed that BM enhanced osteoblast differentiation and attenuated ovariectomy (OVX)-induced bone loss, possessing the potential to be developed into a food ingredient or supplement for preventing osteoporosis.