.png){kind=icon}
.png){kind=icon}
Return
Spinosin Suppresses RANKL-induced Osteoclastogenesis and Alleviates LPS-induced Cranial Osteolysis: A Study based on Network Pharmacology and Experimental Validation
.png){kind=icon}
PRE
AI
DOI：10.2174/0109298673371731250415115235.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Aim Inflammatory osteolysis often characterizes many orthopedic diseases, with an important role played by the overactivity of osteoclasts. This research endeavoured to investigate the effects of spinosin, a potent ingredient in traditional Chinese medicine, on Lipopolysaccharide (LPS)-induced osteoclast activity and formation to alleviate osteolysis.Methods Based on the molecular structure of spinosin, network pharmacology was used to predict its primary targets and mechanisms. LPS was used to stimulate pre-osteoclasts and to simulate an inflammatory environment. The effect of spinosin on osteoclast biology was subsequently examined via morphological study, qPCR, and Western blot (WB). Moreover, LPS-induced cranial osteolysis mice were utilized, followed by micro-CT analysis, to reveal the curative effects in vivo.Results Network pharmacology and molecular docking suggested that EGFR and Akt might be the key targets for the efficacy of spinosin in inflammatory osteolysis. The results of in vitro experiments demonstrated that spinosin significantly inhibited osteoclast function and activity in the inflammatory environment, and this effect might be achieved through regulating EGFR-Akt signaling. The results of animal experiments also showed spinosin-protected mice against LPS-induced bone loss.Conclusion Spinosin can inhibit EGFR-mediated Akt phosphorylation, which in turn negatively affects downstream Nfatc1-mediated osteoclast-associated gene expression and subsequent osteoclast formation and functionality, mitigating the LPS-induced osteolysis. Our study proves that spinosin holds the promise of being an innovative drug to prevent inflammatory osteolysis.
Keywords:
Spinosin
lipopolysaccharide
inflammatory osteolysis
osteoclast
network pharmacology
rheumatoid arthritis
Journal
IF:
3.5
Papers:
7.0K
Citations:
2.1W
Organization
No organization information available
Cited Papers