Qing'e Pill Rectifies Bone Homeostasis Imbalance in Diabetic Osteoporosis via the AGE/RAGE Pathway: A network pharmacology analysis and multi-omics validation

Ethnopharmacological relevance Diabetic osteoporosis (DOP), a metabolic disorder arising from diabetes mellitus, results in a hyperglycemic state that impairs bone microstructure, strength, and quality, thereby increasing the risk of fractures and complicating treatment and rehabilitation. Qing'e Pill(QEP), first recorded in the Song Dynasty's Heji Ju Fang, is renowned as an effective formula for tonifying the kidneys and strengthening bones. Its potential therapeutic mechanisms for treating DOP remain to be explored. Aim of the study This study aimed to elucidate the therapeutic mechanism of QEP, a Chinese herbal medicine compound, in the treatment of DOP by integrating network pharmacology and laboratory analyses. Materials and methods Gene targets associated with DOP were identified utilizing gene databases (GeneCards, TTD, OMIM). The active ingredients of QEP were characterized via HPLC analysis. The therapeutic potential of QEP was assessed in a rat model of DOP by monitoring blood glucose levels, employing Micro-CT imaging, and conducting histological staining. In vitro experiments were performed to confirm QEP's ability to promote bone formation. Additionally, its angiogenic potential was evaluated using scratch, migration, and tube formation assays. Results QEP was observed to stimulate osteogenesis and angiogenesis in vitro, modulate the AGE/RAGE signaling pathway, and foster anti-inflammatory osteogenesis. Micro-CT analysis demonstrated significant enhancements in bone density and microstructure following QEP treatment. Conclusion QEP enhance osteogenesis and angiogenesis via the AGE/RAGE signaling pathway, offering anti-inflammatory, hypoglycemic, and anti-osteoporotic effects. These results support the potential clinical application of QEP in managing diabetic osteoporosis.