The Potential of to Promote Bone Regeneration via Modulating Macrophage Polarization: A Network Pharmacology and Experimental Study.

(SG), a traditional Chinese medicinal herb, possesses immunomodulatory and osteoinductive properties, yet its pharmacological mechanisms in bone defect repair remain largely unexplored. This study investigates the therapeutic potential of SG through a combination of network pharmacology and experimental approaches. Active compounds were identified using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Platform, and protein interaction targets were predicted. Molecular docking and dynamics simulations assessed interactions between SG compounds and critical targets. In vitro, RAW 264.7 macrophages treated with SG-conditioned medium exhibited enhanced M2 polarization and reduced inflammation, promoting osteogenic differentiation of co-cultured MC3T3-E1 cells as evidenced by increased alkaline phosphatase activity. In vivo, scaffolds loaded with low-dose or high-dose SG (LSG/HSG) significantly improved bone regeneration in rat calvarial defects, with HSG achieving near-complete repair and mature trabeculae at 8 weeks, alongside decreased CD86 and TNF-α levels and increased IL-10 expression. Network pharmacology identified 33 shared targets related to bone regeneration and macrophage polarization, with kaempferol and beta-sitosterol demonstrating strong binding affinities to targets such as TNF, PTGS2, and CASP3. These findings highlight the potential of SG in enhancing bone defect repair and its implications for regenerative medicine.