Loganin, a major iridoid glycoside derived from Cornus officinalis, exerts strong anti‑inflammatory property. The present study aimed to investigate the underlying mechanism of loganin to reduce estrogen deficiency‑induced bone loss through a combination of network pharmacology, molecular docking and in vivo validation. First, the drug targets and structural interactions of loganin with osteoclasts on postmenopausal osteoporosis (PMOP) were predicted through network pharmacology and molecular docking. An ovariectomized (OVX) mouse model was established to experimentally validate loganin's anti‑PMOP efficacy, supported by its protective effect on bone destruction and excessive inflammatory cytokines. The top 10 core targets of loganin generated by a protein‑protein interaction network were the following: GAPDH, VEGFA, EGFR, ESR1, HRAS, SRC, FGF2, HSP90AA1, PTGS2 and IL‑2. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that loganin suppressed PMOP via mediating inflammation, bone formation, IL‑17 signaling pathway and NF‑κB signaling pathway. Molecular docking results indicated strong binding between loganin and core targets, in which the binding energy was approximately ‑5.2 and ‑7.4 kcal/mol. In vivo mouse model revealed that loganin inhibited the expression of pro‑osteoclastic markers, such as tartrate‑resistant acid phosphatase, C‑terminal telopeptide, TNF‑α and IL‑6, enhanced the secretion of bone formation markers, such as procollagen type I intact n‑terminal pro‑peptide and IL‑10, and improved bone micro‑structure (bone volume/tissue volume and trabecular number), representative of the anti‑resorptive effect mediated by loganin. In summary, the present study combined network pharmacology and molecular docking to predict the underlying mechanism of loganin against PMOP, validated by the in vivo mouse model showing that loganin attenuated OVX‑induced bone loss by inhibiting inflammation.

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