Introduction: Postmenopausal osteoporosis (PMOP) involves bone loss and fracture risk, driven by estrogen deficiency, oxidative stress, immune dysregulation, and endocrine alterations. Bushen Huoxue Decoction is used for osteoporosis, but its mechanisms in PMOP are unclear. Methods: We integrated network pharmacology, transcriptomics, machine learning, molecular docking, molecular dynamics, and absorption, distribution, metabolism, excretion, and toxicity prediction. Reactive oxygen species (ROS)-related differentially expressed genes (ROS–DEGs) from gene expression omnibus datasets were assessed by enrichment, single-sample gene set enrichment analysis (ssGSEA), feature-gene selection, diagnostic modeling, external validation, and in silico binding analyses. Results: A total of 118 compounds and 489 targets were identified. ROS-DEGs were enriched in inflammation, cell death, and bone metabolism pathways, including TNF, NF-kappa B, MAPK, Ras, and metabolic pathways. ssGSEA revealed remodeling of immune-related transcriptional signatures rather than direct changes in immune-cell composition. Integration with herbal targets highlighted ABL1 and CYP1A1 as key nodes; the combined diagnostic model outperformed single genes and was supported by external validation in GSE7429 (B-cell context). Tanshinone IIA showed the strongest predicted binding to CYP1A1. Conclusion: Bushen Huoxue Decoction may mitigate PMOP through multicomponent, multitarget modulation of ROS, immune, and bone remodeling networks. ABL1 and CYP1A1, along with Ras and metabolic pathways, represent major mechanistic axes, providing prioritized targets for experimental validation.
Li et al. (Thu,) studied this question.