Research progress on the intervention of osteoporosis by Chinese herbal monomers based on the Nrf2/NF-κB/MAPK pathway

Osteoporosis (OP) is a chronic metabolic bone disorder marked by reduced bone mass, damaged microarchitecture, and increased skeletal fragility. Its pathogenesis is complicated, and the central mechanism involves an imbalance between osteoblastic bone formation and osteoclastic bone resorption, together with several pathological processes, including excessive oxidative stress, persistent inflammatory infiltration, and abnormal apoptosis. The Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Nuclear Factor-κB (NF-κB), and Mitogen-Activated Protein Kinase (MAPK) pathways are important signaling networks controlling bone metabolism, oxidative stress, and inflammation. These pathways interact through upstream and downstream regulatory molecules. They establish complex regulatory networks through molecular interactions and crosstalk, collectively promoting the initiation and progression of OP. Traditional Chinese medicine (TCM), based on the holistic concept and "syndrome differentiation and treatment," shows promising clinical value in OP prevention and therapy because of its characteristic multi-target, multi-pathway actions and low toxicity. Extensive pharmacological evidence has confirmed that individual TCM compounds can specifically regulate the Nrf2/NF-κB pathways. By modulating redox homeostasis, inhibiting inflammatory responses, and regulating osteocyte proliferation, differentiation, and apoptosis, these compounds restore bone metabolic equilibrium and produce anti-OP effects. Current reviews mostly focus on individual signaling pathway or single herbal component, lacking systematic sorting of the cross-talk among Nrf2, NF-κB and MAPK networks. This article systematically reviews the major roles of the Nrf2, NF-κB, and MAPK pathways in osteoporosis and discusses the anti-osteoporotic mechanisms of Chinese herbal monomers, thereby providing a theoretical foundation for TCM intervention. Furthermore, it highlights syndrome differentiation and personalized treatment to overcome the limitations of basic research and clarify future clinical translation.