Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-κB and PI3K/Akt signaling pathways

摘要: Osteoclasts, the primary bone resorbing cells, are responsible for destructive diseases such as postmenopausal osteoporosis, rheumatoid arthritis, and periodontitis. Many plant-derived traditional medicines that might suppress formation and/or function of osteoclasts promising treatments osteoclast-related diseases. In this study, we investigated effects leonurine hydrochloride (LH) on receptor activator NF-κB ligand (RANKL)-induced osteoclastogenesis ovariectomy-induced loss. LH is a synthetic chemical compound based structure leonurine, which found in motherwort has been reported to exhibit phytoestrogenic activity. RAW 264.7 cells mouse marrow monocytes (BMMs), suppressed RANKL-induced actin ring dose-dependent manner. targeted resorption at an early stage. Molecular analysis demonstrated attenuated signaling by inhibiting phosphorylation degradation IκBα p65 nuclear translocation. inhibited RANK-TRAF6 association triggered RANKL binding phosphatidylinositol 3-kinase (PI3K)/Akt axis, without significantly affecting extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAPK) AP-1 pathways. RANKL-stimulated expression genes including NFATc1, tartrate resistant acid phosphatase (TRAP), cathepsin K, osteoclast-associated (OSCAR). Consistent with vitro results, administration osteoclast activity, thus preventing loss caused estrogen deficiency mice. via RANK-TRAF6, NF-κB, PI3K/Akt signaling. These data provide first evidence be therapeutic treat diseases, osteoporosis.