Osteoporosis is a common disease characterized by reduced bone mineral density and impaired bone strength and is currently one of the leading causes of fracture and morbidity among the elderly worldwide. The pathological generation of osteoclasts is an important event in the development of extensive bone resorption. Thus, the development of a drug that targets osteoclasts may be beneficial in treating osteoporosis. Accordingly, in this study, we investigated the effects of senkyunolide H (SNH), an active component extracted from ligusticum chuanxiong Hort, on osteoporosis through a series of in vivo and in vitro experiments. First, we found that SNH had a therapeutic effect in ovariectomized mice by inhibiting osteoclast formation. Then, the inhibitory effect on osteoclast differentiation was confirmed in vitro. Further western blotting analysis revealed that SNH downregulated receptor activator of nuclear factor (NF)-kappa B ligand-induced NF-kappa B signaling activation, c-Jun N-terminal kinase (JNK) in the mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) signaling pathway. These data indicated that SNH may be a potential treatment for postmenopausal osteoporosis. (C) 2020 Elsevier Inc. All rights reserved.