Osteoporosis (OP) is defined as
low bone mineral density which features over activated osteoclasts (OCs) and
bone resorption. Targeting excessive OCs activity is thought to be an effective therapeutic approach for OP treatment. α-
asarone (ASA), a compound from the traditional Chinese medicinal herb Acorus tatarinowii, has been widely used as a therapeutic agent against several diseases such as
epilepsy,
cough,
bronchitis and
asthma for many years. Recently, it was reported that ASA-derived
lignins which were purified from Acorus tatarinowii root tissues effectively suppressed both RANKL-induced osteoclastogenesis and
bone resorption. Besides, a classic Chinese formulation Bajitianwan (BJTW) which consisted of root and rhizome of Acorus tatarinowii Schott also showed positive effects on
age-related bone loss. In the present study, we aimed to study the effects of ASA on osteoclastogenesis in vitro and in vivo. As illustrated by TRAP staining, ASA was capable of inhibiting RANKL-induced osteoclastogenesis in a dose-dependent manner, not only at an early-stage, but also in the late-stage. Besides, it also effectively suppressed
bone resorption of mature OCs in a pit resorption assay. The formation of
F-actin ring during osteoclastogenesis, which was important in OCs
bone-resorption, was impaired as well. Subsequent mechanism experiments exposed that ASA inhibited osteoclastogenesis related genes in a time-dependent manner through AKT, p38 and NF-κB, followed by NFATc1/c-fos signaling pathway. Notably, our in vivo study uncovered that ASA was capable of improving the bone microstructure in oestrogen-deficiency induced OP models. Thus, our current work highlighted the important role of an old drug ASA in bone metabolism especially in OCs differentiation. ASA may find its potential as a lead compound to treat excessive OCs activity-induced bone loss diseases and more structure optimization is further needed.