α-Asarone Attenuates Osteoclastogenesis and Prevents Against Oestrogen-Deficiency Induced Osteoporosis

Hao Tian; Tao Jiang; Kai Yang; Ruonan Ning; Tianqi Wang; Qi Zhou; Niandong Qian; Ping Huang; Lei Guo; Min Jiang; Xiaobing Xi; Xing Xu; Lianfu Deng

doi:10.3389/fphar.2022.780590

α-Asarone Attenuates Osteoclastogenesis and Prevents Against Oestrogen-Deficiency Induced Osteoporosis

Front Pharmacol. 2022 Mar 18:13:780590. doi: 10.3389/fphar.2022.780590. eCollection 2022.

Authors

Hao Tian¹, Tao Jiang^{1

2}, Kai Yang¹, Ruonan Ning¹, Tianqi Wang¹, Qi Zhou¹, Niandong Qian¹, Ping Huang¹, Lei Guo¹, Min Jiang¹, Xiaobing Xi¹, Xing Xu¹, Lianfu Deng¹

Affiliations

¹ Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

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.

Keywords: bone loss; bone resorption; osteoclasts; osteoporosis (OP); α-asarone (ASA).