Postmenopausal osteoporosis is a chronic population health hazard systemic metabolic disease caused by excessive bone resorption and reduced bone formation. The activity between osteoblast and osteoclast, with their mutual effects, influence the procedure of normal bone remodeling. Over-activated osteoclast differentiation and function play a crucial role in excessive bone resorption. Hence, therapy strategies targeting osteoclast activity may promote the bone mass preservation and delay the osteoporosis process. Natural compound (anethole) is emerging as potential therapeutics for various metabolic diseases. The purpose of this study is to investigate the potential effects of anethole on RANKL-induced osteoclast formation and function in vitro and in vivo. Here, in vitro TRAP staining assay was performed to investigate the inhibitory effect of anethole on osteoclast differentiation. Bone pits resorption assay revealed that osteoclast-mediated bone resorption was inhibited by anethole. At mRNA and protein levels, anethole significantly reduced the expression of osteoclast-specific genes expression in a concentration- or time-dependent manner, including NFATc1, MMP-9, DC-STAMP, c-F, TRAP, CTR, Cathepsin K, and V-ATPase d2. Furthermore, intracellular signaling transduction assay indicated that anethole inhibited osteoclast formation via blocking ERK and AKT signaling. GSK3β, the downstream signal of AKT, is simultaneously suppressed with anethole treatment. Based on ovariectomized (OVX) mice model, micro-CT and histological staining results suggested that anethole prevented estrogen deficiency-induced bone mass loss and increased osteoclast activity in vivo. In conclusion, our results show significant indications that anethole exhibits an osteoprotective effect and may be potential for the treatment of osteoporosis.

绝经后骨质疏松症是一种由于骨吸收过度和骨形成减少引起的慢性危害人群健康的全身性代谢疾病。成骨细胞和破骨细胞之间的活性，以及​​它们的相互影响，影响着正常骨重塑的过程。过度激活的破骨细胞分化和功能在过度骨吸收中起关键作用。因此，针对破骨细胞活性的治疗策略可以促进骨量保存并延缓骨质疏松症的进程。天然化合物（茴香脑）正在成为各种代谢疾病的潜在治疗剂。本研究的目的是研究茴香脑在体外和体内对 RANKL 诱导的破骨细胞形成和功能的潜在影响。在这里，体外进行TRAP染色测定以研究茴香脑对破骨细胞分化的抑制作用。骨坑吸收测定显示破骨细胞介导的骨吸收被茴香脑抑制。在 mRNA 和蛋白质水平，茴香脑以浓度或时间依赖性方式显着降低破骨细胞特异性基因的表达，包括 NFATc1、MMP-9、DC-STAMP、cF、TRAP、CTR、组织蛋白酶 K 和 V- ATP酶d2。此外，细胞内信号转导试验表明，茴香脑通过阻断 ERK 和 AKT 信号传导来抑制破骨细胞的形成。AKT 的下游信号 GSK3β 与茴香脑处理同时受到抑制。基于去卵巢（OVX）小鼠模型，在体内。总之，我们的研究结果表明茴香脑具有骨保护作用，可能具有治疗骨质疏松症的潜力。