Baohuoside I Inhibits Osteoclastogenesis and Protects Against Ovariectomy-Induced Bone Loss

Abstract

Bone-resorbing osteoclasts are essential for skeletal remodelling, and the hyperactive formation and function of osteoclasts are common in bone metabolic diseases, especially postmenopausal osteoporosis. Therefore, regulating the osteoclast differentiation is a major therapeutic target in osteoporosis treatment. Icariin has shown potential osteoprotective effects. However, existing studies have reported limited bioavailability of icariin, and the material basis of icariin for anti-osteoporosis is attributed to its metabolites in the body. Here, we compared the effects of icariin and its metabolites (icariside I, baohuoside I, and icaritin) on osteoclastogenesis by high-content screening followed by TRAP staining and identified baohuoside I (BS) with an optimal effect. Then, we evaluated the effects of BS on osteoclast differentiation and bone resorptive activity in both in vivo and in vitro experiments. In an in vitro study, BS inhibited osteoclast formation and bone resorption function in a dose-dependent manner, and the elevated osteoclastic-related genes induced by RANKL, such as NFATc1, cathepsin K, RANK, and TRAP, were also attenuated following BS treatment. In an in vivo study, OVX-induced bone loss could be prevented by BS through interrupting the osteoclast formation and activity in mice. Furthermore, mechanistic investigation demonstrated that BS inhibited osteoclast differentiation by ameliorating the activation of the MAPK and NF-kB pathways and reducing the expression of uPAR. Our study demonstrated that baohuoside I could inhibit osteoclast differentiation and protect bone loss following ovariectomy.

Icaritin ameliorates RANKL-mediated osteoclastogenesis and ovariectomy-induced osteoporosis

“…The RNA isolation and Quantitative RT-PCR were performed as described previously [ 18 ]. Briefly, the isolated BMMs were seeded on 6-well plate at density of 2.5 × 10 3 cells/cm 2 and cultured with M-CSF (30 ng/mL).…”

“…The treatment dose of ICT is 10 mg/kg that was referred to previous study that ICT showed no toxicity for mice [ 21 ]. The sham and OVX surgery were performed according to previous description [ 18 , 20 , 22 ] and the vehicle and ICT were given by intraperitoneal injections every two day for 6 weeks. All mice were sacrificed by over dose of pentobarbital, then femurs were collected for the following experiments.…”

“…In a randomized controlled trial, Yong et al demonstrated that ICT was the main metabolites detected in serum when Epimedium prenylflavonoid extracts were consumed for 6 weeks [ 17 ]. In our previous study, ICT and icariin have similar effects on inhibiting osteoclast differentiation [ 18 ]. However, the molecular mechanism by which ICT weakens RANKL-induced osteoclast differentiation has not been completely investigated.…”

The Impact of Baohuoside I on the Metabolism of Tofacitinib in Rats

“…12 Notably, baohuoside I has been found to possess a higher inhibitory effect on osteoclast formation in RAW 264.7 cells compared to icariin, as evidenced by various studies. 13,14 The potential interaction between the coadministration of baohuoside I and tofacitinib warrants further investigation, as the impact of baohuoside I on the pharmacokinetics of tofacitinib has not been definitively established. Furthermore, the absence of any documented clinical studies examining the combined use of baohuoside I and tofacitinib necessitates additional research in this area.…”

CGK733 alleviates ovariectomy-induced bone loss through blocking RANKL-mediated Ca2+ oscillations and NF-κB/MAPK signaling pathways

“… 10 , 11 The I kappa B kinases (IKKs) are responsible for the nuclear factor-κB (NF-κB)-induced production of proto-oncogene c-Fos (c-Fos), while the mitogen-activated kinases (MAPK) pathway is responsible for the activation of Jun proteins. 12 The activating protein-1 (AP-1) complex is formed when the proteins c-Fos and Jun bind to one another. 13 NFATc1, which plays an essential part in controlling the formation of osteoclasts, is mediated by AP-1 and NF-κB.…”