•Sciadopitysin inhibited RANKL-induced osteoclast formation and bone resorption.•Sciadopitysin suppressed RANKL-induced expression of TRAP, CTSK, MMP-9, c-Fos and NFATc1.•Sciadopitysin inhibited RANKL-induced NF-κB activation without altering MAPK phosphorylation.•Sciadopitysin attenuated LPS-induced bone loss in mice.Previous studies reported that sciadopitysin (Sc), a type of biflavonoids, protects reactive oxygen species (ROS)-mediated osteoblast dysfunction, but its role in osteoclastogenesis remains unclear. In this study, we observed that Sc dose-dependently suppressed RANKL-induced osteoclastogenesis and bone resorption. Our results indicated that Sc treatment strongly reduced RANKL-induced osteoclast-specific genes expression, including cathepsin K (CTSK), tartrate-resistant acid phosphatase (TRAP) and MMP-9. Furthermore, Sc apparently attenuated RANKL-increased expressions of c-Fos and NFATc1. Meanwhile, Sc also strikingly inhibited the activation of NF-κB without altering the phosphorylation of MAPKs (p38, JNK and ERK1/2). Finally, our study demonstrated that Sc administration could reverse the bone loss in LPS-induced mice model. This study suggests that Sc inhibits RANKL-induced osteoclastogenesis and bone loss by inhibiting NF-κB activation and reducing the expression of c-Fos and NFATc1. Therefore, Sc might be benefit for RANKL-mediated osteolytic bone diseases.

•HJB-1 was generated by chemical modification of a 17-hydroxy group of HJB.•HJB-1 more effectively inhibited LPS-induced TNF-α release than HJB.•HJB-1 inhibits LPS-induced mRNA expression of TNF-α, IL-1β, IL-6, COX-2 and iNOS.•HJB-1 inhibits LPS-induced NF-κB activation and MAPK phosphorylation.Jolkinolide B (JB) and 17-hydroxy-JB (HJB) are diterpenoids from plants and it has been reported that the presence of a C-17 hydroxy group in JB significantly enhances the anti-inflammatory potency of JB. In this study, two HJB derivatives HJB-1 and HJB-2 were generated by the chemical modification of a 17-hydroxy group of HJB. HJB-1 more effectively inhibited TNF-α, IL-1β and IL-6 release in LPS-stimulated mouse peritoneal macrophages. In addition, HJB-1 reduced LPS-induced mRNA expression of TNF-α, IL-1β, IL-6, COX-2 and iNOS in a concentration-dependent manner, but did not alter IL-10 mRNA expression. LPS-induced NF-κB activation and MAPK phosphorylation were also effectively inhibited by HJB-1. These results demonstrate that HJB-1 exerts anti-inflammatory effects on LPS-activated mouse peritoneal macrophages by inhibiting NF-κB activation and MAPK phosphorylation and modification of a 17-hydroxy group of HJB may enhance the anti-inflammatory potency of HJB derivatives.