Eleutherococcus sessiliflorus Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss

Abstract

The aim of this study was to evaluate the effects of root bark of Eleutherococcus sessiliflorus (ES) on osteoclast differentiation and function in vitro and in vivo. In vitro, we found that ES significantly inhibited the RANKL-induced formation of TRAP-positive multinucleated osteoclasts and osteoclastic bone resorption without cytotoxic effects. ES markedly downregulated the expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1); c-Fos; and osteoclast-related marker genes, such as TRAP, osteoclast-associated receptor (OSCAR), matrix metalloproteinase-9 (MMP-9), calcitonin receptor, cathepsin K, the 38 kDa d2 subunit of the vacuolar H+-transporting lysosomal ATPase (Atp6v0d2), dendritic cell-specific transmembrane protein (DC-STAMP), and osteoclast-stimulatory transmembrane protein (OC-STAMP). These effects were achieved by inhibiting the RANKL-mediated activation of MAPK signaling pathway proteins, including p38, ERK, and JNK. In vivo, ES attenuated OVX-induced decrease in bone volume to tissue volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and bone mineral density, but increased trabecular separation (Tb.Sp) in the femur. Collectively, our findings showed that ES inhibited RANKL-activated osteoclast differentiation in bone marrow macrophages and prevented OVX-mediated bone loss in rats. These findings suggest that ES has the potential to be used as a therapeutic agent for bone-related diseases, such as osteoporosis.

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

“…furthermore, NFATc1 knockout mice have severe osteosclerosis. 50 , 51 , 52 It regulates various osteoclast-specific genes, including Acp5 , Mmp9 , Ctsk , and Dc-stamp , through binding to MITF and c-Fos, which is critical for the formation of osteoclasts. c-Fos is an essential part of the AP-1 activator protein, which functions as a transcription factor.…”

Phytochemistry and Pharmacology of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S.Y.Hu: A Review

“…These compounds effectively reduce the production of inflammatory mediators such as NO, PGE2, TNF- α , IL-1 β , and IL-6, thereby exerting potent anti-inflammatory effects [ 9 , 16 , 83 ]. Additionally, the root barks of E. sessiliflorus have been found to inhibit osteoclast differentiation activated by RANKL in bone marrow macrophages and prevent bone loss induced by ovariectomy [ 119 ]. Moreover, E. sessiliflorus has demonstrated chondrogenic regulatory activity by enhancing the mRNA expression of markers associated with cartilage formation [ 120 ].…”

“…This compound displayed potent ABTS and DPPH radical scavenging abilities, indicating its strong antioxidant properties [50]. Additionally, HPLC analysis was conducted to determine the content of seven organic acids (caffeic acid, chlorogenic acid, neochlorogenic acid, 1,3-dicaffeoylquinic acid, isochlorogenic acid A-C (113)(114)(115)(116)(117)(118)(119) in the root at different growth stages ranging from four to eight years. The content of each organic acid increased with the age of the plant, with the 8th year showing the highest levels.…”

The Effects of Natural Product-Derived Extracts for Longitudinal Bone Growth: An Overview of In Vivo Experiments

“…E. sessiliflorus is a medicinal herb with a range of biological effects, including antiinflammatory, anti-cancer, antioxidant, and anti-obesity properties [37]. Barley (Hordeum vulgare) stands out as one of the most crucial crops globally.…”