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Background  Natural plants, including common vegetables and fruits, have been recognized as essential sources for drug discovery and the development of new, safe, and economical medicaments.  Stauntonia hexaphylla  (Lardizabalaceae) is widely distributed in Korea, Japan, and China, and is a popular herbal supplement in Korean and Chinese folk medicine owing to its analgesic, sedative, and diuretic properties. However, the exact pharmacological effects of  S. hexaphylla  extract, particularly its effect on osteoclastogenesis, are not known.    Methods  Osteoclast differentiation and function were identified with tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assay, and the underling mechanisms were determined by real-time RT-PCR and western blot analysis.    Results   S. hexaphylla  was found to inhibit early-stage receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-mediated osteoclast differentiation in bone marrow macrophages (BMMs) without cytotoxicity and bone-resorbing activity in mature osteoclasts in a dose-dependent manner. This  S. hexaphylla -mediated blockade of osteoclastogenesis involved abrogation of the NF-κB, ERK, and c-Src-Btk-PLCγ2 calcium signal pathways. Interestingly, we found that  S. hexaphylla  down-regulated RANKL-associated c-Fos protein induction by suppressing its translation. Furthermore, ectopic overexpression of  c-Fos  and  NFATc1  rescued the inhibition of osteoclast differentiation by  S. hexaphylla . Furthermore,  S. hexaphylla  inhibited the c-Fos- and NFATc1-regulated expression of genes required for osteoclastogenesis, such as  TRAP ,  OSCAR ,  β3-integrin ,  ATP6v0d2 , and  CtsK.Conclusions  These findings suggest that  S. hexaphylla  might be useful for the development of new anti-osteoporosis agents.

bmc complementary and alternative medicine

Stauntonia hexaphylla (Lardizabalaceae) leaf methanol extract inhibits osteoclastogenesis and bone resorption activity via proteasome-mediated degradation of c-Fos protein and suppression of NFATc1 expression