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.
BMC Complement Altern Med
; 15: 280, 2015 Aug 14.
Article
em En
| MEDLINE
| ID: mdl-26271279
ABSTRACT
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, ß3-integrin, ATP6v0d2, and CtsK.CONCLUSIONS:
These findings suggest that S. hexaphylla might be useful for the development of new anti-osteoporosis agents.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
/
Reabsorção Óssea
/
Extratos Vegetais
/
Proteínas Proto-Oncogênicas c-fos
/
Magnoliopsida
/
Fatores de Transcrição NFATC
/
Fitoterapia
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article