ReferenceID 4109
Zanthoxylum piperitum alleviates the bone loss in osteoporosis via inhibition of RANKL-induced c-fos/NFATc1/NF-κB pathway
Phytomedicine
BACKGROUND: The fruit of Zanthoxylum piperitum (ZP) is an herbal medicine as well as a spice agent in Asia to treat carminative, stomachic, anthelmintic and degenerative diseases. Z. piperitum was reported to have anti-o
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- Reference Id
- 4109
- Evidence Id
- 20699
- Core Evidence Id
- 20699
- Source Reference Id
- 1496
- Herb2 Reference Id
- HBREF002293
- Subject Paper Key
- HERB002372_33130475
- Pubmed Id
- 33130475
- Doi
- 10.1016/j.phymed.2020.153397
- Paper Title
- Zanthoxylum piperitum alleviates the bone loss in osteoporosis via inhibition of RANKL-induced c-fos/NFATc1/NF-κB pathway
- Paper Abstract
- BACKGROUND: The fruit of Zanthoxylum piperitum (ZP) is an herbal medicine as well as a spice agent in Asia to treat carminative, stomachic, anthelmintic and degenerative diseases. Z. piperitum was reported to have anti-oxidant, anti-inflammatory, anti-osteoarthritic and osteosarcoma proliferation-control effects. PURPOSE AND STUDY DESIGN: This study was conducted to determine the anti-osteoporotic effects and mechanisms of action of ZP. METHODS: Female ICR mice underwent ovariectomies (OVX) and were orally administered ZP at 1, 10 and 100 mg/kg for 6 weeks. The femoral and tibial bones were assessed by dual-energy X-ray absorptiometry and histology to analyze the bone mineral density (BMD) and the number of osteoclasts. Raw 264.7 cells were stimulated by 100 ng/ml receptor activator of nuclear factor-kappaB ligand (RANKL) for 7 days in the presence of ZP. RANKL-induced signaling molecules were analyzed in osteoclasts. RESULTS: The levels of femoral and tibial BMD were significantly increased by ZP administration. Serum biomarkers such as osteocalcin, calcium, alkaline phosphatase and bone-specific alkaline phosphatase concentrations were markedly recovered to normal levels in ZP-treated osteoporotic mice. In addition, the number of osteoclasts in the head, trochanter and body of the femur was obviously decreased in the ZP treatment groups. Moreover, ZP treated-cells showed a reduction in the number of TRAP-positive multinuclear cells in RANKL-stimulated Raw 264.7 cells. ZP decreased the RANKL-activated NFATc1 and c-fos, transcription factors of osteoclast formation. The nuclear translocation of NF-kappaB and phosphorylation of ERK42/44 were inhibited by the ZP treatment in RANKL-induced osteoclasts. CONCLUSION: Collectively, ZP exerts its inhibitory effect against bone resorption by regulating RANKL-mediated c-fos/NFATc1/NF-kappaB in osteoclast. ZP may prove to be a therapeutic agent for osteoporosis.
- Journal
- Phytomedicine
- Publish Year
- 2021
- Experiment Subject
- mouse; raw 264.7 cells; zp treated-cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Osteosarcoma; Osteoporosis; Carminative, Stomachic, Anthelmintic And Degenerative Diseases
- Paper Title Cn
- Paper Title En
- Zanthoxylum piperitum alleviates the bone loss in osteoporosis via inhibition of RANKL-induced c-fos/NFATc1/NF-κB pathway
- Bilingual Status
- semi_complete