[논문]Zanthoxylum piperitum alleviates the bone loss in osteoporosis via inhibition of RANKL-induced c-fos/NFATc1/NF-κB pathway

Kim, Mi Hye; Lee, Haesu; Ha, In Jin; Yang, Woong Mo

doi:10.1016/j.phymed.2020.153397

Zanthoxylum piperitum alleviates the bone loss in osteoporosis via inhibition of RANKL-induced c-fos/NFATc1/NF-κB pathway

Phytomedicine : international journal of phytotherapy and phytopharmacology, v.80, 2021년, pp.153397 -

Kim, Mi Hye (Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University) , Lee, Haesu (Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University) , Ha, In Jin (Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Kyung Hee University) , Yang, Woong Mo (Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University)

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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-κB 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-κB 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-κB in osteoclast. ZP may prove to be a therapeutic agent for osteoporosis. Graphical abstract [DISPLAY OMISSION]

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Zanthoxylum piperitum alleviates the bone loss in osteoporosis via inhibition of RANKL-induced c-fos/NFATc1/NF-κB pathway

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Zanthoxylum piperitum alleviates the bone loss in osteoporosis via inhibition of RANKL-induced c-fos/NFATc1/NF-κB pathway

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