Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Kyung Hee University, Seoul, South Korea.
Phytomedicine. 2021 Jan;80:153397. doi: 10.1016/j.phymed.2020.153397. Epub 2020 Oct 22.
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.
This study was conducted to determine the anti-osteoporotic effects and mechanisms of action of ZP.
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.
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.
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.
花椒（ZP）的果实既是亚洲的一种草药，也是一种香料，可用于治疗肠胃气胀、驱虫、消炎和退行性疾病。ZP 具有抗氧化、抗炎、抗骨关节炎和骨肉瘤增殖控制作用。
本研究旨在确定 ZP 的抗骨质疏松作用及其作用机制。
雌性 ICR 小鼠接受卵巢切除术（OVX），并经口给予 ZP 1、10 和 100mg/kg，持续 6 周。通过双能 X 射线吸收法和组织学评估股骨和胫骨的骨矿物质密度（BMD）和破骨细胞数量，分析 BMD 和破骨细胞数量。用 100ng/ml 核因子-κB 受体激活剂配体（RANKL）刺激 Raw 264.7 细胞 7 天，在存在 ZP 的情况下分析破骨细胞中的 RANKL 诱导的信号分子。
ZP 给药后股骨和胫骨 BMD 水平显著增加。ZP 治疗骨质疏松症小鼠的血清生物标志物（如骨钙素、钙、碱性磷酸酶和骨特异性碱性磷酸酶浓度）明显恢复至正常水平。此外，ZP 治疗组股骨头部、转子部和体部的破骨细胞数量明显减少。此外，ZP 处理细胞可减少 RANKL 刺激的 Raw 264.7 细胞中 TRAP 阳性多核细胞的数量。ZP 减少了 RANKL 激活的 NFATc1 和 c-fos，这是破骨细胞形成的转录因子。在 RANKL 诱导的破骨细胞中，ZP 抑制了 NF-κB 的核易位和 ERK42/44 的磷酸化。
总之，ZP 通过调节 RANKL 介导的破骨细胞中的 c-fos/NFATc1/NF-κB，发挥其抑制骨吸收的作用。ZP 可能成为治疗骨质疏松症的一种药物。
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