Kim Myung Hee, Ryu Shi Yong, Bae Myung Ae, Choi Joon-Sig, Min Yong Ki, Kim Seong Hwan
Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon 305-600, Republic of Korea.
Food Chem Toxicol. 2008 Nov;46(11):3375-82. doi: 10.1016/j.fct.2008.08.016. Epub 2008 Aug 26.
In bone remodeling, an imbalance caused by increased bone resorption over bone formation leads to adult skeletal diseases such as osteoporosis. Therefore, the development of anti-resorptive agents has still gained more interest. In this study, using cell-based assay systems in RAW264.7 murine macrophage cells, we found that baicalein significantly inhibited the receptor activator of NF-kappaB ligand (RANKL)-induced tartrate-resistance acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in a dose-dependent manner. Interestingly, baicalein inhibited RANKL-induced activation of signaling molecules (Akt, ERK/MAP kinase and NF-kappaB) and mRNA expression of osteoclast-associated genes (TRAP, matrix metalloproteinase 9 and c-Src) and another transcription factors (c-Fos, Fra-2 and NFATc1). In addition, baicalein inhibited the bone resorptive activity of mature osteoclasts by inducing apoptosis. The inhibitory effects of baicalein on the formation of mouse bone marrow macrophage-derived osteoclasts and their bone resorptive activity were also observed. In conclusion, although further studies are needed to determine its biological efficacy and precise mechanism in bone, the present results demonstrated that baicalein has a potential to inhibit osteoclast differentiation and induce mature osteoclast apoptosis.
在骨重塑过程中，骨吸收超过骨形成所导致的失衡会引发诸如骨质疏松症等成人骨骼疾病。因此，抗吸收剂的研发仍然备受关注。在本研究中，我们利用RAW264.7小鼠巨噬细胞的细胞检测系统发现，黄芩苷能以剂量依赖的方式显著抑制核因子κB受体活化因子配体（RANKL）诱导的抗酒石酸酸性磷酸酶（TRAP）活性以及多核破骨细胞的形成。有趣的是，黄芩苷抑制RANKL诱导的信号分子（Akt、ERK/丝裂原活化蛋白激酶和核因子κB）的激活以及破骨细胞相关基因（TRAP、基质金属蛋白酶9和c-Src）和其他转录因子（c-Fos、Fra-2和活化T细胞核因子1）的mRNA表达。此外，黄芩苷通过诱导凋亡抑制成熟破骨细胞的骨吸收活性。还观察到黄芩苷对小鼠骨髓巨噬细胞来源的破骨细胞形成及其骨吸收活性具有抑制作用。总之，尽管需要进一步研究来确定其在骨中的生物学功效和精确机制，但目前的结果表明黄芩苷具有抑制破骨细胞分化和诱导成熟破骨细胞凋亡的潜力。
