Department of Pharmacognosy, Second Military Medical University School of Pharmacy, Shanghai, 200433, China; College of Pharmaceutical science, Zhejiang Chinese Medical University, Hangzhou, 311402, China.
School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, China.
Biochem Biophys Res Commun. 2018 Dec 2;506(4):927-931. doi: 10.1016/j.bbrc.2018.10.100. Epub 2018 Nov 2.
Rubiadin-1-methyl ether (RBM) is a natural anthraquinone compound isolated from the root of Morinda officinalis How. In our previous study, RBM was found to have inhibitory effects on the TRAP activity of osteoclasts, which means that RBM may be a candidate for therapy of bone diseases characterized by enhanced bone resorption. However, the further effect of RBM on osteoclasts and the underlying mechanism remain unclear. In the present study, we investigated the effects of RBM isolated from Morinda officinalis How. on osteoclasts derived from bone marrow macrophages (BMMs) and the underlying mechanism in vitro. RBM at the dose that did not affect the viability of cells significantly inhibited RANKL-induced osteoclastogenesis and actin ring formation of osteoclast, while RBM performed a stronger effect at the early stage. In addition, RBM downregulated the expression of osteoclast-related proteins, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene Fos (c-Fos), matrix metallopeptidase 9 (MMP-9) and cathepsin K (CtsK) as shown by Western blot. Furthermore, RBM inhibited the phosphorylation of NF-κB p65 and the degradation of IκBα as well as decreased the nuclear translocation of p65. Collectively, the results suggest that RBM inhibit osteoclastic bone resorption through blocking NF-κB pathway and may be a promising agent for the prevention and treatment of bone diseases characterized by excessive bone resorption.
染料木黄酮-1-甲醚（RBM）是从巴戟天根部分离得到的一种天然蒽醌类化合物。在我们之前的研究中，发现 RBM 对破骨细胞的 TRAP 活性具有抑制作用，这意味着 RBM 可能是治疗以增强骨吸收为特征的骨骼疾病的候选药物。然而，RBM 对破骨细胞的进一步作用及其潜在机制尚不清楚。在本研究中，我们研究了从巴戟天根部分离得到的 RBM 对骨髓巨噬细胞（BMMs）来源的破骨细胞的影响及其在体外的潜在机制。在不显著影响细胞活力的剂量下，RBM 抑制了 RANKL 诱导的破骨细胞生成和破骨细胞的肌动蛋白环形成，而 RBM 在早期阶段表现出更强的作用。此外，RBM 通过 Western blot 下调了破骨细胞相关蛋白的表达，包括活化 T 细胞核因子细胞质 1（NFATc1）、细胞癌基因 Fos（c-Fos）、基质金属蛋白酶 9（MMP-9）和组织蛋白酶 K（CtsK）。此外，RBM 抑制了 NF-κB p65 的磷酸化和 IκBα的降解，并减少了 p65 的核转位。综上所述，结果表明 RBM 通过阻断 NF-κB 途径抑制破骨细胞的骨吸收，可能是预防和治疗以过度骨吸收为特征的骨骼疾病的有前途的药物。
