School of Pharmaceutical Sciences, China Medical University, No.92 Bei Er Road, He Ping District, Shenyang, 110001, China.
Molecules. 2010 Jul 5;15(7):4695-710. doi: 10.3390/molecules15074695.
Er-Xian Decoction (EXD) has been used for the treatment of osteoporosis disorders, menopausal syndrome, and other aging diseases in the Chinese traditional healthcare system. However, the targets and mechanism of action have not been clarified. This study was designed to investigate the effects and possible target proteins of EXD on osteoblastic UMR-106 cells and osteoclasts induced from RAW264.7 cells using the proteomic analysis technique. We found that EXD at a concentration of 50-200 microg/mL significantly enhanced osteoblastic UMR-106 cell proliferation, alkaline phosphatase (ALP) activity and formation of bone nodules, and decreased tartrate-resistant acid phosphatase (TRAP) activity and the bone resorption action of osteoclasts induced from RAW 264.7 cells. In EXD-treated osteoblasts, there were increases in the expression of heat-shock protein 1, high mobility group protein (Hmgb1), acidic ribosomal phosphoprotein P0, histone 2, carbonyl reductase 1, ATP synthase, aldolase A, and Rho GDP dissociation inhibitor (GDI)-alpha; and reduction in the expression of carbonic anhydrase 3, prohibitin, hemiferrin, far upstream element (FUSE)-binding protein. In EXD-treated osteoclasts, there were increases in the expression of vimentin, protein disulfide isomerase associated 3 and alpha-fetoprotein; and reduction in the expression of calnexin. These results indicated that EXD modulates bone metabolism through regulation of osteoblastic proliferation, apoptosis, and cell activation, and osteoclastic protein folding and aggregation.
二仙汤(EXD)已在中国传统医疗体系中用于治疗骨质疏松症、更年期综合征和其他衰老疾病。然而,其作用靶点和作用机制尚不清楚。本研究旨在采用蛋白质组学分析技术研究 EXD 对成骨细胞 UMR-106 和 RAW264.7 细胞诱导的破骨细胞的作用及其可能的靶蛋白。结果发现,浓度为 50-200μg/ml 的 EXD 可显著增强成骨细胞 UMR-106 细胞的增殖、碱性磷酸酶(ALP)活性和骨结节形成,降低抗酒石酸酸性磷酸酶(TRAP)活性和 RAW264.7 细胞诱导的破骨细胞的骨吸收作用。在 EXD 处理的成骨细胞中,热休克蛋白 1、高迁移率族蛋白(Hmgb1)、酸性核糖体磷蛋白 P0、组蛋白 2、羰基还原酶 1、ATP 合酶、醛缩酶 A 和 Rho GDP 解离抑制剂(GDI)-α 的表达增加;碳酸酐酶 3、抑制素、亚铁蛋白、远上游元件(FUSE)结合蛋白的表达减少。在 EXD 处理的破骨细胞中,波形蛋白、蛋白二硫键异构酶相关蛋白 3 和甲胎蛋白的表达增加;钙连蛋白的表达减少。这些结果表明,EXD 通过调节成骨细胞的增殖、凋亡和细胞激活以及破骨细胞的蛋白折叠和聚集来调节骨代谢。