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首页> 外文期刊>Phytotherapy research: PTR >Inhibition of Osteoclast Differentiation by Ginsenoside Rg3 in RAW264.7 Cells via RANKL, JNK and p38 MAPK Pathways Through a Modulation of Cathepsin K: An In Silico and In Vitro Study
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Inhibition of Osteoclast Differentiation by Ginsenoside Rg3 in RAW264.7 Cells via RANKL, JNK and p38 MAPK Pathways Through a Modulation of Cathepsin K: An In Silico and In Vitro Study

机译：人参皂甙Rg3通过组织蛋白酶K的调节，通过RANKL，JNK和p38 MAPK途径抑制人参皂甙Rg3 RAW264.7细胞中的破骨细胞分化：计算机和体外研究

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Various studies have demonstrated that overexpression of cathepsin K (Cat-K) causes excessive bone loss, which ultimately leads to a variety of bone diseases including osteoporosis. Therefore, inhibition of Cat-K signifies a potential therapeutic target in osteoporosis treatment. Ginsenoside Rg3 is one of the most promising compound of Panax ginseng Meyer (P. ginseng) with numerous biological activities. Thus, in recent study the inhibitory effect of Rg3 isolated from P. ginseng was investigated in order to impede the osteoclast activity by an in silico approach followed by in vitro study validation using RAW264.7 cells through the investigation of different biological activity prediction such as absorption distribution metabolism and excretion (ADMET) properties against Cat-K protein. The docking results of our study showed that Rg3 is a non-toxic compound and may act as a drug-like molecule. Additionally, the molecular interaction of Rg3 with the active residues of Cat-K markedly describes its inhibitory effects on osteoclastogenesis. Findings of the present study exhibited that Rg3 significantly reduced receptor activator of nuclear factor kappa B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity, pit formation (actin rings), and TRAP-positive multinucleated cells development in RAW264.7 cells. Furthermore, Rg3 dose-dependently reduced the mRNA expression levels of osteoclast-specific markers such as RANK, TRAP, and Cat-K induced by RANKL through the down regulation of p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase (JNK) pathways. In conclusion, in silico docking study and in vitro validation together suggested that Rg3 inhibits osteoclastogenesis and reduces bone resorption through the inhibition of Cat-K. Therefore, Rg3 might be a useful therapeutic agent for the treatment of osteoporosis and proper bone formation. Copyright (c) 2015 John Wiley & Sons, Ltd.
机译：各种研究表明，组织蛋白酶K（Cat-K）的过度表达会导致骨量过多流失，最终导致多种骨病，包括骨质疏松症。因此，抑制Cat-K表示骨质疏松症治疗中潜在的治疗靶点。人参皂苷Rg3是人参最有前景的化合物之一，具有多种生物活性。因此，在最近的研究中，研究了从人参中分离到的Rg3的抑制作用，以便通过计算机方法阻止破骨细胞的活性，然后通过研究不同的生物学活性预测方法，例如使用RAW264.7细胞进行体外研究验证，对Cat-K蛋白的吸收分布代谢和排泄（ADMET）特性。我们研究的对接结果表明，Rg3是一种无毒化合物，可能像药物分子一样起作用。此外，Rg3与Cat-K活性残基的分子相互作用显着描述了其对破骨细胞生成的抑制作用。本研究的发现表明，Rg3在RAW264中显着降低了核因子kappa B配体（RANKL）诱导的酒石酸盐抗酸性磷酸酶（TRAP）活性，凹坑形成（肌动蛋白环）和TRAP阳性多核细胞发育的受体激活剂。 7格。此外，Rg3通过下调p38，细胞外信号调节激酶和c-Jun N端激酶，剂量依赖性地降低RANKL诱导的破骨细胞特异性标志物（如RANK，TRAP和Cat-K）的mRNA表达水平。 （JNK）途径。总之，计算机对接研究和体外验证共同表明Rg3通过抑制Cat-K抑制破骨细胞生成并减少骨吸收。因此，Rg3可能是治疗骨质疏松症和适当骨形成的有用治疗剂。版权所有（c）2015 John Wiley＆Sons，Ltd.

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