Castalagin exerts inhibitory effects on osteoclastogenesis through blocking a broad range of signaling pathways with low cytotoxicity
Castalagin exerts inhibitory effects on osteoclastogenesis through blocking a broad range of signaling pathways with low cytotoxicity
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Castalagin 通过阻断多种信号通路且细胞毒性低，对破骨细胞生成发挥抑制作用
DOI：
10.1002/ptr.5333
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发表时间：
2015
影响因子：
7.2
通讯作者：
T.
中科院分区：
文献类型：
--
作者：
Iwatake;M.; Sakai;E.; Okamoto;K.; Tanaka;T.; Tsukuba;T.
Castalagin是一种稀有的植物多酚，被归类为可水解的单宁。虽然它具有抗氧化、抗肿瘤和杀利什曼原虫的作用，但Castalagin对骨疾病的效用仍有待阐明。在这里，我们研究了castalagin对破骨细胞（OCL），多核骨吸收细胞分化的影响。在用核因子κ B配体受体激活剂（RANKL）刺激后，即使在1 μM时，castalagin也显著抑制骨髓源性巨噬细胞形成OCL。然而，Castalagin在50 μM的较高浓度下显示出很小的细胞毒性。Castalagin对OCL分化过程中细胞内信号传导的影响表明，Castalagin抑制RANKL刺激的主要信号传导途径的磷酸化，包括蛋白激酶B（Akt）、细胞外信号调节激酶、Jun N末端激酶、p38丝裂原活化蛋白激酶和核因子κ B α抑制剂。此外，Castalagin处理后，活化T细胞的核因子、胞质1（OCL分化的主要调节因子）和NF-κB的蛋白水平降低。因此，Castalagin通过阻断广泛的信号通路对破骨细胞生成发挥抑制作用，但具有低细胞毒性。版权所有© 2015约翰威利父子有限公司.
Castalagin is a rare plant polyphenol that is classified as a hydrolyzable tannin. Although it has antioxidant, antitumorigenic, and leishmanicidal effects, the utility of castalagin against bone diseases remain to be elucidated. Here, we investigated the effects of castalagin on the differentiation of osteoclasts (OCLs), multinucleated bone‐resorbing cells. After stimulation with receptor activator of nuclear factor kappa‐B ligand (RANKL), the formation of OCLs from bone marrow‐derived macrophages was significantly inhibited by castalagin even at 1 μM. However, castalagin displayed little cytotoxicity at a higher concentration of 50 μM. The effects of castalagin on intracellular signaling during OCL differentiation showed that castalagin suppresses RANKL‐stimulated phosphorylation of major signaling pathways including protein kinase B (Akt), extracellular signal‐regulated kinase, Jun N‐terminal kinase, p38 mitogen‐activated protein kinases, and inhibitor of nuclear factor kappa B alpha. Moreover, following castalagin treatment, the protein levels of nuclear factor of activated T‐cells, cytoplasmic 1, a master regulator for OCL differentiation, and NF‐κB were decreased. Thus, castalagin exerts inhibitory effects on osteoclastogenesis through blockage of a broad range of signaling pathways, but has low cytotoxicity. Copyright © 2015 John Wiley & Sons, Ltd.